Profiles in Practice

Hear lymphoma specialists Dr Amitkumar Mehta of the University of Alabama at Birmingham and Dr Marin Xavier of Scripps MD Anderson Cancer Center discuss patients who may be candidates for MONJUVI.

Profile in Practice #1

Transcript

DR MEHTA: I’m Dr Amitkumar Mehta. I’m joined in this video series by Dr Marin Xavier to talk about 3 different types of adult patients with refractory or relapsed diffuse large B-cell lymphoma who are ineligible for transplant. These patients may be candidates for second- or later-line targeted immunotherapy with MONJUVI plus lenalidomide. MONJUVI is a CD19-directed cytolytic monoclonal antibody.

DR XAVIER: In these videos, we’ll be talking about these hypothetical patients in terms of their treatment goals, patient and disease characteristics, and treatment history. We’ll also see some results from the L-MIND study to get a sense of why MONJUVI, a targeted immunotherapy, may be an appropriate treatment for these patients.

DR XAVIER: In this chapter, we’ll discuss the profile of a hypothetical patient with relapsed or refractory disease and comorbidities.

DR MEHTA: NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend tafasitamab-cxix (MONJUVI) in combination with lenalidomide as a preferred second-line or subsequent therapy option for DLBCL in patients who are not candidates for transplant (Category 2A).

DR MEHTA: Before we get into the details of the patient cases, let’s review the indications and usage as well as the warnings and precautions for MONJUVI.

NARRATOR: MONJUVI (tafasitamab-cxix), in combination with lenalidomide, is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant.

NARRATOR: This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial or trials.

NARRATOR: MONJUVI can cause infusion-related reactions. In the L-MIND trial, infusion-related reactions, or IRRs, occurred in 6% of the 81 patients. Eighty percent of the IRRs occurred during cycle 1 or 2. Patients should be premedicated and monitored frequently during their infusion and based on the severity of the IRRs, interrupt or discontinue MONJUVI and institute appropriate medical management.

NARRATOR: In addition, MONJUVI can cause serious or severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. Patients’ complete blood counts should be monitored prior to administration of each treatment cycle and throughout treatment. Patients with neutropenia should be monitored for signs of infection and MONJUVI should be withheld based on the severity of the adverse reaction. Consider granulocyte colony-stimulating factor administration. Refer to the lenalidomide prescribing information for dosage modifications.

NARRATOR: Fatal and serious infections, including opportunistic infections, occurred in patients during treatment with MONJUVI and following the last dose. 73% of the 81 patients developed an infection. The most frequent infections were respiratory tract infection, urinary tract infection, bronchitis, nasopharyngitis and pneumonia. Grade 3 or higher infection occurred in 30% of the 81 patients. The most frequent grade 3 or higher infection was pneumonia. Infection-related deaths were reported in 2.5% of the 81 patients. Monitor your patients for signs and symptoms of infection and manage as appropriate.

NARRATOR: Because MONJUVI may cause fetal B-cell depletion when administered to a pregnant woman, you should advise pregnant women of the potential risk to a fetus, and advise women of reproductive potential to use effective contraception during treatment with MONJUVI and for at least 3 months after the last dose. The combination of MONJUVI with lenalidomide is contraindicated in pregnant women. Refer to the lenalidomide prescribing information on use during pregnancy.

DR MEHTA: Let’s review the case of a patient with relapsed or refractory diffuse large B-cell lymphoma and additional comorbidities. This is probably someone who’s older. But this could also be a younger patient with significant comorbidities. Based on the efficacy results and safety profile demonstrated in the L-MIND study, this is a patient for whom treatment with MONJUVI and lenalidomide may be an appropriate choice.

DR MEHTA: In this hypothetical case, our patient is 75 years old, with an IPI of 2, a lower range of risk. Their ECOG score is 2, and the Ann Arbor stage is 3. They’ve also experienced hypertension, atrial fibrillation, and have a pacemaker.

DR XAVIER: In terms of treatment history, think about someone who’s had 6 cycles of frontline R-mini-CHOP and a negative PET scan, consistent with a complete response following treatment. But they’ve relapsed 2 years after treatment and are now ineligible for autologous stem cell transplant because of their comorbidities. The patient is now looking for tumor reduction.

DR XAVIER: L-MIND was an open-label, multicenter, single-arm phase 2 study of treatment with MONJUVI and lenalidomide. This study included patients with relapsed or refractory DLBCL after 1 to 3 prior systemic therapies, including a CD20-containing therapy. They were not eligible for, or refused, autologous stem cell transplant.

DR MEHTA: The primary endpoint was the best overall response rate, which was defined as the proportion of complete and partial responders. Duration of response was a select secondary endpoint. Efficacy was assessed by an Independent Review Committee using the International Working Group Response Criteria.

DR MEHTA: Patients like the one we just described were well represented in the L-MIND study. Out of the 71 patients that were evaluated for efficacy, nearly 55% of patients were older than 70 and 52% had intermediate-high to high-risk IPI scores of 3 to 5. In addition, about half of the patients had received only 1 prior therapy. Lastly, 18% of patients had atrial fibrillation.

DR MEHTA: 47% of patients were transplant-ineligible because of their age.

DR XAVIER: In the primary analysis, the best overall response rate was 55% at 1 year.

DR MEHTA: MONJUVI, in combination with lenalidomide, was granted accelerated approval based on the 1-year primary analysis of the L-MIND study. The data for the 3-year analysis of the L-MIND study has not yet been submitted to or reviewed by the FDA. The status with respect to potential inclusion of these data in the final, FDA-approved labeling has yet to be determined. This important caveat applies to all the 3-year analyses that we will discuss during this presentation.

DR XAVIER: The best overall response rate was 54% in the 3-year follow-up analysis.

DR XAVIER: In the L-MIND study, the median time to response (partial or complete) was 2 months. The median time to CR was 10.9 months and the median time to PR was 1.9 months.

DR XAVIER: This analysis is exploratory in nature. These results should be interpreted with caution due to single-arm studies not adequately characterizing time-to-event endpoints, and the small sample size, which may lead to estimates that are unstable. Please note that this important caveat applies to all the exploratory analyses that we will discuss during this presentation.

DR MEHTA: Let’s take a look at some more data from the 3-year analysis. We can examine the response rates in patients who were treated with MONJUVI and lenalidomide in the second line, and in the third line or later.

DR MEHTA: In patients who received 1 prior therapy, the best overall response rate was 63%. Of these patients, 43% achieved a complete response, and 20% achieved a partial response. In patients who received 2 or more prior therapies, the best overall response rate was 44%. 28% of these patients achieved a complete response and 17% achieved a partial response.

DR MEHTA: An exploratory analysis was conducted as a part of the 1-year analysis that measured overall response rates by subgroup.

DR XAVIER: This analysis is exploratory in nature, and L-MIND was not designed or powered to evaluate and compare multiple subgroups. These results should be interpreted with caution given the small sample size, which may lead to estimates that are unstable.

DR MEHTA: In this analysis, the overall response rate was 51% in patients over 70 and 62% in those with an IPI of 1 to 2, which is in the low-to-intermediate range.

DR XAVIER: We also saw that patients achieved a 21.7-month median duration of response in the primary analysis and a 43.9-month median duration of response in the 3-year follow-up analysis.

DR MEHTA: This swimmer plot shows the duration of response for each patient who experienced a response during the L-MIND study. Duration of response was captured from the time the initial response began for each patient. This graph represents 38 out of the 71 patients who experienced a response. Two patients started a new anti-cancer treatment immediately after a response was recorded at the end of the treatment assessment. They are still included as responders but did not record any ongoing response with MONJUVI and lenalidomide.

DR MEHTA: For patients whose response has stopped, events may include tumor progression, death, or beginning of a new anti-cancer treatment.

DR MEHTA: The initial assessment of efficacy or disease response was performed and recorded at Cycle 3, Day 1. As you can see, the majority of responding patients, which was 24 out of 38, or 63%, achieved a complete response at some point during this assessment, and nearly 50%, or 11 out of 24 of those complete responses, were observed at the first efficacy assessment (2 months).

DR MEHTA: Orange dots represent the time points when a partial response became a complete response.

DR XAVIER: The fact that 40%, or 16 out of 38 responding patients, either converted from a partial response to a complete response, or maintained an ongoing partial response, shows how important it is for patients to continue treatment with MONJUVI and lenalidomide according to the treatment schedule, as long as there is no disease progression or unacceptable toxicity.

DR XAVIER: As we discussed when reviewing the 3-year follow-up analysis, the median duration of response based on Kaplan-Meier estimates was 43.9 months, demonstrating sustained remission in patients who responded to treatment with MONJUVI + lenalidomide.

DR XAVIER: While this hypothetical patient is older, there could also be younger patients with comorbidities who are ineligible for an autologous stem cell transplant.

DR MEHTA: Yes, I’ve recently had some patients in my practice who fit this profile. Now let’s review some important safety data.

DR MEHTA: The most common adverse reactions in 10% or more of patients are summarized here. The most common hematological adverse reactions were neutropenia, anemia, and thrombocytopenia. 49% of patients had grade 3 or 4 neutropenia, 17% had grade 3 or 4 thrombocytopenia, and 12% of patients had grade 3 or 4 febrile neutropenia.

DR XAVIER: This table summarizes other clinically relevant adverse reactions that occurred in less than 10% of patients in L-MIND. Some adverse reactions to be aware of include lymphopenia (6%), infusion-related reactions (6%), sepsis (4.9%), weight decreased (4.9%), arthralgia (9%), pain in extremity (9%), headache (9%), paresthesia (7%), dysgeusia (6%), nasal congestion (4.9%), and erythema (4.9%).

DR XAVIER: For details about additional clinically relevant adverse reactions, please refer to the full Prescribing Information.

DR MEHTA: In addition, select laboratory abnormalities that worsened from baseline in more than 20% of patients receiving MONJUVI are listed here. Noteworthy laboratory abnormalities include the following: glucose increased in 49% of patients, and grade 3/4 in 5% of patients; gamma glutamyl transferase increased in 34% of patients, and grade 3/4 in 5% of patients; urate increased in 20% of patients, and grade 3/4 in 7% of patients; phosphate decreased in 20% of patients, and grade 3/4 in 5% of patients; and activated partial thromboplastin time increased in 46% of patients, and grade 3/4 in 4.1% of patients.

DR MEHTA: For details about additional laboratory abnormalities, please refer to the full Prescribing Information.

DR XAVIER: Let’s take a look at hematologic toxicity management and dosing modifications in L-MIND. 44% of patients received concomitant granulocyte-colony stimulating factor. 46% of patients had at least 1 dose reduction of lenalidomide. 78% of patients were able to receive a lenalidomide dose of at least 20 milligrams per day over the duration of their treatment.

DR XAVIER: Permanent discontinuation of MONJUVI or lenalidomide due to an adverse reaction occurred in 25% of patients and permanent discontinuation of MONJUVI due to an adverse reaction occurred in 15%.

DR XAVIER: Dosage interruptions of MONJUVI or lenalidomide due to an adverse reaction occurred in 69% of patients and dosage interruption of MONJUVI due to an adverse reaction occurred in 65%.

DR XAVIER: MONJUVI balances efficacy with tolerability in patients with relapsed or refractory disease and comorbidities. To learn more about other patients in whom MONJUVI may be an option, please watch the other videos in this series and visit our website at MonjuviHCP.com. Now we will share the Important Safety Information about MONJUVI.

Important Safety Information

NARRATOR: Contraindications

NARRATOR: None.

Warnings and Precautions

Infusion-Related Reactions

NARRATOR: MONJUVI can cause infusion-related reactions (IRRs). In L-MIND, infusion-related reactions occurred in 6% of the 81 patients. Eighty percent of infusion-related reactions occurred during cycle 1 or 2. Signs and symptoms included fever, chills, rash, flushing, dyspnea, and hypertension. These reactions were managed with temporary interruption of the infusion and/or with supportive medication. Premedicate patients prior to starting MONJUVI infusion. Monitor patients frequently during infusion. Based on the severity of the infusion-related reaction, interrupt or discontinue MONJUVI. Institute appropriate medical management.

Myelosuppression

NARRATOR: MONJUVI can cause serious or severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. In L-MIND, Grade 3 neutropenia occurred in 25% of patients, thrombocytopenia in 12%, and anemia in 7%. Grade 4 neutropenia occurred in 25% and thrombocytopenia in 6%. Neutropenia led to treatment discontinuation in 3.7% of patients.

NARRATOR: Monitor complete blood counts (CBC) prior to administration of each treatment cycle and throughout treatment. Monitor patients with neutropenia for signs of infection. Consider granulocyte colony-stimulating factor (G-CSF) administration. Withhold MONJUVI based on the severity of the adverse reaction. Refer to the lenalidomide prescribing information for dosage modifications.

Infections

NARRATOR: Fatal and serious infections, including opportunistic infections, occurred in patients during treatment with MONJUVI and following the last dose.

NARRATOR: In L-MIND, 73% of the 81 patients developed an infection. The most frequent infections were respiratory tract infection (24%), urinary tract infection (17%), bronchitis (16%), nasopharyngitis (10%) and pneumonia (10%). Grade 3 or higher infection occurred in 30% of the 81 patients. The most frequent grade 3 or higher infection was pneumonia (7%). Infection-related deaths were reported in 2.5% of the 81 patients.

NARRATOR: Monitor patients for signs and symptoms of infection and manage infections as appropriate.

Embryo-Fetal Toxicity

NARRATOR: Based on its mechanism of action, MONJUVI may cause fetal B-cell depletion when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise women of reproductive potential to use effective contraception during treatment with MONJUVI and for at least 3 months after the last dose.

NARRATOR: MONJUVI is initially administered in combination with lenalidomide. The combination of MONJUVI with lenalidomide is contraindicated in pregnant women because lenalidomide can cause birth defects and death of the unborn child. Refer to the lenalidomide prescribing information on use during pregnancy.

Adverse Reactions

NARRATOR: Serious adverse reactions occurred in 52% of patients who received MONJUVI. Serious adverse reactions in ≥6% of patients included infections (26%), including pneumonia (7%), and febrile neutropenia (6%). Fatal adverse reactions occurred in 5% of patients who received MONJUVI, including cerebrovascular accident (1.2%), respiratory failure (1.2%), progressive multifocal leukoencephalopathy (1.2%) and sudden death (1.2%).

NARRATOR: Permanent discontinuation of MONJUVI or lenalidomide due to an adverse reaction occurred in 25% of patients and permanent discontinuation of MONJUVI due to an adverse reaction occurred in 15%. The most frequent adverse reactions which resulted in permanent discontinuation of MONJUVI were infections (5%), nervous system disorders (2.5%), respiratory, thoracic, and mediastinal disorders (2.5%).

NARRATOR: Dosage interruptions of MONJUVI or lenalidomide due to an adverse reaction occurred in 69% of patients and dosage interruption of MONJUVI due to an adverse reaction occurred in 65%. The most frequent adverse reactions which required a dosage interruption of MONJUVI were blood and lymphatic system disorders (41%), and infections (27%).

NARRATOR: The most common adverse reactions (≥20%) were neutropenia (51%), fatigue (38%), anemia (36%), diarrhea (36%), thrombocytopenia (31%), cough (26%), pyrexia (24%), peripheral edema (24%), respiratory tract infection (24%), and decreased appetite (22%).

NARRATOR: You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to MORPHOSYS US INC. at (844) 667-1992.

NARRATOR: Please see the full Prescribing Information for additional Important Safety Information available at MONJUVI.com.

DR MEHTA: Following an assessment of clinical factors, consider targeted immunotherapy with MONJUVI as an option for the second-line treatment of DLBCL in transplant-ineligible patients who want to continue treatment with their current care team, receive outpatient treatment, access treatment in a local office or clinic, and/or receive treatment in a timely manner.

DR XAVIER: On behalf of Dr Mehta, I’m Dr Xavier. Thank you for joining us for this presentation. Be sure to visit MonjuviHCP.com to learn more about treatment with MONJUVI and lenalidomide.

Profile in Practice #2

Transcript

DR MEHTA: I’m Dr Amitkumar Mehta. I’m joined in this video series by Dr Marin Xavier to talk about 3 different types of adult patients with refractory or relapsed diffuse large B-cell lymphoma who are ineligible for transplant. These patients may be candidates for second- or later-line targeted immunotherapy with MONJUVI plus lenalidomide. MONJUVI is a CD19-directed cytolytic monoclonal antibody.

DR XAVIER: In these videos, we’ll be talking about these hypothetical patients in terms of their treatment goals, patient and disease characteristics, and treatment history. We’ll also see some results from the L-MIND study to get a sense of why MONJUVI, a targeted immunotherapy, may be an appropriate treatment for these patients.

DR XAVIER: In this chapter, we’ll be talking about a hypothetical patient with chemorefractory disease.

DR MEHTA: NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend tafasitamab-cxix (MONJUVI) in combination with lenalidomide as a preferred second-line or subsequent therapy option for DLBCL in patients who are not candidates for transplant (Category 2A).

DR MEHTA: Before we get into the details of the patient cases, let’s review the indications and usage as well as the warnings and precautions for MONJUVI.

NARRATOR: MONJUVI (tafasitamab-cxix), in combination with lenalidomide, is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant.

NARRATOR: This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial or trials.

NARRATOR: MONJUVI can cause infusion-related reactions. In the L-MIND trial, infusion-related reactions, or IRRs, occurred in 6% of the 81 patients. Eighty percent of the IRRs occurred during cycle 1 or 2. Patients should be premedicated and monitored frequently during their infusion and based on the severity of the IRRs, interrupt or discontinue MONJUVI and institute appropriate medical management.

NARRATOR: In addition, MONJUVI can cause serious or severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. Patients’ complete blood counts should be monitored prior to administration of each treatment cycle and throughout treatment. Patients with neutropenia should be monitored for signs of infection and MONJUVI should be withheld based on the severity of the adverse reaction. Consider granulocyte colony-stimulating factor administration. Refer to the lenalidomide prescribing information for dosage modifications.

NARRATOR: Fatal and serious infections, including opportunistic infections, occurred in patients during treatment with MONJUVI and following the last dose. 73% of the 81 patients developed an infection. The most frequent infections were respiratory tract infection, urinary tract infection, bronchitis, nasopharyngitis and pneumonia. Grade 3 or higher infection occurred in 30% of the 81 patients. The most frequent grade 3 or higher infection was pneumonia. Infection-related deaths were reported in 2.5% of the 81 patients. Monitor your patients for signs and symptoms of infection and manage as appropriate.

NARRATOR: Because MONJUVI may cause fetal B-cell depletion when administered to a pregnant woman, you should advise pregnant women of the potential risk to a fetus, and advise women of reproductive potential to use effective contraception during treatment with MONJUVI and for at least 3 months after the last dose. The combination of MONJUVI with lenalidomide is contraindicated in pregnant women. Refer to the lenalidomide prescribing information on use during pregnancy.

DR XAVIER: Let’s take a look at a patient who is considered chemorefractory, meaning that salvage chemotherapy failed to induce a response. The initial goal was a stem cell transplant. However, salvage high-dose chemotherapy was ineffective and the patient was considered transplant-ineligible. Dr Mehta and I will review why MONJUVI may be a treatment option to consider in this case.

DR XAVIER: This hypothetical patient is 68 years old and has an IPI of 3, which is in the intermediate-high to high risk range, and is at Ann Arbor stage 3. This is a patient who’s minimally restricted by their disease—the ECOG score is 1, but they also have an elevated LDH. They’ve also experienced hypothyroidism. Additional nonclinical considerations are that the patient lives in a rural area and wants to stay local to receive outpatient treatment. Financial considerations are important to this patient.

DR MEHTA: As you mentioned, Dr Xavier, salvage chemotherapy failed to induce a response in this patient. But there are also other complications in terms of treatment history.

DR MEHTA: This hypothetical patient achieved a complete response following R-CHOP, but progressed 6 months after completion of first-line therapy, and has active, bulky disease. Salvage chemotherapy failed to induce a response in this chemorefractory patient, making them ineligible for autologous stem-cell therapy. Their performance status declined to ECOG 2 following chemotherapy.

DR XAVIER: Let’s take a look at the study population in L-MIND, an open-label, multicenter, single-arm phase 2 study of treatment with MONJUVI and lenalidomide. You’ll recognize many of the patient characteristics we just mentioned.

DR XAVIER: L-MIND included patients with relapsed or refractory diffuse large B-cell lymphoma after 1 to 3 prior systemic therapies, including a CD20-containing therapy. They were not eligible for, or refused, autologous stem cell transplant.

DR MEHTA: The primary endpoint was the best overall response rate, which was defined as the proportion of complete and partial responders. Duration of response was a select secondary endpoint. Efficacy was assessed by an Independent Review Committee using the International Working Group Response Criteria.

DR MEHTA: Patients like the one we just described were well represented in the L-MIND study. Out of the 71 patients that were evaluated for efficacy, 27% of patients were refractory to salvage chemotherapy or showed no response to salvage chemo. 52% had IPI scores of 3 to 5, which are in the intermediate-high to high-risk range. 45% were refractory to their last prior therapy, and 24% experienced relapse or progression within 12 months of their first DLBCL diagnosis.

DR MEHTA: The study included a sizable proportion of patients with characteristics considered difficult-to-treat. And the data that follows shows that these patients may be appropriate candidates for treatment with MONJUVI.

DR XAVIER: In the primary analysis, the best overall response rate was 55% at 1 year.

DR MEHTA: MONJUVI, in combination with lenalidomide, was granted accelerated approval based on the 1-year primary analysis of the L-MIND study. The data for the 3-year analysis of the L-MIND study has not yet been submitted to or reviewed by the FDA. The status with respect to potential inclusion of these data in the final, FDA-approved labeling has yet to be determined. This important caveat applies to all the 3-year analyses that we will discuss during this presentation.

DR XAVIER: The best overall response rate was 54% in the 3-year follow-up analysis.

DR XAVIER: In the L-MIND study, the median time to response (partial or complete) was 2 months. The median time to CR was 10.9 months and the median time to PR was 1.9 months.

DR XAVIER: This analysis is exploratory in nature. These results should be interpreted with caution due to single-arm studies not adequately characterizing time-to-event endpoints, and the small sample size, which may lead to estimates that are unstable. Please note that this important caveat applies to all the exploratory analyses that we will discuss during this presentation.

DR MEHTA: Let’s take a look at some more data from the 3-year analysis. We can examine the response rates in patients who were treated with MONJUVI and lenalidomide in the second line, and in the third line or later.

DR MEHTA: In patients who received 1 prior therapy, the best overall response rate was 63%. Of these patients, 43% achieved a complete response, and 20% achieved a partial response. In patients who received 2 or more prior therapies, the best overall response rate was 44%. 28% of these patients achieved a complete response and 17% achieved a partial response.

DR MEHTA: An exploratory analysis was conducted as a part of the 1-year analysis that measured overall response rates by subgroup.

DR XAVIER: This analysis is exploratory in nature, and L-MIND was not designed or powered to evaluate and compare multiple subgroups. These results should be interpreted with caution given the small sample size, which may lead to estimates that are unstable.

DR MEHTA: In this analysis, the overall response rate was 53% for patients with elevated LDH, 56% for patients with Ann Arbor stage 3 to 4 disease, and 49% for patients with an intermediate-high to high-risk IPI score in the 3 to 5 range.

DR XAVIER: We also saw that patients achieved a 21.7-month median duration of response in the primary analysis and a 43.9-month median duration of response in the 3-year follow-up analysis.

DR MEHTA: This swimmer plot shows the duration of response for each patient who experienced a response during the L-MIND study. Duration of response was captured from the time the initial response began for each patient. This graph represents 38 out of the 71 patients who experienced a response. Two patients started a new anti-cancer treatment immediately after a response was recorded at the end of the treatment assessment. They are still included as responders but did not record any ongoing response with MONJUVI and lenalidomide.

DR MEHTA: For patients whose response has stopped, events may include tumor progression, death, or beginning of a new anti-cancer treatment.

DR MEHTA: The initial assessment of efficacy or disease response was performed and recorded at Cycle 3, Day 1. As you can see, the majority of responding patients, which was 24 out of 38, or 63%, achieved a complete response at some point during this assessment, and nearly 50%, or 11 out of 24 of those complete responses, were observed at the first efficacy assessment (2 months).

DR MEHTA: Orange dots represent the time points when a partial response became a complete response.

DR XAVIER: The fact that 40%, or 16 out of 38 responding patients, either converted from a partial response to a complete response, or maintained an ongoing partial response, shows how important it is for patients to continue treatment with MONJUVI and lenalidomide according to the treatment schedule, as long as there is no disease progression or unacceptable toxicity.

DR XAVIER: As we discussed when reviewing the 3-year follow-up analysis, the median duration of response based on Kaplan-Meier estimates was 43.9 months, demonstrating sustained remission in patients who responded to treatment with MONJUVI + lenalidomide.

DR XAVIER: MONJUVI is targeted immunotherapy for adult patients with DLBCL who have received at least 1 prior therapy, in combination with lenalidomide. MONJUVI is a potential treatment option for patients who are transplant-ineligible, and who did not respond to salvage chemotherapy. Now let’s review some important safety data.

DR MEHTA: The most common adverse reactions in 10% or more of patients are summarized here. The most common hematological adverse reactions were neutropenia, anemia, and thrombocytopenia. 49% of patients had grade 3 or 4 neutropenia, 17% had grade 3 or 4 thrombocytopenia, and 12% of patients had grade 3 or 4 febrile neutropenia.

DR XAVIER: This table summarizes other clinically relevant adverse reactions that occurred in less than 10% of patients in L-MIND. Some adverse reactions to be aware of include lymphopenia (6%), infusion-related reactions (6%), sepsis (4.9%), weight decreased (4.9%), arthralgia (9%), pain in extremity (9%), headache (9%), paresthesia (7%), dysgeusia (6%), nasal congestion (4.9%), and erythema (4.9%).

DR XAVIER: For details about additional clinically relevant adverse reactions, please refer to the full Prescribing Information.

DR MEHTA: In addition, select laboratory abnormalities that worsened from baseline in more than 20% of patients receiving MONJUVI are listed here. Noteworthy laboratory abnormalities include the following: glucose increased in 49% of patients, and grade 3/4 in 5% of patients; gamma glutamyl transferase increased in 34% of patients, and grade 3/4 in 5% of patients; urate increased in 20% of patients, and grade 3/4 in 7% of patients; phosphate decreased in 20% of patients, and grade 3/4 in 5% of patients; and activated partial thromboplastin time increased in 46% of patients, and grade 3/4 in 4.1% of patients.

DR MEHTA: For details about additional laboratory abnormalities, please refer to the full Prescribing Information.

DR XAVIER: Let’s take a look at hematologic toxicity management and dosing modifications in L-MIND. 44% of patients received concomitant granulocyte-colony stimulating factor. 46% of patients had at least 1 dose reduction of lenalidomide. 78% of patients were able to receive a lenalidomide dose of at least 20 milligrams per day over the duration of their treatment.

DR XAVIER: Permanent discontinuation of MONJUVI or lenalidomide due to an adverse reaction occurred in 25% of patients and permanent discontinuation of MONJUVI due to an adverse reaction occurred in 15%.

DR XAVIER: Dosage interruptions of MONJUVI or lenalidomide due to an adverse reaction occurred in 69% of patients and dosage interruption of MONJUVI due to an adverse reaction occurred in 65%.

DR XAVIER: MONJUVI offers a balance of efficacy and tolerability for patients with chemorefractory disease. To learn more about other patients in whom MONJUVI may be an option, please watch the other videos in this series and visit our website at MonjuviHCP.com. Now we will share the Important Safety Information about MONJUVI.

Important Safety Information

NARRATOR: Contraindications

NARRATOR: None.

Warnings and Precautions

Infusion-Related Reactions

NARRATOR: MONJUVI can cause infusion-related reactions (IRRs). In L-MIND, infusion-related reactions occurred in 6% of the 81 patients. Eighty percent of infusion-related reactions occurred during cycle 1 or 2. Signs and symptoms included fever, chills, rash, flushing, dyspnea, and hypertension. These reactions were managed with temporary interruption of the infusion and/or with supportive medication. Premedicate patients prior to starting MONJUVI infusion. Monitor patients frequently during infusion. Based on the severity of the infusion-related reaction, interrupt or discontinue MONJUVI. Institute appropriate medical management.

Myelosuppression

NARRATOR: MONJUVI can cause serious or severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. In L-MIND, Grade 3 neutropenia occurred in 25% of patients, thrombocytopenia in 12%, and anemia in 7%. Grade 4 neutropenia occurred in 25% and thrombocytopenia in 6%. Neutropenia led to treatment discontinuation in 3.7% of patients.

NARRATOR: Monitor complete blood counts (CBC) prior to administration of each treatment cycle and throughout treatment. Monitor patients with neutropenia for signs of infection. Consider granulocyte colony-stimulating factor (G-CSF) administration. Withhold MONJUVI based on the severity of the adverse reaction. Refer to the lenalidomide prescribing information for dosage modifications.

Infections

NARRATOR: Fatal and serious infections, including opportunistic infections, occurred in patients during treatment with MONJUVI and following the last dose.

NARRATOR: In L-MIND, 73% of the 81 patients developed an infection. The most frequent infections were respiratory tract infection (24%), urinary tract infection (17%), bronchitis (16%), nasopharyngitis (10%) and pneumonia (10%). Grade 3 or higher infection occurred in 30% of the 81 patients. The most frequent grade 3 or higher infection was pneumonia (7%). Infection-related deaths were reported in 2.5% of the 81 patients.

NARRATOR: Monitor patients for signs and symptoms of infection and manage infections as appropriate.

Embryo-Fetal Toxicity

NARRATOR: Based on its mechanism of action, MONJUVI may cause fetal B-cell depletion when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise women of reproductive potential to use effective contraception during treatment with MONJUVI and for at least 3 months after the last dose.

NARRATOR: MONJUVI is initially administered in combination with lenalidomide. The combination of MONJUVI with lenalidomide is contraindicated in pregnant women because lenalidomide can cause birth defects and death of the unborn child. Refer to the lenalidomide prescribing information on use during pregnancy.

Adverse Reactions

NARRATOR: Serious adverse reactions occurred in 52% of patients who received MONJUVI. Serious adverse reactions in ≥6% of patients included infections (26%), including pneumonia (7%), and febrile neutropenia (6%). Fatal adverse reactions occurred in 5% of patients who received MONJUVI, including cerebrovascular accident (1.2%), respiratory failure (1.2%), progressive multifocal leukoencephalopathy (1.2%) and sudden death (1.2%).

NARRATOR: Permanent discontinuation of MONJUVI or lenalidomide due to an adverse reaction occurred in 25% of patients and permanent discontinuation of MONJUVI due to an adverse reaction occurred in 15%. The most frequent adverse reactions which resulted in permanent discontinuation of MONJUVI were infections (5%), nervous system disorders (2.5%), respiratory, thoracic, and mediastinal disorders (2.5%).

NARRATOR: Dosage interruptions of MONJUVI or lenalidomide due to an adverse reaction occurred in 69% of patients and dosage interruption of MONJUVI due to an adverse reaction occurred in 65%. The most frequent adverse reactions which required a dosage interruption of MONJUVI were blood and lymphatic system disorders (41%), and infections (27%).

NARRATOR: The most common adverse reactions (≥20%) were neutropenia (51%), fatigue (38%), anemia (36%), diarrhea (36%), thrombocytopenia (31%), cough (26%), pyrexia (24%), peripheral edema (24%), respiratory tract infection (24%), and decreased appetite (22%).

NARRATOR: You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to MORPHOSYS US INC. at (844) 667-1992.

NARRATOR: Please see the full Prescribing Information for additional Important Safety Information available at MONJUVI.com.

DR MEHTA: Following an assessment of clinical factors, consider targeted immunotherapy with MONJUVI as an option for the second-line treatment of DLBCL in transplant-ineligible patients who want to continue treatment with their current care team, receive outpatient treatment, access treatment in a local office or clinic, and/or receive treatment in a timely manner.

DR XAVIER: On behalf of Dr Mehta, I’m Dr Xavier. Thank you for joining us for this presentation. Be sure to visit MonjuviHCP.com to learn more about treatment with MONJUVI and lenalidomide.

Profile in Practice #3

Transcript

DR MEHTA: I’m Dr Amitkumar Mehta. I’m joined in this video series by Dr Marin Xavier to talk about 3 different types of adult patients with refractory or relapsed diffuse large B-cell lymphoma who are ineligible for transplant. These patients may be candidates for second- or later-line targeted immunotherapy with MONJUVI plus lenalidomide. MONJUVI is a CD19-directed cytolytic monoclonal antibody.

DR XAVIER: In these videos, we’ll be talking about these hypothetical patients in terms of their treatment goals, patient and disease characteristics, and treatment history. We’ll also see some results from the L-MIND study to get a sense of why MONJUVI, a targeted immunotherapy, may be an appropriate treatment for these patients.

DR XAVIER: In this chapter, we’ll be reviewing the hypothetical case of a patient whose disease progressed within 12 months of their initial diagnosis and who wants to receive treatment in their local area from their current care team.

DR MEHTA: NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend tafasitamab-cxix (MONJUVI) in combination with lenalidomide as a preferred second-line or subsequent therapy option for DLBCL in patients who are not candidates for transplant (Category 2A).

DR MEHTA: Before we get into the details of the patient cases, let’s review the indications and usage as well as the warnings and precautions for MONJUVI.

NARRATOR: MONJUVI (tafasitamab-cxix), in combination with lenalidomide, is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant.

NARRATOR: This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial or trials.

NARRATOR: MONJUVI can cause infusion-related reactions. In the L-MIND trial, infusion-related reactions, or IRRs, occurred in 6% of the 81 patients. Eighty percent of the IRRs occurred during cycle 1 or 2. Patients should be premedicated and monitored frequently during their infusion and based on the severity of the IRRs, interrupt or discontinue MONJUVI and institute appropriate medical management.

NARRATOR: In addition, MONJUVI can cause serious or severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. Patients’ complete blood counts should be monitored prior to administration of each treatment cycle and throughout treatment. Patients with neutropenia should be monitored for signs of infection and MONJUVI should be withheld based on the severity of the adverse reaction. Consider granulocyte colony-stimulating factor administration. Refer to the lenalidomide prescribing information for dosage modifications.

NARRATOR: Fatal and serious infections, including opportunistic infections, occurred in patients during treatment with MONJUVI and following the last dose. 73% of the 81 patients developed an infection. The most frequent infections were respiratory tract infection, urinary tract infection, bronchitis, nasopharyngitis and pneumonia. Grade 3 or higher infection occurred in 30% of the 81 patients. The most frequent grade 3 or higher infection was pneumonia. Infection-related deaths were reported in 2.5% of the 81 patients. Monitor your patients for signs and symptoms of infection and manage as appropriate.

NARRATOR: Because MONJUVI may cause fetal B-cell depletion when administered to a pregnant woman, you should advise pregnant women of the potential risk to a fetus, and advise women of reproductive potential to use effective contraception during treatment with MONJUVI and for at least 3 months after the last dose. The combination of MONJUVI with lenalidomide is contraindicated in pregnant women. Refer to the lenalidomide prescribing information on use during pregnancy.

DR MEHTA: In this case, the patient's disease progressed within 12 months of their diagnosis and they want to stay in their local area to receive treatment. Their disease has progressed quickly, despite initial treatment with CD20-containing therapy, so the goal is to stop or slow its progression and time is of the essence. This patient doesn’t have a support system to rely on, so their preference is to stay with their current healthcare team.

DR MEHTA: The physician intends to initiate therapy immediately for this patient, with the goal of achieving a sustained response. Let’s take a look at why MONJUVI may be a suitable option for a patient like this one.

DR MEHTA: In our hypothetical example, the patient is 65 years old, has an intermediate-high to high risk IPI of 3, ECOG of 1, and is at Ann Arbor stage 3. They’ve also experienced hypertension and they are eager to initiate treatment.

DR MEHTA: The treatment history for our hypothetical patient looks like this:

  • After 4 cycles of R-CHOP, they achieved a PR, which was maintained through the completion of first-line therapy
  • Their disease progressed after a quick relapse—4 months following first-line therapy
  • and they declined autologous stem cell transplant based on their lack of a support system and their preference to stay with their current care team, but are still seeking further treatment

DR XAVIER: After previously receiving R-CHOP, the patient may not want to pursue salvage chemotherapy. MONJUVI is an option that may be appropriate for this patient.

DR XAVIER: MONJUVI is a targeted immunotherapy for adult patients with DLBCL who have received at least 1 prior therapy, in combination with lenalidomide.

DR MEHTA: Let’s take a look at some key data from L-MIND, an open-label, multicenter, single-arm phase 2 study of treatment with MONJUVI and lenalidomide.

DR XAVIER: L-MIND included patients with relapsed or refractory DLBCL after 1 to 3 prior systemic therapies, including a CD20-containing therapy. They were not eligible for, or refused, autologous stem cell transplant.

DR XAVIER: Primary refractory patients were defined in L-MIND as those whose DLBCL relapsed or progressed after at least 3 months from completion of prior CD20-containing therapy. The study included only patients who met this definition.

DR MEHTA: The primary endpoint was the best overall response rate, which was defined as the proportion of complete and partial responders. Duration of response was a select secondary endpoint. Efficacy was assessed by an Independent Review Committee using the International Working Group Response Criteria.

DR MEHTA: Patients like the one we just described were well represented in the L-MIND study. Out of the 71 patients that were evaluated for efficacy, 20% had primary refractory disease, 45% were refractory to their last prior therapy, and 42% were refractory to rituximab.

DR MEHTA: Also, 24% of patients had relapsed or progressed within the first 12 months after initial diagnosis. Lastly, 52% had IPI scores of 3 to 5, which are in the intermediate-high to high-risk range.

DR XAVIER: In the primary analysis, the best overall response rate was 55% at 1 year.

DR MEHTA: MONJUVI, in combination with lenalidomide, was granted accelerated approval based on the 1-year primary analysis of the L-MIND study. The data for the 3-year analysis of the L-MIND study has not yet been submitted to or reviewed by the FDA. The status with respect to potential inclusion of these data in the final, FDA-approved labeling has yet to be determined. This important caveat applies to all the 3-year analyses that we will discuss during this presentation.

DR XAVIER: The best overall response rate was 54% in the 3-year follow-up analysis.

DR XAVIER: In the L-MIND study, the median time to response (partial or complete) was 2 months. The median time to CR was 10.9 months and the median time to PR was 1.9 months.

DR XAVIER: This analysis is exploratory in nature. These results should be interpreted with caution due to single-arm studies not adequately characterizing time-to-event endpoints, and the small sample size, which may lead to estimates that are unstable. Please note that this important caveat applies to all the exploratory analyses that we will discuss during this presentation.

DR MEHTA: Let’s take a look at some more data from the 3-year analysis. We can examine the response rates in patients who were treated with MONJUVI and lenalidomide in the second line, and in the third line or later.

DR MEHTA: In patients who received 1 prior therapy, the best overall response rate was 63%. Of these patients, 43% achieved a complete response, and 20% achieved a partial response. In patients who received 2 or more prior therapies, the best overall response rate was 44%. 28% of these patients achieved a complete response and 17% achieved a partial response.

DR MEHTA: An exploratory analysis was conducted as a part of the 1-year analysis that measured overall response rates by subgroup.

DR XAVIER: This analysis is exploratory in nature, and L-MIND was not designed or powered to evaluate and compare multiple subgroups. These results should be interpreted with caution given the small sample size, which may lead to estimates that are unstable.

DR MEHTA: 53% of patients whose disease was refractory to the prior line of therapy achieved an overall response, as did 50% of those who were refractory to rituximab, 49% of those with an intermediate-high to high-risk IPI score of 3 to 5, and 56% with Ann Arbor stage 3 to 4 disease.

DR XAVIER: We also saw that patients achieved a 21.7-month median duration of response in the primary analysis and a 43.9-month median duration of response in the 3-year follow-up analysis.

DR MEHTA: This swimmer plot shows the duration of response for each patient who experienced a response during the L-MIND study. Duration of response was captured from the time the initial response began for each patient. This graph represents 38 out of the 71 patients who experienced a response. Two patients started a new anti-cancer treatment immediately after a response was recorded at the end of the treatment assessment. They are still included as responders but did not record any ongoing response with MONJUVI and lenalidomide.

DR MEHTA: For patients whose response has stopped, events may include tumor progression, death, or beginning of a new anti-cancer treatment.

DR MEHTA: The initial assessment of efficacy or disease response was performed and recorded at Cycle 3, Day 1. As you can see, the majority of responding patients, which was 24 out of 38, or 63%, achieved a complete response at some point during this assessment, and nearly 50%, or 11 out of 24 of those complete responses, were observed at the first efficacy assessment (2 months).

DR MEHTA: Orange dots represent the time points when a partial response became a complete response.

DR XAVIER: The fact that 40%, or 16 out of 38 responding patients, either converted from a partial response to a complete response, or maintained an ongoing partial response, shows how important it is for patients to continue treatment with MONJUVI and lenalidomide according to the treatment schedule, as long as there is no disease progression or unacceptable toxicity.

DR XAVIER: As we discussed when reviewing the 3-year follow-up analysis, the median duration of response based on Kaplan-Meier estimates was 43.9 months, demonstrating sustained remission in patients who responded to treatment with MONJUVI + lenalidomide.

DR XAVIER: MONJUVI is a potential option for this patient, whose disease progressed within the first year after diagnosis and who wants to stay in their local area to receive treatment from their current care team.

DR XAVIER: Now let’s review some important safety data.

DR MEHTA: The most common adverse reactions in 10% or more of patients are summarized here. The most common hematological adverse reactions were neutropenia, anemia, and thrombocytopenia. 49% of patients had grade 3 or 4 neutropenia, 17% had grade 3 or 4 thrombocytopenia, and 12% of patients had grade 3 or 4 febrile neutropenia.

DR XAVIER: This table summarizes other clinically relevant adverse reactions that occurred in less than 10% of patients in L-MIND. Some adverse reactions to be aware of include lymphopenia (6%), infusion-related reactions (6%), sepsis (4.9%), weight decreased (4.9%), arthralgia (9%), pain in extremity (9%), headache (9%), paresthesia (7%), dysgeusia (6%), nasal congestion (4.9%), and erythema (4.9%).

DR XAVIER: For details about additional clinically relevant adverse reactions, please refer to the full Prescribing Information.

DR MEHTA: In addition, select laboratory abnormalities that worsened from baseline in more than 20% of patients receiving MONJUVI are listed here. Noteworthy laboratory abnormalities include the following: glucose increased in 49% of patients, and grade 3/4 in 5% of patients; gamma glutamyl transferase increased in 34% of patients, and grade 3/4 in 5% of patients; urate increased in 20% of patients, and grade 3/4 in 7% of patients; phosphate decreased in 20% of patients, and grade 3/4 in 5% of patients; and activated partial thromboplastin time increased in 46% of patients, and grade 3/4 in 4.1% of patients.

DR MEHTA: For details about additional laboratory abnormalities, please refer to the full Prescribing Information.

DR XAVIER: Let’s take a look at hematologic toxicity management and dosing modifications in L-MIND. 44% of patients received concomitant granulocyte-colony stimulating factor. 46% of patients had at least 1 dose reduction of lenalidomide. 78% of patients were able to receive a lenalidomide dose of at least 20 milligrams per day over the duration of their treatment.

DR XAVIER: Permanent discontinuation of MONJUVI or lenalidomide due to an adverse reaction occurred in 25% of patients and permanent discontinuation of MONJUVI due to an adverse reaction occurred in 15%.

DR XAVIER: Dosage interruptions of MONJUVI or lenalidomide due to an adverse reaction occurred in 69% of patients and dosage interruption of MONJUVI due to an adverse reaction occurred in 65%.

DR XAVIER: For this patient, whose disease progressed within 12 months of their initial diagnosis and who wants to stay in their local area to receive treatment from their current care team, MONJUVI provides an important balance between efficacy and tolerability. To learn more about other patients in whom MONJUVI may be an option, please watch the other videos in this series and visit our website at MonjuviHCP.com. Now we will share the Important Safety Information about MONJUVI.

Important Safety Information

NARRATOR: Contraindications

NARRATOR: None.

Warnings and Precautions

Infusion-Related Reactions

NARRATOR: MONJUVI can cause infusion-related reactions (IRRs). In L-MIND, infusion-related reactions occurred in 6% of the 81 patients. Eighty percent of infusion-related reactions occurred during cycle 1 or 2. Signs and symptoms included fever, chills, rash, flushing, dyspnea, and hypertension. These reactions were managed with temporary interruption of the infusion and/or with supportive medication. Premedicate patients prior to starting MONJUVI infusion. Monitor patients frequently during infusion. Based on the severity of the infusion-related reaction, interrupt or discontinue MONJUVI. Institute appropriate medical management.

Myelosuppression

NARRATOR: MONJUVI can cause serious or severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. In L-MIND, Grade 3 neutropenia occurred in 25% of patients, thrombocytopenia in 12%, and anemia in 7%. Grade 4 neutropenia occurred in 25% and thrombocytopenia in 6%. Neutropenia led to treatment discontinuation in 3.7% of patients.

NARRATOR: Monitor complete blood counts (CBC) prior to administration of each treatment cycle and throughout treatment. Monitor patients with neutropenia for signs of infection. Consider granulocyte colony-stimulating factor (G-CSF) administration. Withhold MONJUVI based on the severity of the adverse reaction. Refer to the lenalidomide prescribing information for dosage modifications.

Infections

NARRATOR: Fatal and serious infections, including opportunistic infections, occurred in patients during treatment with MONJUVI and following the last dose.

NARRATOR: In L-MIND, 73% of the 81 patients developed an infection. The most frequent infections were respiratory tract infection (24%), urinary tract infection (17%), bronchitis (16%), nasopharyngitis (10%) and pneumonia (10%). Grade 3 or higher infection occurred in 30% of the 81 patients. The most frequent grade 3 or higher infection was pneumonia (7%). Infection-related deaths were reported in 2.5% of the 81 patients.

NARRATOR: Monitor patients for signs and symptoms of infection and manage infections as appropriate.

Embryo-Fetal Toxicity

NARRATOR: Based on its mechanism of action, MONJUVI may cause fetal B-cell depletion when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise women of reproductive potential to use effective contraception during treatment with MONJUVI and for at least 3 months after the last dose.

NARRATOR: MONJUVI is initially administered in combination with lenalidomide. The combination of MONJUVI with lenalidomide is contraindicated in pregnant women because lenalidomide can cause birth defects and death of the unborn child. Refer to the lenalidomide prescribing information on use during pregnancy.

Adverse Reactions

NARRATOR: Serious adverse reactions occurred in 52% of patients who received MONJUVI. Serious adverse reactions in ≥6% of patients included infections (26%), including pneumonia (7%), and febrile neutropenia (6%). Fatal adverse reactions occurred in 5% of patients who received MONJUVI, including cerebrovascular accident (1.2%), respiratory failure (1.2%), progressive multifocal leukoencephalopathy (1.2%) and sudden death (1.2%).

NARRATOR: Permanent discontinuation of MONJUVI or lenalidomide due to an adverse reaction occurred in 25% of patients and permanent discontinuation of MONJUVI due to an adverse reaction occurred in 15%. The most frequent adverse reactions which resulted in permanent discontinuation of MONJUVI were infections (5%), nervous system disorders (2.5%), respiratory, thoracic, and mediastinal disorders (2.5%).

NARRATOR: Dosage interruptions of MONJUVI or lenalidomide due to an adverse reaction occurred in 69% of patients and dosage interruption of MONJUVI due to an adverse reaction occurred in 65%. The most frequent adverse reactions which required a dosage interruption of MONJUVI were blood and lymphatic system disorders (41%), and infections (27%).

NARRATOR: The most common adverse reactions (≥20%) were neutropenia (51%), fatigue (38%), anemia (36%), diarrhea (36%), thrombocytopenia (31%), cough (26%), pyrexia (24%), peripheral edema (24%), respiratory tract infection (24%), and decreased appetite (22%).

NARRATOR: You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to MORPHOSYS US INC. at (844) 667-1992.

NARRATOR: Please see the full Prescribing Information for additional Important Safety Information available at MONJUVI.com.

DR MEHTA: Following an assessment of clinical factors, consider targeted immunotherapy with MONJUVI as an option for the second-line treatment of DLBCL in transplant-ineligible patients who want to continue treatment with their current care team, receive outpatient treatment, access treatment in a local office or clinic, and/or receive treatment in a timely manner.

DR XAVIER: On behalf of Dr Mehta, I’m Dr Xavier. Thank you for joining us for this presentation. Be sure to visit MonjuviHCP.com to learn more about treatment with MONJUVI and lenalidomide.

Efficacy and Safety

Watch a lymphoma specialist provide an overview of the characteristics of patients included in the L-MIND study, as well as an analysis of key efficacy and safety results of treatment with MONJUVI and lenalidomide.

Transcript

DOCTOR: Hello, I’m Dr. Eradat, Associate Clinical Professor of Medicine at the David Geffen School of Medicine at UCLA. Today, we will discuss the efficacy and safety of MONJUVI in combination with lenalidomide, followed by MONJUVI as monotherapy, as a second or later line of treatment in non-transplant–eligible adult patients who have diffuse large B-cell lymphoma. We’ll review the data from the L-MIND clinical trial, looking at results from both the 1-year primary analysis as well as the 3-year follow-up.

NARRATOR: MONJUVI (tafasitamab-cxix), in combination with lenalidomide, is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma not otherwise specified, including diffuse large B-cell lymphoma arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant.

NARRATOR: This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial or trials.

NARRATOR: MONJUVI can cause infusion-related reactions. In the L-MIND trial, infusion-related reactions, or IRRs, occurred in 6% of the 81 patients. Eighty percent of the IRRs occurred during cycle 1 or 2. Patients should be premedicated and monitored frequently during their infusion and based on the severity of the IRRs, interrupt or discontinue MONJUVI and institute appropriate medical management.

NARRATOR: In addition, MONJUVI can cause serious or severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. Patients’ complete blood counts should be monitored prior to administration of each treatment cycle and throughout treatment. Patients with neutropenia should be monitored for signs of infection and MONJUVI should be withheld based on the severity of the adverse reaction.

NARRATOR: Fatal and serious infections, including opportunistic infections, occurred in patients during treatment with MONJUVI and following the last dose. Monitor your patients for signs and symptoms of infection and manage as appropriate.

NARRATOR: Because MONJUVI may cause fetal B-cell depletion when administered to a pregnant woman, you should advise pregnant women of the potential risk to a fetus, and advise women of reproductive potential to use effective contraception during treatment with MONJUVI and for at least 3 months after the last dose.

NARRATOR: We will be discussing more about the safety profile during this presentation.

DOCTOR: MONJUVI is a humanized CD19-directed monoclonal antibody that, upon binding to CD19, mediates B-cell lysis through apoptosis and immune effector mechanisms, including antibody-directed cellular phagocytosis, or ADCP, and antibody-directed cellular cytotoxicity, or ADCC.

DOCTOR: In studies conducted in vitro in diffuse large B-cell lymphoma tumor cells, tafasitamab-cxix, in combination with lenalidomide, resulted in increased ADCC activity compared to tafasitamab-cxix or lenalidomide alone.

DOCTOR: L-MIND was an open-label, multicenter, single-arm, phase 2 study that evaluated the efficacy and safety of MONJUVI in combination with lenalidomide in adult patients with relapsed or refractory diffuse large B-cell lymphoma.

DOCTOR: L-MIND included patients with relapsed or refractory diffuse large B-cell lymphoma after 1 to 3 prior systemic therapies, including a CD20-containing therapy. Patients were not eligible for, or refused, autologous stem cell transplant.

DOCTOR: The primary endpoint was the overall response rate, which was defined as the proportion of complete and partial responders.

DOCTOR: Duration of response was a select secondary endpoint.

DOCTOR: Efficacy was assessed by an Independent Review Committee using the International Working Group Response Criteria.

DOCTOR: Treatment was administered in 28-day cycles. MONJUVI was administered on days 1, 8, 15, and 22 of cycles 1 through 3, with an additional loading dose on day 4 of cycle 1. After cycle 3, MONJUVI was administered on days 1 and 15. Lenalidomide was administered on days 1 through 21 of cycles 1 through 12 only.

DOCTOR: Please see the Prescribing Information to learn more about administering premedications to minimize infusion-related reactions.

DOCTOR: This table shows the baseline characteristics of the patients with relapsed or refractory diffuse large B-cell lymphoma in the L-MIND study. Let’s take a look at some of the characteristics of patients in the study.

DOCTOR: Nearly 20% of patients had primary refractory disease.

DOCTOR: In addition, 49% received 1 prior line of therapy; 51% received 2 to 4 prior lines.

DOCTOR: For nearly 24% of patients, the first documented relapse or progression occurred within the first 12 months after initial diagnosis. Half of the patients studied were categorized as intermediate-high and high risk based on their IPI score.

DOCTOR: This trial included patients whose diffuse large B-cell lymphoma reoccurred or did not respond after 1 to 3 prior systemic therapies, including a CD20-containing therapy.

DOCTOR: Patients were not candidates for autologous stem cell transplant based on their age, comorbidities, whether they were refractory to salvage chemotherapy, and whether they refused high-dose chemotherapy and stem cell transplant.

DOCTOR: L-MIND included primary refractory patients and those with an IPI score of 3 to 5. In separate analyses, these characteristics of high-risk DLBCL were linked to poor outcomes.

DOCTOR: Let’s review the overall response rate shown with the combination of MONJUVI and lenalidomide in the 1-year primary analysis of L-MIND.

DOCTOR: Among the 71 patients with relapsed or refractory diffuse large B-cell lymphoma confirmed by central laboratory the overall response rate was 55%, which included 37% of patients who had a complete response. 18% of the patients had a partial response.

DOCTOR: This analysis is exploratory in nature, and L-MIND was not designed or powered to evaluate and compare multiple subgroups. These results should be interpreted with caution given the small sample size, which may lead to estimates that are unstable.

DOCTOR: The overall response rate was 63% for patients with 1 line of prior therapy, and 47% for those with 2 or more lines of prior therapy.

DOCTOR: The overall response rate was 62% for patients with low or low-intermediate risk and 49% for patients with intermediate-high and high risk, based on the IPI score.

DOCTOR: Now let’s take a look at the overall response rate data from the 3-year follow-up analysis. This analysis was conducted after the last patient enrolled had completed at least 35 months of follow-up.

DOCTOR: Among the same 71 patients with relapsed or refractory diffuse large B-cell lymphoma, the overall response rate was 54%, including 35% of patients who had a complete response, and 18% of patients who had a partial response.

DOCTOR: Let’s look at the duration of response data from L-MIND in patients who received treatment with the combination of MONJUVI and lenalidomide.

DOCTOR: In the 1-year primary analysis, the median duration of response among the 71 patients with relapsed or refractory diffuse large B-cell lymphoma was 21.7 months.

DOCTOR: Following 3 years of follow-up of the same 71 patients, the median duration of response was 43.9 months.

DOCTOR: The safety profile of the MONJUVI and lenalidomide combination was evaluated in the full L-MIND study population of 81 patients.

DOCTOR: Let’s begin by summarizing the adverse reactions leading to discontinuation, death, and serious adverse reactions.

DOCTOR: 52% of patients experienced serious adverse reactions, 5% experienced fatal adverse reactions, and 25% experienced an adverse reaction that led to discontinuation.

DOCTOR: The most common adverse reactions that occurred in more than 20% of patients are listed here.

DOCTOR: The most common adverse reactions in 10% or more of patients are summarized here. The most common hematological adverse reactions were neutropenia, anemia, and thrombocytopenia. 49% of patients had grade 3 or 4 neutropenia, 17% had grade 3 or 4 thrombocytopenia, and 12% of patients had grade 3 or 4 febrile neutropenia.

DOCTOR: Other clinically relevant adverse reactions that occurred in less than 10% of patients in L-MIND, such as the 6% rate of infusion-related reactions, are summarized in this table.

DOCTOR: In addition, some select laboratory abnormalities that worsened from baseline in more than 20% of patients receiving MONJUVI are listed here.

DOCTOR: Let’s take a look at hematologic toxicity management and dosing modifications in L-MIND. More than 40% of patients received concomitant granulocyte colony-stimulating factor. Nearly half of patients had at least 1 dose reduction of lenalidomide. Nearly 80% of patients were able to receive a lenalidomide dose of at least 20 milligrams per day over the duration of their treatment. Permanent discontinuation of MONJUVI or lenalidomide due to an adverse reaction occurred in 25% of patients and permanent discontinuation of MONJUVI due to an adverse reaction occurred in 15%. Dosage interruptions of MONJUVI or lenalidomide due to an adverse reaction occurred in 69% of patients and dosage interruption of MONJUVI due to an adverse reaction occurred in 65%.

DOCTOR: Thank you for joining me for this presentation. Remember, MONJUVI, in combination with lenalidomide, is an FDA-approved treatment indicated in non-transplant–eligible adult patients with relapsed or refractory diffuse large B-cell lymphoma who have received at least 1 prior therapy.

NARRATOR: Indications & Usage

NARRATOR: MONJUVI (tafasitamab-cxix), in combination with lenalidomide, is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT).

NARRATOR: This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial or trials.

Important Safety Information

NARRATOR: Contraindications

NARRATOR: None.

Warnings and Precautions

Infusion-Related Reactions

NARRATOR: MONJUVI can cause infusion-related reactions (IRRs). In L-MIND, infusion-related reactions occurred in 6% of the 81 patients. Eighty percent of infusion-related reactions occurred during cycle 1 or 2. Signs and symptoms included fever, chills, rash, flushing, dyspnea, and hypertension. These reactions were managed with temporary interruption of the infusion and/or with supportive medication. Premedicate patients prior to starting MONJUVI infusion. Monitor patients frequently during infusion. Based on the severity of the infusion-related reaction, interrupt or discontinue MONJUVI. Institute appropriate medical management.

Myelosuppression

NARRATOR: MONJUVI can cause serious or severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. In L-MIND, Grade 3 neutropenia occurred in 25% of patients, thrombocytopenia in 12%, and anemia in 7%. Grade 4 neutropenia occurred in 25% and thrombocytopenia in 6%. Neutropenia led to treatment discontinuation in 3.7% of patients.

NARRATOR: Monitor complete blood counts (CBC) prior to administration of each treatment cycle and throughout treatment. Monitor patients with neutropenia for signs of infection. Consider granulocyte colony-stimulating factor (G-CSF) administration. Withhold MONJUVI based on the severity of the adverse reaction. Refer to the lenalidomide prescribing information for dosage modifications.

Infections

NARRATOR: Fatal and serious infections, including opportunistic infections, occurred in patients during treatment with MONJUVI and following the last dose.

NARRATOR: In L-MIND, 73% of the 81 patients developed an infection. The most frequent infections were respiratory tract infection (24%), urinary tract infection (17%), bronchitis (16%), nasopharyngitis (10%) and pneumonia (10%). Grade 3 or higher infection occurred in 30% of the 81 patients. The most frequent grade 3 or higher infection was pneumonia (7%). Infection-related deaths were reported in 2.5% of the 81 patients.

NARRATOR: Monitor patients for signs and symptoms of infection and manage infections as appropriate.

Embryo-Fetal Toxicity

NARRATOR: Based on its mechanism of action, MONJUVI may cause fetal B-cell depletion when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise women of reproductive potential to use effective contraception during treatment with MONJUVI and for at least 3 months after the last dose.

NARRATOR: MONJUVI is initially administered in combination with lenalidomide. The combination of MONJUVI with lenalidomide is contraindicated in pregnant women because lenalidomide can cause birth defects and death of the unborn child. Refer to the lenalidomide prescribing information on use during pregnancy.

Adverse Reactions

NARRATOR: Serious adverse reactions occurred in 52% of patients who received MONJUVI. Serious adverse reactions in ≥6% of patients included infections (26%), including pneumonia (7%), and febrile neutropenia (6%). Fatal adverse reactions occurred in 5% of patients who received MONJUVI, including cerebrovascular accident (1.2%), respiratory failure (1.2%), progressive multifocal leukoencephalopathy (1.2%) and sudden death (1.2%).

NARRATOR: Permanent discontinuation of MONJUVI or lenalidomide due to an adverse reaction occurred in 25% of patients and permanent discontinuation of MONJUVI due to an adverse reaction occurred in 15%. The most frequent adverse reactions which resulted in permanent discontinuation of MONJUVI were infections (5%), nervous system disorders (2.5%), respiratory, thoracic and mediastinal disorders (2.5%).

NARRATOR: Dosage interruptions of MONJUVI or lenalidomide due to an adverse reaction occurred in 69% of patients and dosage interruption of MONJUVI due to an adverse reaction occurred in 65%. The most frequent adverse reactions which required a dosage interruption of MONJUVI were blood and lymphatic system disorders (41%), and infections (27%).

NARRATOR: The most common adverse reactions (≥20%) were neutropenia (51%), fatigue (38%), anemia (36%), diarrhea (36%), thrombocytopenia (31%), cough (26%), pyrexia (24%), peripheral edema (24%), respiratory tract infection (24%), and decreased appetite (22%).

NARRATOR: You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to MORPHOSYS US INC. at (844) 667-1992.

NARRATOR: Please see the full Prescribing Information for additional Important Safety Information available at MONJUVI.com.

MOA

Learn more about CD19 targeting and the mechanism of action (MOA) for MONJUVI.

Transcript

MONJUVI (tafasitamab-cxix), in combination with lenalidomide, is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT).

This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Important Safety Information

Contraindications: None

Warnings and Precautions:

  • Infusion-Related Reactions (IRRs). MONJUVI can cause IRRs, including fever, chills, rash, flushing, dyspnea, and hypertension. Premedicate patients and monitor frequently during infusion. Based on the severity of the IRR, interrupt or discontinue MONJUVI and institute appropriate medical management.
  • Myelosuppression. MONJUVI can cause serious or severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. Monitor complete blood counts (CBC) prior to administration of each treatment cycle and throughout treatment. Monitor patients with neutropenia for signs of infection. Consider granulocyte colony-stimulating factor administration. Withhold MONJUVI based on the severity of the adverse reaction. Refer to the lenalidomide prescribing information for dosage modifications.
  • Infections. Fatal and serious infections, including opportunistic infections, occurred in patients during treatment with MONJUVI and following the last dose. 73% of the 81 patients developed an infection. The most frequent infections were respiratory tract infection, urinary tract infection, bronchitis, nasopharyngitis and pneumonia. Grade 3 or higher infection occurred (30% of 81 patients). The most frequent grade 3 or higher infection was pneumonia. Infection-related deaths were reported (2.5% of 81 patients). Monitor patients for signs and symptoms of infection and manage infections as appropriate.
  • Embryo-Fetal Toxicity. Based on its mechanism of action, MONJUVI may cause fetal B-cell depletion when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus and women of reproductive potential to use effective contraception during treatment with MONJUVI and for at least 3 months after the last dose. The combination of MONJUVI with lenalidomide is contraindicated in pregnant women. Refer to the lenalidomide prescribing information on use during pregnancy.

Adverse Reactions: The most common adverse reactions (≥20%) were neutropenia (51%), fatigue (38%), anemia (36%), diarrhea (36%), thrombocytopenia (31%), cough (26%), pyrexia (24%), peripheral edema (24%), respiratory tract infection (24%), and decreased appetite (22%).

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to MORPHOSYS US INC. at (844) 667-1992.

Please see the full Prescribing Information for additional Important Safety Information.

Dosing

Learn about the preparation and administration of MONJUVI.

Transcript

Thank you for joining this presentation about the dosage and administration of MONJUVI. In this video, you will learn how to administer MONJUVI to your patients with relapsed or refractory DLBCL. Erin Blackwell, an Oncology Clinical Nurse Educator from Incyte, will show you how to prepare the infusion. Erin has been a registered nurse for more than 8 years, and has worked in a variety of roles as an oncology and infusion nurse. You will also learn more about the treatment schedule, how to manage adverse reactions if they occur, what to advise your patients about possible adverse reactions, and where to find support and educational resources.

Before your patient’s first day of treatment with MONJUVI, discussing the details of the infusion process may help put him or her at ease. Here are a few important points you may want to mention to your patients:

Patients should consider bringing a caregiver to their appointments. Having a caregiver present can be an important means of support. Caregivers can assist patients with remembering the details of both their symptoms and treatment. They can also help provide clarification in conversations with the treatment team.

Explain that lab work may be done before or during infusion appointments, which may impact the length of appointments. Clarify how long the infusion will take on the first appointment and on subsequent visits. We will discuss this in more detail in the Administration section of this presentation. Encourage patients to bring reading materials or something to keep them occupied during their infusion. Suggest that patients dress in warm and comfortable clothing. Discuss the need for premedications, given prior to the infusion, to help minimize infusion-related reactions. We will talk more about this in the Premedications section of this presentation.

MONJUVI is the first and only FDA-approved second-line therapy for adult non-transplant–eligible patients with diffuse large B-cell lymphoma, or DLBCL, in combination with lenalidomide. Additionally, MONJUVI is the only CD19-targeted monoclonal antibody that can be administered in your office. This allows patients with DLBCL to continue to be treated in the office or clinic after relapse or first-line failure, preserving their continuity of care, and making treatment accessible. MONJUVI (tafasitamab-cxix), in combination with lenalidomide, is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant.

This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial or trials.

MONJUVI can cause infusion-related reactions. In the L-MIND trial, infusion-related reactions, or IRRs, occurred in 6% of the 81 patients. Eighty percent of the IRRs occurred during cycle 1 or 2. Patients should be premedicated and monitored frequently during their infusion and based on the severity of the IRRs, interrupt or discontinue MONJUVI and institute appropriate medical management.

In addition, MONJUVI can cause serious or severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. Patient’s complete blood counts should be monitored prior to administration of each treatment cycle and throughout treatment. Patients with neutropenia should be monitored for signs of infection and MONJUVI should be withheld based on the severity of the adverse reaction.

Fatal and serious infections, including opportunistic infections, occurred in patients during treatment with MONJUVI and following the last dose. Monitor your patients for signs and symptoms of infection and manage as appropriate. Lastly, because MONJUVI may cause fetal B-cell depletion when administered to a pregnant woman, you should advise pregnant women of the potential risk to a fetus, and advise women of reproductive potential to use effective contraception during treatment with MONJUVI and for at least 3 months after the last dose. We will be discussing more about the safety profile during this presentation.

Premedication, seen here, should be administered 30 minutes to 2 hours prior to starting MONJUVI infusion to minimize infusion-related reactions. Premedications may include acetaminophen, histamine H1 receptor antagonists, histamine H2 receptor antagonists, and/or glucocorticosteroids. Administer premedications 30 minutes to 2 hours before starting the MONJUVI infusion to minimize infusion-related reactions. If a patient experiences an infusion-related reaction, administer premedications before each subsequent infusion. For patients who did not experience infusion-related reactions during the first 3 infusions, premedication is optional before each subsequent infusion.

The recommended dose of MONJUVI is 12 milligrams per kilogram based on actual body weight. Administer MONJUVI in combination with lenalidomide 25 milligrams orally on days 1 to 21 of each 28-day cycle for a maximum of 12 cycles. For example, a patient weighing 176 pounds, or 80 kilograms, would require 960 milligrams of MONJUVI. This would require 5 vials of MONJUVI reconstituted for dilution in a 250-milliliter bag of 0.9% Sodium Chloride.

Each vial contains 200 mg of MONJUVI. We will be discussing reconstitution and dilution in more detail later in this video. MONJUVI is administered as an intravenous infusion in your office or infusion center, according to the following dosing schedule. This graph shows the treatment schedule up to cycle 12. Each cycle is 28 days long. During the first cycle, MONJUVI is administered on days 1, 4, 8, 15, and 22. During cycles 2 and 3, MONJUVI is administered on days 1, 8, 15, and 22. From cycle 4 onward, MONJUVI is administered only on days 1 and 15. After 12 cycles, continue MONJUVI as monotherapy until disease progression or unacceptable toxicity. In summary, MONJUVI is given weekly during cycles 1 through 3, with a loading dose on day 4 of cycle 1. Beginning with cycle 4, MONJUVI is given every 2 weeks.

It is important to note that 45.7% of patients, or 37 out of 81, had at least one dose reduction of lenalidomide. Additionally, 77.5% of patients, or 62 out of 81, were able to receive a lenalidomide dose of at least 20 milligrams per day over the duration of their treatment. Refer to the lenalidomide prescribing information for lenalidomide dosage recommendations. MONJUVI should be administered by a healthcare professional with immediate access to emergency equipment and appropriate medical support to manage infusion-related reactions. Visit the Interactive Treatment Calendar on our website at MonjuviHCP.com to create a customized treatment schedule for your patients using the infusion number and cycle number at any point during their treatment.

Before administering the infusion, MONJUVI must first be reconstituted and diluted. Let’s review each process, step by step. Calculate the dose in milligrams and determine the number of vials needed. Based on our earlier example, a patient weighing 176 pounds will require 4.8 vials, so a total of 5 vials will need to be reconstituted for dilution. Each vial contains 200 mg of MONJUVI. The average patient will require 4 to 6 vials. However, patients should always be weighed prior to each cycle to confirm the appropriate dosing. Reconstitute each 200-milligram MONJUVI vial with 5 milliliters of Sterile Water for Injection, USP with the stream directed toward the wall of each vial to obtain a final concentration of 40 milligrams per milliliter of tafasitamab-cxix. Gently swirl the vial or vials until the contents have completely dissolved. Do not shake or swirl vigorously. Complete dissolution may take up to 5 minutes. Visually inspect the reconstituted solution for particulate matter or discoloration. The reconstituted solution should appear as a colorless to slightly yellow solution. Discard the vial or vials if the solution is cloudy, discolored, or contains visible particles. Use the reconstituted MONJUVI solution immediately. If needed, store the reconstituted solution in the vial for a maximum of 12 hours either refrigerated at 36oF to 46oF (2oC to 8oC) or room temperature at 68oF to 77oF (20oC to 25oC) before dilution. Protect from light during storage.

Determine the volume, in milliliters, of the 40 milligrams per milliliter reconstituted MONJUVI solution needed based on the required dose. Our 176-pound patient would require 24 milliliters of reconstituted MONJUVI solution. Therefore, 24 milliliters of 0.9% Sodium Chloride would need to be removed from the bag and replaced with reconstituted MONJUVI to create the final diluted product. The final concentration would be 3.84 milligrams per milliliter. The unused portion of reconstituted MONJUVI should be discarded.

Now that we’ve reviewed how to determine the volume of MONJUVI solution you need, I will show you the rest of the dilution process. Remove a volume equal to the required MONJUVI solution from a 250 milliliter 0.9% Sodium Chloride Injection, USP infusion bag and discard it. Withdraw the necessary amount of MONJUVI and slowly dilute in the infusion bag that contains the 0.9% Sodium Chloride Injection, USP to a final concentration of 2 milligrams per milliliter to 8 milligrams per milliliter. Discard any unused portion of MONJUVI remaining in the vial. Gently mix the intravenous bag by slowly inverting the bag. Do not shake. Visually inspect the infusion bag with the diluted MONJUVI infusion solution for particulate matter and discoloration prior to administration.

If not used immediately, store the diluted MONJUVI infusion solution refrigerated for up to 18 hours at 36oF to 46oF (2oC to 8oC) and/or at room temperature for up to 12 hours at 68oF to 77oF (20oC to 25oC). The room temperature storage includes time for infusion. Protect from light during storage. Do not shake or freeze the reconstituted or diluted infusion solutions.

Administer MONJUVI as an intravenous infusion. For the first infusion, use an infusion rate of 70 milliliters per hour for the first 30 minutes, then increase the rate so that the infusion is administered within 1.5 to 2.5 hours. In the L-MIND study, after the first 30 minutes, the rate of infusion was increased to 125 milliliters per hour over a 2-hour period. Administer all subsequent infusions within 1.5 to 2 hours.

In the L-MIND clinical trial, vital signs were measured immediately prior to each infusion, at 15 minutes, 30 minutes, every 60 minutes, and at the end of each infusion. Infuse the entire contents of the bag containing MONJUVI. Do not co-administer other drugs through the same infusion line. No incompatibilities have been observed between MONJUVI with infusion containers made of polypropylene (PP), polyvinylchloride (PVC), polyethylene (PE), polyethylenterephthalate (PET), or glass and infusion sets made of polyurethane (PUR) or PVC.

In the event that adverse reactions occur during treatment with MONJUVI, dosage modifications are recommended. Specific guidance on how to modify the dose in response to infusion-related reactions or myelosuppression is provided in Table 2 in the Prescribing Information. Depending on the severity of the infusion-related reaction, the infusion may need to be interrupted for symptoms to resolve and either resumed at a lower rate, or, in case of Grade 4 reactions, permanently discontinued. Complete blood counts should also be monitored in all patients prior to receiving each MONJUVI treatment cycle and throughout treatment. Manage myelosuppression using dose modifications and growth factor support. Depending on the platelet and neutrophil counts, patients may need to interrupt treatment. After complete blood count recovery, MONJUVI can be resumed at the same dose, but lenalidomide should be resumed at a reduced dose.

Before your patients begin treatment with MONJUVI, there are several important topics to discuss. Infusion-related reactions. Advise patients to contact their healthcare provider if they experience signs and symptoms of infusion-related reactions. Myelosuppression. Fever of 100.4°F (38°C) or greater, or bruising or bleeding, should be reported immediately. Advise patients of the need for periodic monitoring of blood counts. Infections. Fever of 100.4°F (38°C) or greater or signs or symptoms of infection should be reported immediately. Embryo-fetal toxicity. Advise pregnant women of the potential risk to a fetus. Women of reproductive potential should inform their healthcare provider of a known or suspected pregnancy. Advise women of reproductive potential to use effective contraception during treatment with MONJUVI and for at least 3 months after the last dose. Advise patients that lenalidomide has the potential to cause fetal harm and has specific requirements regarding contraception, pregnancy testing, blood and sperm donation, and transmission in sperm. Lenalidomide is only available through a REMS program. Lactation. Advise women not to breastfeed during treatment with MONJUVI and for at least 3 months after the last dose.

MONJUVI is an accessible therapy that can be administered to patients with relapsed or refractory DLBCL in both offices and clinics. My MISSION Support offers personalized patient support and education. When a patient enrolls in My MISSION Support, they may opt into receiving additional support and education from an oncology professional. These professionals are specially trained to support a patient’s ongoing journey with MONJUVI treatment by providing general disease and treatment information, routine phone-based check-ins, and referrals to additional resources. A patient’s doctor should always be their first point of contact for any questions about their condition or treatment.

Indications & Usage

MONJUVI (tafasitamab-cxix), in combination with lenalidomide, is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT).

This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Important Safety Information

Contraindications

None.

Warnings and Precautions

Infusion-Related Reactions

MONJUVI can cause infusion-related reactions (IRRs). In L-MIND, infusion-related reactions occurred in 6% of the 81 patients. Eighty percent of infusion-related reactions occurred during cycle 1 or 2. Signs and symptoms included fever, chills, rash, flushing, dyspnea, and hypertension. These reactions were managed with temporary interruption of the infusion and/or with supportive medication. Premedicate patients prior to starting MONJUVI infusion. Monitor patients frequently during infusion. Based on the severity of the infusion-related reaction, interrupt or discontinue MONJUVI. Institute appropriate medical management.

Myelosuppression

MONJUVI can cause serious or severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. In L-MIND, Grade 3 neutropenia occurred in 25% of patients, thrombocytopenia in 12%, and anemia in 7%. Grade 4 neutropenia occurred in 25% and thrombocytopenia in 6%. Neutropenia led to treatment discontinuation in 3.7% of patients.

Monitor complete blood counts (CBC) prior to administration of each treatment cycle and throughout treatment. Monitor patients with neutropenia for signs of infection. Consider granulocyte colony-stimulating factor (G-CSF) administration. Withhold MONJUVI based on the severity of the adverse reaction. Refer to the lenalidomide prescribing information for dosage modifications.

Infections

Fatal and serious infections, including opportunistic infections, occurred in patients during treatment with MONJUVI and following the last dose.

In L-MIND, 73% of the 81 patients developed an infection. The most frequent infections were respiratory tract infection (24%), urinary tract infection (17%), bronchitis (16%), nasopharyngitis (10%) and pneumonia (10%). Grade 3 or higher infection occurred in 30% of the 81 patients. The most frequent grade 3 or higher infection was pneumonia (7%). Infection-related deaths were reported in 2.5% of the 81 patients.

Monitor patients for signs and symptoms of infection and manage infections as appropriate.

Embryo-Fetal Toxicity

Based on its mechanism of action, MONJUVI may cause fetal B-cell depletion when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise women of reproductive potential to use effective contraception during treatment with MONJUVI and for at least 3 months after the last dose.

MONJUVI is initially administered in combination with lenalidomide. The combination of MONJUVI with lenalidomide is contraindicated in pregnant women because lenalidomide can cause birth defects and death of the unborn child. Refer to the lenalidomide prescribing information on use during pregnancy.

Adverse Reactions

Serious adverse reactions occurred in 52% of patients who received MONJUVI. Serious adverse reactions in ≥6% of patients included infections (26%), including pneumonia (7%), and febrile neutropenia (6%). Fatal adverse reactions occurred in 5% of patients who received MONJUVI, including cerebrovascular accident (1.2%), respiratory failure (1.2%), progressive multifocal leukoencephalopathy (1.2%) and sudden death (1.2%).

Permanent discontinuation of MONJUVI or lenalidomide due to an adverse reaction occurred in 25% of patients and permanent discontinuation of MONJUVI due to an adverse reaction occurred in 15%. The most frequent adverse reactions which resulted in permanent discontinuation of MONJUVI were infections (5%), nervous system disorders (2.5%), respiratory, thoracic and mediastinal disorders (2.5%).

Dosage interruptions of MONJUVI or lenalidomide due to an adverse reaction occurred in 69% of patients and dosage interruption of MONJUVI due to an adverse reaction occurred in 65%. The most frequent adverse reactions which required a dosage interruption of MONJUVI were blood and lymphatic system disorders (41%), and infections (27%).

The most common adverse reactions (≥20%) were neutropenia (51%), fatigue (38%), anemia (36%), diarrhea (36%), thrombocytopenia (31%), cough (26%), pyrexia (24%), peripheral edema (24%), respiratory tract infection (24%), and decreased appetite (22%).

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to MORPHOSYS US INC. at (844) 667-1992.

Please see the full Prescribing Information for additional Important Safety Information.

Patient/Caregiver Testimonials

Meet Maggie, a wife, mother, and grandmother. When Maggie’s DLBCL didn’t fully respond to initial treatment, her healthcare team explained that she was an appropriate patient for MONJUVI. Learn more about her story.

Transcript

MAGGIE: Hi. My name is Maggie. I am married to my husband for 55 years and I have two sons. I have a grandson and I have two great-grandchildren. I worked as a secretary my entire life.

MAGGIE: I love singing in the choir. I also do solo work with the church. I sing with a local community choir, and I do solo work with them. I play bells at church. I love doing that. I love reading. I do studying and I read. I especially love mysteries and thrillers.

MAGGIE: I read outside on my front porch when it’s nice. I love sitting outside where it’s nice and quiet and the atmosphere is just beautiful and hopefully the weather is as well.

MAGGIE: One evening on my way home from choir practice, this individual pulled out in front of me, and I wrecked into her. And going to the hospital, they did a CT scan and through the CT scan they noticed that the enlarged lymph nodes was extreme. They were extensive throughout my whole body. So, they had to do another biopsy and at this time they determined I had cancer.

NARRATOR: Diffuse large B-cell lymphoma, or DLBCL, is the most common type of non-Hodgkin lymphoma, or NHL.

NARRATOR: DLBCL is a fast-growing NHL. It affects B-lymphocytes, also known as B cells, a type of white blood cell that helps the body fight infections. As they develop, cancerous B cells become larger than normal and multiply uncontrollably.

MAGGIE: It was difficult having DLBCL during COVID. I felt isolated. I could only contact my friends and family through texting, through telephone, through video chat. It was a difficult time for me.

BUCK: I supported her by being with her, taking care of her, and just be here 24/7.

BUCK: We’ve had some stressful things happen in our life and we were both there for each other and I just dropped everything and left the world just keep on going by and she was my number one. And she’s still, always is my number one.

MAGGIE: Initially when I was diagnosed with the cancer, they prescribed six cycles of chemotherapy. During my chemotherapy, I had some problems that the medicine affected my heart so I could not continue with that. They had to back off on the amount they gave me and because of that it did not eradicate the cancer.

BUCK: If she has cancer, I have cancer, right, because it’s a team. It’s a team effort and you have to work as a team. You’re going to have to pull together, you have to stand together, be faithful to one another.

MAGGIE: When the cancer came back, it was scary for both of us. We had a lot of trips to be treated for the DLBCL and it took a lot of our time. It completely changed our lives. We could not live our normal lives, because we had to live around this diagnosis.

MAGGIE: When the cancer returned, my original oncologist referred me to another oncologist who specialized in DLBCL. He said that there were four options available. Two of the options would not work for me. But he said one that might work is MONJUVI.

NARRATOR: MONJUVI (tafasitamab-cxix) is a prescription medicine given with lenalidomide to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL) that has come back (relapsed) or that did not respond to previous treatment (refractory) and who cannot receive a stem cell transplant.

NARRATOR: It is not known if MONJUVI is safe and effective in children.

NARRATOR: The approval of MONJUVI is based on a type of response rate. There is an ongoing study to confirm the clinical benefit of MONJUVI.

MAGGIE: I did come home and go online and look up MONJUVI. There was a lot of information available on the website.

MAGGIE: One of the things I did before I went for my infusion was to write any questions down. I did this on my phone so that I had it available and when I got there, I was able to ask them, so I had everything clear in my mind as to what was going to happen.

MAGGIE: With the treatment of MONJUVI, I would go to the local hospital to have an IV infusion and I would take medicine by mouth at home.

MAGGIE: The nurse would hook me up for my infusion and it would take a while for it to run. And while that was running, I would either watch television that they had there, or I would read because I love to read.

MAGGIE: The nurses did explain that there could be side effects with the MONJUVI. I was just to be aware of them and they did explain what they were.

Important Safety Information

NARRATOR: Important information I should know, including possible side effects, about MONJUVI:

NARRATOR: MONJUVI may cause serious side effects, including infusion-related reactions, low blood cell counts, and infections.

NARRATOR: The most common side effects of MONJUVI include feeling tired or weak, diarrhea, cough, fever, swelling of lower legs or hands, respiratory tract infection, and decreased appetite.

NARRATOR: Continue watching to learn more about these and other side effects.

MAGGIE: I have a lot of gratitude for my husband, for my family, for my two sons. They’ve been there to support me the whole way. My family, my friends. They would always touch base with me to see how I was doing, to make sure everything was fine. So, I have a lot of gratitude for everyone that’s been around me.

MAGGIE: We’re on a mission to do more traveling and spend more time together. We especially love to travel to different parts of the country and even out of the country.

MAGGIE: My husband and I are both looking forward to a cruise we have planned to celebrate our 55th wedding anniversary.

MAGGIE: I enjoy going out and working in my garden. I enjoy keeping track of my family, especially my grandson and our two new great-grandchildren. I love speaking with them and seeing pictures of them.

MAGGIE: It is hard hearing that your DLBCL has returned. But I would recommend that you keep an open mind. Stay positive. Keep in touch with your family and friends, because they’re going to uplift you and keep you positive.

MAGGIE: My life now since the DLBCL has changed. I’m not as active as I used to be physically. It seemed to affect my body where I’m not walking as much as I used to. But we still, both my husband and I, keep active. He’s active outside, as well as I am and I’m active in activities in the home and keeping things going here.

MAGGIE: My outlook is very positive. I love life. I live it happily and I’m just glad to be here.

Important Safety Information

NARRATOR: What are the possible side effects of MONJUVI?

NARRATOR: MONJUVI may cause serious side effects, including infusion reactions. Your healthcare provider will monitor you for infusion reactions during your infusion of MONJUVI. Tell your healthcare provider right away if you get fever, chills, flushing, headache, or shortness of breath during an infusion of MONJUVI.

NARRATOR: Low blood cell counts (platelets, red blood cells, and white blood cells). Low blood cell counts are common with MONJUVI, but can also be serious or severe. Your healthcare provider will monitor your blood counts during treatment with MONJUVI. Tell your healthcare provider right away if you get a fever of 100.4 °F (38 °C) or above, or any bruising or bleeding.

NARRATOR: Infections. Serious infections, including infections that can cause death, have happened in people during treatment with MONJUVI and after the last dose. Tell your healthcare provider right away if you get a fever of 100.4 °F (38 °C) or above, or develop any signs or symptoms of an infection.

NARRATOR: The most common side effects of MONJUVI include feeling tired or weak, diarrhea, cough, fever, swelling of lower legs or hands, respiratory tract infection, and decreased appetite.

NARRATOR: These are not all the possible side effects of MONJUVI. Your healthcare provider will give you medicines before each infusion to decrease your chance of infusion reactions. If you do not have any reactions, your healthcare provider may decide that you do not need these medicines with later infusions. Your healthcare provider may need to delay or completely stop treatment with MONJUVI if you have severe side effects.

NARRATOR: Before you receive MONJUVI, tell your healthcare provider about all your medical conditions, including if you have an active infection or have had one recently.

NARRATOR: Are pregnant or plan to become pregnant. MONJUVI may harm your unborn baby. You should not become pregnant during treatment with MONJUVI. Do not receive treatment with MONJUVI in combination with lenalidomide if you are pregnant because lenalidomide can cause birth defects and death of your unborn baby.

NARRATOR: You should use an effective method of birth control (contraception) during treatment and for at least 3 months after your last dose of MONJUVI.

NARRATOR: Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with MONJUVI.

NARRATOR: Are breastfeeding or plan to breastfeed. It is not known if MONJUVI passes into your breastmilk. Do not breastfeed during treatment and for at least 3 months after your last dose of MONJUVI.

NARRATOR: You should also read the lenalidomide Medication Guide for important information about pregnancy, contraception, and blood and sperm donation.

NARRATOR: Tell your healthcare provider about all the medications you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

NARRATOR: Call your doctor for medical advice about side effects. You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to MORPHOSYS US INC. at (844) 667-1992.

NARRATOR: Please see the full Prescribing Information, including Patient Information, for additional Important Safety Information.