Tafasitamab-cxix
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alara Ece Dagsali, M.D.
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Overview
Tafasitamab-cxix is a CD19-directed cytolytic monoclonal antibody that is FDA approved for the {{{indicationType}}} of MONJUVI, 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).. Common adverse reactions include The following clinically significant adverse reactions are described elsewhere in the labeling:
- Infusion-related reactions
- Myelosuppression
- Infections.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
MONJUVI, 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).
DOSAGE The recommended dose of MONJUVI is 12 mg/kg based on actual body weight administered as an intravenous infusion according to the dosing schedule.
Administer MONJUVI in combination with lenalidomide 25 mg for a maximum of 12 cycles, then continue MONJUVI as monotherapy until disease progression or unacceptable toxicity. 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 (IRRs).
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Tafasitamab-cxix in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Tafasitamab-cxix in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Tafasitamab-cxix FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Tafasitamab-cxix in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Tafasitamab-cxix in pediatric patients.
Contraindications
None
Warnings
Infusion-Related Reactions MONJUVI can cause infusion-related reactions [see Adverse Reactions (6. 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 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.
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 females of reproductive potential to use effective contraception during treatment with MONJUVI and for at least 3 months after the last dose [see Use in Specific Populations.
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
Clinical Trials Experience
The following clinically significant adverse reactions are described elsewhere in the labeling:
- Infusion-related reactions
- Myelosuppression
- Infections
Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in other clinical trials of another drug and may not reflect the rates observed in practice.
Relapsed or Refractory Diffuse Large B-Cell Lymphoma
The safety of MONJUVI was evaluated in L-MIND. 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.
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%)
Postmarketing Experience
There is limited information regarding Tafasitamab-cxix Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Tafasitamab-cxix Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Tafasitamab-cxix in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Tafasitamab-cxix in women who are pregnant.
Labor and Delivery
Based on its mechanism of action, MONJUVI may cause fetal B-cell depletion when administered to a pregnant woman. 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.
Nursing Mothers
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.
Pediatric Use
The safety and effectiveness of MONJUVI in pediatric patients have not been established.
Geriatic Use
Among 81 patients who received MONJUVI and lenalidomide in L-MIND, 72% were 65 years and older, while 38% were 75 years and older. Clinical studies of MONJUVI did not include sufficient numbers of patients aged 65 and older to determine whether effectiveness differs compared to that of younger subjects. Patients 65 years and older had more serious adverse reactions (57%) than younger patients (39%).
Gender
MONJUVI can cause fetal B-cell depletion when administered to a pregnant woman.
Pregnancy Testing
Refer to the prescribing information for lenalidomide for pregnancy testing requirements prior to initiating the combination of MONJUVI with lenalidomide.
Contraception
Females
Advise females of reproductive potential to use effective contraception during treatment with MONJUVI and for at least 3 months after the last dose. Additionally, refer to the lenalidomide prescribing information for additional recommendations for contraception.
Males
Refer to the lenalidomide prescribing information for recommendations.
Race
There is no FDA guidance on the use of Tafasitamab-cxix with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Tafasitamab-cxix in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Tafasitamab-cxix in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Tafasitamab-cxix in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Tafasitamab-cxix in patients who are immunocompromised.
Administration and Monitoring
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.
Monitoring
There is limited information regarding Tafasitamab-cxix Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Tafasitamab-cxix and IV administrations.
Overdosage
There is limited information regarding Tafasitamab-cxix overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Tafasitamab-cxix Pharmacology in the drug label.
Mechanism of Action
Tafasitamab-cxix is an Fc-modified monoclonal antibody that binds to CD19 antigen expressed on the surface of pre-B and mature B lymphocytes and on several B-cell malignancies, including diffuse large B-cell lymphoma (DLBCL).
Upon binding to CD19, tafasitamab-cxix mediates B-cell lysis through apoptosis and immune effector mechanisms, including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).
In studies conducted in vitro in DLBCL tumor cells, tafasitamab-cxix in combination with lenalidomide resulted in increased ADCC activity compared to tafasitamab-cxix or lenalidomide alone.
Structure
There is limited information regarding Tafasitamab-cxix Structure in the drug label.
Pharmacodynamics
Tafasitamab-cxix reduced peripheral blood B cell counts by 97% after eight days of treatment in patients with relapsed or refractory DLBCL. Nadir, with a reduction of 100%, was reached within 16 weeks of treatment.
Pharmacokinetics
Mean trough concentrations (± standard deviation) were 179 (± 53) μg/mL following administration of MONJUVI at 12 mg/kg on Days 1, 8, 15, and 22 in Cycle 1-3 (plus an additional dose on Cycle 1 Day 4), and 153 (± 68) μg/mL following administration of MONJUVI at 12 mg/kg on Days 1 and 15 from Cycle 4 onwards. Overall maximum tafasitamab-cxix serum concentrations were 483 (±109) μg/mL.
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.
Nonclinical Toxicology
Carcinogenicity and genotoxicity studies have not been conducted with tafasitamab-cxix.
Fertility studies have not been conducted with tafasitamab-cxix.
In the 13-week repeat-dose general toxicity study in cynomolgus monkeys, no adverse effects on male and female reproductive organs were observed up to the highest dose tested, 100 mg/kg/week (approximately 9 times the human exposure based on AUC at the clinical dose of 12 mg/kg/week).
Clinical Studies
The efficacy of MONJUVI in combination with lenalidomide followed by MONJUVI as monotherapy was evaluated in L-MIND, an open-label, multicenter, single arm trial (NCT02399085). Eligible patients had relapsed or refractory DLBCL after 1 to 3 prior systemic therapies, including a CD20-directed cytolytic antibody, and were not candidates for high dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT). Patients received MONJUVI 12 mg/kg intravenously in combination with lenalidomide (25 mg orally on Days 1 to 21 of each 28-day cycle) 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.
Of the 71 patients with DLBCL confirmed by central laboratory who received the combination therapy, the median age was 71 years (range: 41 to 86 years); 55% were males, and 100% had received a prior CD20-containing therapy. Race was collected in 92% of patients; of these, 95% were White, and 3% were Asian. The median number of prior therapies was two; 49% had one prior line of treatment, and 51% had 2 to 4 prior lines. Thirty-two patients (45%) were refractory to their last prior therapy and 30 (42%) were refractory to rituximab. Nine patients (13%) had received prior ASCT. The primary reasons patients were not candidates for ASCT included age (47%), refractoriness to salvage chemotherapy (27%), comorbidities (13%) and refusal of high dose chemotherapy/ASCT (13%).
Efficacy was established based on best overall response rate, defined as the proportion of complete and partial responders, and duration of response, as assessed by an Independent Review Committee using the International Working Group Response Criteria (Cheson, 2007).
How Supplied
MONJUVI (tafasitamab-cxix) for injection is a sterile, preservative-free, white to slightly yellowish lyophilized powder for reconstitution supplied as a 200 mg single-dose vial.
Each 200 mg vial is individually packaged in a carton (NDC 73535–208–01).
Storage
Store refrigerated at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light. Do not shake. Do not freeze.
Images
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Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling
Infusion-Related Reactions
Advise patients to contact their healthcare provider if they experience signs and symptoms of infusion-related reactions.
Myelosuppression
Inform patients about the risk of myelosuppression. Advise patients to immediately contact their healthcare provider for a fever of 100.4°F (38°C) or greater or signs or symptoms of bruising or bleeding. Advise patients of the need for periodic monitoring of blood counts .
Infections
Inform patients about the risk of infections. Advise patients to immediately contact their healthcare provider for a fever of 100.4°F (38°C) or greater or signs or symptoms of infection.
Embryo-Fetal Toxicity
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy. Advise females 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.
Precautions with Alcohol
Alcohol-Tafasitamab-cxix interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
MONJUVI
Look-Alike Drug Names
There is limited information regarding Tafasitamab-cxix Look-Alike Drug Names in the drug label.
Price
References
The contents of this FDA label are provided by the National Library of Medicine.