Get your patient on Monjuvi (Tafasitamab-Cxix)

Reconstitution

1. Calculate the dose (mg) and determine the number of vials needed.
2. Reconstitute each 200 mg MONJUVI vial with 5 mL Sterile Water for Injection, USP with the stream directed toward the wall of each vial to obtain a final concentration of 40 mg/mL tafasitamab-cxix.
3. Gently swirl the vial(s) until completely dissolved. Do not shake or swirl vigorously. Complete dissolution may take up to 5 minutes.
4. 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(s) if the solution is cloudy, discolored, or contains visible particles.
5. 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°F to 46°F (2°C to 8°C) or room temperature at 68°F to 77°F (20°C to 25°C) before dilution. Protect from light during storage.

Dilution

1. Determine the volume (mL) of the 40 mg/mL reconstituted MONJUVI solution needed based on the required dose.
2. Remove a volume equal to the required MONJUVI solution from a 250 mL 0.9% Sodium Chloride Injection, USP infusion bag and discard it.
3. 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 mg/mL to 8 mg/mL. Discard any unused portion of MONJUVI remaining in the vial.
4. 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.
5. If not used immediately, store the diluted MONJUVI infusion solution refrigerated for up to 18 hours at 36°F to 46°F (2°C to 8°C) and/or at room temperature for up to 12 hours at 68°F to 77°F (20°C to 25°C). The room temperature storage includes time for infusion. Protect from light during storage.

Do not shake or freeze the reconstituted or diluted infusion solutions.

Administration

• Administer MONJUVI as an intravenous infusion.
  • 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 hours.
  • Administer all subsequent infusions within 1.5 to 2 hours.
• 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.

Risk Summary

Based on its mechanism of action, MONJUVI may cause fetal B-cell depletion when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on MONJUVI use in pregnant women to evaluate for a drug-associated risk. Animal reproductive toxicity studies have not been conducted with tafasitamab-cxix.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

MONJUVI is administered in combination with lenalidomide for up to 12 cycles. Lenalidomide can cause embryo-fetal harm and is contraindicated for use in pregnancy. Refer to the lenalidomide prescribing information for additional information. Lenalidomide is only available through a REMS program.

Clinical Considerations

Data

Risk Summary

There are no data on the presence of tafasitamab-cxix in human milk or the effects on the breastfed child or milk production. Maternal immunoglobulin G is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed infant to MONJUVI are unknown. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with MONJUVI and for at least 3 months after the last dose. Refer to lenalidomide prescribing information for additional information.

Pregnancy Testing

Refer to the prescribing information for lenalidomide for pregnancy testing requirements prior to initiating the combination of MONJUVI with lenalidomide.

Contraception

Relapsed or Refractory Diffuse Large B-Cell Lymphoma

The safety of MONJUVI was evaluated in L-MIND [see Clinical Studies (14) ]. Patients (n=81) received MONJUVI 12 mg/kg intravenously in combination with lenalidomide for a maximum of 12 cycles, followed by MONJUVI as monotherapy until disease progression or unacceptable toxicity as follows:

• Cycle 1: Days 1, 4, 8, 15 and 22 of the 28-day cycle;
• Cycles 2 and 3: Days 1, 8, 15 and 22 of each 28-day cycle;
• Cycles 4 and beyond: Days 1 and 15 of each 28-day cycle.

Among patients who received MONJUVI, 57% were exposed for 6 months or longer, 42% were exposed for greater than one year, and 24% were exposed for greater than two years.

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, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, respiratory tract infection, and decreased appetite.

Table 3 summarizes the adverse reactions in L-MIND.

Clinically relevant adverse reactions in <10% of patients who received MONJUVI were:

• Blood and lymphatic system disorders : lymphopenia (6%)
• General disorders and administration site conditions : infusion-related reaction (6%)
• Infections : sepsis (4.9%)
• Investigations : weight decreased (4.9%)
• Musculoskeletal and connective tissue disorders : arthralgia (9%), pain in extremity (9%), musculoskeletal pain (2.5%)
• Neoplasms benign, malignant and unspecified : basal cell carcinoma (1.2%)
• Nervous system disorders: headache (9%), paresthesia (7%), dysgeusia (6%)
• Respiratory, thoracic and mediastinal disorders: nasal congestion (4.9%), exacerbation of chronic obstructive pulmonary disease (1.2%)
• Skin and subcutaneous tissue disorders: erythema (4.9%), alopecia (2.5%), hyperhidrosis (2.5%)

Table 4 summarizes the laboratory abnormalities in L-MIND.

Distribution

The total volume of distribution for tafasitamab-cxix was 9.3 L (95% CI: 8.6, 10 L).

Elimination

The clearance of tafasitamab-cxix was 0.41 L/day (CV: 32%) and terminal elimination half-life was 17 days (95% CI: 15, 18 days).

Specific Populations

Bodyweight (40 to 163 kg) has a significant effect on the pharmacokinetics of tafasitamab-cxix, with higher clearance and volume of distribution expected with higher body weight. No clinically meaningful differences in the pharmacokinetics of tafasitamab-cxix were observed based on age (16 to 90 years), sex, mild to moderate renal impairment (CLcr 30-89 mL/min estimated by the Cockcroft-Gault equation), and mild hepatic impairment (total bilirubin ≤ ULN and AST > ULN, or total bilirubin 1 to 1.5 times ULN and any AST). The effect of severe renal impairment to end-stage renal disease (CLcr < 30 mL/min), moderate to severe hepatic impairment (total bilirubin > 1.5 times ULN and any AST), and race/ethnicity on tafasitamab-cxix pharmacokinetics is unknown.

Drug Interaction Studies

No clinically meaningful differences in tafasitamab-cxix pharmacokinetics were observed when used concomitantly with lenalidomide.