Dosage and administration
of MONJUVI + lenalidomide

  1. MONJUVI (tafasitamab-cxix) should be administered by a healthcare professional with immediate access to emergency equipment and appropriate medical support to manage IRRs1
  2. The recommended dose of MONJUVI is 12 mg/kg body weight administered as an intravenous infusion according to the dosing schedule in the table below1
  3. Administer MONJUVI in combination with lenalidomide 25 mg orally on days 1 to 21 of each 28-day cycle for a maximum of 12 cycles, then continue MONJUVI as monotherapy until disease progression or unacceptable toxicity1
  4. Refer to the lenalidomide prescribing information for lenalidomide dosage and recommendations1
  5. Administer MONJUVI as an intravenous infusion1
    1. For the first infusion, use an infusion rate of 70 mL/h for the first 30 minutes, then, increase the rate so that the infusion is administered within 1.5 to 2.5 hours1
      1. In the L-MIND study, after the first 30 minutes, the rate of infusion was increased to 125 mL/h over a 2-hour period2
    2. Administer all subsequent infusions within 1.5 to 2 hours1
    3. In the L-MIND study, vital signs were measured immediately prior to infusion, at 15 minutes (+/- 5 minutes), 30 minutes (+/- 10 minutes), every 60 minutes (+/- 15 minutes), and at the end of the infusion (+/- 20 minutes)2
The cycle length for MONJUVI is 28 days1
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Cycle 1                                                        
DAYS 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
MONJUVI 12 mg/kg
Lenalidomide 25 mg daily
                                                         
Cycles 2 and 3                                                        
DAYS 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
MONJUVI 12 mg/kg
Lenalidomide 25 mg daily
                                                         
                                                         
Cycles 4 to 12                                                        
DAYS 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
MONJUVI 12 mg/kg
Lenalidomide 25 mg daily
                                                         
After 12 cycles, continue MONJUVI                                                        
monotherapy until disease progression                                                        
or unacceptable toxicity                                                        
DAYS 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
MONJUVI 12 mg/kg
                                                         
After 12 cycles, continue MONJUVI monotherapy until disease progression or unacceptable toxicity
DAYS 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
MONJUVI 12 mg/kg
                                                         
  • 45.7% of patients (37/81) had at least one dose reduction of lenalidomide3
  • 77.5% of patients (62/81) were able to receive a lenalidomide dose of ≥20 mg/day over the duration of their treatment3

MONJUVI Preparation and Administration

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.