Preparation &
Administration

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 from Incyte will show you how to prepare the infusion. Erin has been a registered nurse for more than eight 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 an 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 a 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 (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.

Important safety information. Contraindications; None. Warnings and precautions; Infusion related reactions (IRRs); MONJUVI (tafasitamab-cxix) 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, lymphopenia, thrombocytopenia, and anemia.

Monitor complete blood count (CBCs) before 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.

In L-MIND, 73% of the 81 patients with DLBCL who received MONJUVI developed an infection. Grade three or higher infection occurred in 30%. The most frequent infections of any grade were respiratory tract infections 51%, including pneumonias and urinary tract infection (17%). Monitor patients for signs and symptoms of infection and manage infections as appropriate. Consider infection prophylaxis per institutional guidelines.

Consider treatment with subcutaneous or intravenous immunoglobulin (IVIg) 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 three 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.

Recommended premedications and prophylactic medication;

Premedications 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 three 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 five vials of MONJUVI reconstituted for dilution in a 250-milliliter bag of 0.9% sodium chloride.

Each vial contains 200 milligrams 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 two and three, MONJUVI is administered on days 1, 8, 15, and 22. From cycle four 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 one through three, with a loading dose on day four of cycle one. Beginning with cycle four,

MONJUVI is given every two 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, including for patients with renal insufficiency.

MONJUVI should be administered by a health care 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 five vials will need to be reconstituted for dilution. Each vial contains 200 milligrams 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 five 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 five 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 36 to 46 degrees Fahrenheit, 2 to 8 degrees Celsius, or room temperature at 68 to 77 degrees Fahrenheit, 20 to 25 degrees Celsius 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 milliliters.

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 36 to 46 degrees Fahrenheit, 2 to 8 degrees Celsius, and/or at room temperature for up to 12 hours at 68 to 77 degrees Fahrenheit, 20 to 25 degrees Celsius.

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 one and a half to two and a half hours. In the L-MIND study, after the first 30 minutes, the rate of infusion was increased to 125 milliliters per hour over a two-hour period.

Administer all subsequent infusions within one and a half to two 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), polyethylene terephthalate (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 two 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 four 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 health care provider if they experience signs and symptoms of infusion-related reactions. Myelosuppression.

Fever of 100.4 degrees Fahrenheit, 38 degrees Celsius, or greater, or signs or symptoms of bruising or bleeding should be reported immediately.

Advise patients of the need for periodic monitoring of blood counts.

Infections.

Fever of 100.4 degrees Fahrenheit, 38 degrees Celsius, 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 health care provider of a known or suspected pregnancy.

Advise women of reproductive potential to use effective contraception during treatment with MONJUVI and for three 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 three 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. IncyteCares for MONJUVI offers personalized patient support and education. When a patient enrolls in IncyteCares for MONJUVI,they may opt in to 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 connections to additional resources. A patient's doctor should always be their first point of contact for any questions about their condition or treatment.

Indications and 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 or trials.

Important safety information. Contraindications; None. Warnings and precautions. Infusion-related reactions; MONJUVI (tafasitamab-cxix) can cause infusion-related reactions (IRRs). In L-MIND,

Infusion-related reactions occurred in 6% of the 81 patients with DLBCL who received MONJUVI. 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 generally 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, lymphopenia, thrombocytopenia, and anemia. In L-MIND, among 81 patients with DLBCL who received MONJUVI, grade three neutropenia was reported in 25%, grade three thrombocytopenia in 12%, and grade three anemia in 7%.

Grade four neutropenia was reported in 25% and grade four thrombocytopenia in 6%. Neutropenia led to treatment discontinuation in 3.7% of the patients. Febrile neutropenia occurred in 12%. Monitor complete blood counts (CBCs) before 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 with DLBCL who received MONJUVI developed an infection. Grade three or higher infection occurred in 30%. Infection-related deaths occurred in 2.5% of patients, including a case of progressive multifocal leukoencephalopathy (PML).

The most frequent grade three or higher infection was pneumonia 7%. The most frequent infections of any grade were respiratory tract infections 51%, including pneumonia and urinary tract infection 17%. Monitor patients for signs and symptoms of infection and manage infections as appropriate. Consider infection prophylaxis as per institutional guidelines. Consider treatment with subcutaneous or intravenous immunoglobulin (IVIg) 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 three months after the last dose. 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 greater than or equal to 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%, and 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 greater than or equal to 20% were neutropenia 51%, respiratory tract infection 51%, fatigue 38%, anemia 36%, diarrhea 36%, thrombocytopenia 31%, cough 26%, pyrexia 24%, peripheral edema 24%, and decreased appetite 22%. 
Please see the Full Prescribing Information available from an Incyte representative or at MONJUVIhcp.com.