MONJUVI by is a Prescription medication manufactured, distributed, or labeled by MorphoSys US Inc., Boehringer Ingelheim Pharma GmbH & Co KG, BioReliance Ltd, Pacific BioLabs, Millmount Healthcare Limited (known as PCI Pharma Services), Integrated Commercialization Solutions, LLC, Morphosys US Inc. Drug facts, warnings, and ingredients follow.
MONJUVI is a CD19-directed cytolytic antibody indicated in combination with lenalidomide 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). (1)
For injection: 200 mg of tafasitamab-cxix as lyophilized powder in single-dose vial for reconstitution.(3)
The most common adverse reactions (≥20%) are neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, respiratory tract infection, and decreased appetite. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact MORPHOSYS US INC. at 1-844-667-1992 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Lactation: Advise not to breastfeed. (8.2)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
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 [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
The recommended dose of MONJUVI is 12 mg/kg based on actual body weight administered as an intravenous infusion according to the dosing schedule in Table 1.
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 [see Clinical Studies (14)]. Refer to the lenalidomide prescribing information for lenalidomide dosage recommendations.
|Cycle 1||Days 1, 4, 8, 15 and 22|
|Cycles 2 and 3||Days 1, 8, 15 and 22|
|Cycle 4 and beyond||Days 1 and 15|
MONJUVI should be administered by a healthcare professional with immediate access to emergency equipment and appropriate medical support to manage infusion-related reactions (IRRs) [see Warnings and Precautions (5.1)].
Administer premedications 30 minutes to 2 hours prior to starting MONJUVI infusion to minimize infusion-related reactions [see Warnings and Precautions (5.1)]. Premedications may include acetaminophen, histamine H1 receptor antagonists, histamine H2 receptor antagonists, and/or glucocorticosteroids.
For patients not experiencing infusion-related reactions during the first 3 infusions, premedication is optional for subsequent infusions.
If a patient experiences an infusion-related reaction, administer premedications before each subsequent infusion.
The recommended dosage modifications for adverse reactions are summarized in Table 2.
|Adverse Reaction||Severity||Dosage Modification|
|Infusion-related reactions [see Warnings and Precautions (5.1)]||Grade 2 (moderate)||
|Grade 3 (severe)||
|Grade 4 (life-threatening)||
|Myelosuppression [see Warnings and Precautions (5.2)]||Platelet count of 50,000/ mcL or less||
|Neutrophil count of 1,000/ mcL or less for at least 7 days OR|
Neutrophil count of 1,000/ mcL or less with an increase of body temperature to 100.4°F (38°C) or higher OR
Neutrophil count less than 500/mcL
Reconstitute and dilute MONJUVI prior to infusion.
Do not shake or freeze the reconstituted or diluted infusion solutions.
MONJUVI can cause infusion-related reactions [see Adverse Reactions (6.1)]. 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 chills, 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 [see Dosage and Administration (2.2)]. Monitor patients frequently during infusion. Based on the severity of the infusion-related reaction, interrupt or discontinue MONJUVI [see Dosage and Administration (2.3)]. Institute appropriate medical management.
MONJUVI can cause serious or severe myelosuppression, including neutropenia, thrombocytopenia, and anemia [see Adverse Reactions (6.1)]. 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 [see Dosage and Administration (2.3)]. Refer to the lenalidomide prescribing information for dosage modifications.
Fatal and serious infections, including opportunistic infections, occurred in patients during treatment with MONJUVI and following the last dose [see Adverse Reactions (6.1)].
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.
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 (8.1, 8.3)].
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.
The following clinically significant adverse reactions are described elsewhere in the labeling:
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 [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:
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.
|Grade 3 or 4
|Blood and lymphatic system disorders|
|General disorders and administration site conditions|
|Respiratory, thoracic and mediastinal disorders|
|Respiratory tract infection†||24||4.9|
|Urinary tract infection‡||17||4.9|
|Metabolism and nutrition disorders|
|Musculoskeletal and connective tissue disorders|
Clinically relevant adverse reactions in <10% of patients who received MONJUVI were:
Table 4 summarizes the laboratory abnormalities in L-MIND.
|Grade 3 or 4
|Gamma glutamyl transferase increased||34||5|
|Aspartate aminotransferase increased||20||0|
|Activated partial thromboplastin time increased||46||4.1|
As with all therapeutic proteins, there is the potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assays. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other tafasitamab products may be misleading.
Overall, no treatment-emergent or treatment-boosted anti-tafasitamab antibodies were observed. No clinically meaningful differences in the pharmacokinetics, efficacy, or safety profile of tafasitamab-cxix were observed in 2.5% of 81 patients with relapsed or refractory DLBCL with pre-existing anti-tafasitamab antibodies in L-MIND.
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.
Fetal/Neonatal Adverse Reactions
Immunoglobulin G (IgG) monoclonal antibodies are transferred across the placenta. Based on its mechanism of action, MONJUVI may cause depletion of fetal CD19 positive immune cells. Defer administering live vaccines to neonates and infants exposed to tafasitamab-cxix in utero until a hematology evaluation is completed.
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.
MONJUVI can cause fetal B-cell depletion when administered to a pregnant woman [see Use in Specific Populations (8.1)].
Refer to the prescribing information for lenalidomide for pregnancy testing requirements prior to initiating the combination of MONJUVI with lenalidomide.
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.
The safety and effectiveness of MONJUVI in pediatric patients have not been established.
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%).
Tafasitamab-cxix is a humanized CD19-directed cytolytic monoclonal antibody that contains an IgG1/2 hybrid Fc-domain with 2 amino acid substitutions to modify the Fc-mediated functions of the antibody. It is produced by recombinant DNA technology in mammalian cells (Chinese hamster ovary). Tafasitamab-cxix has a molecular weight of approximately 150 kDa.
MONJUVI (tafasitamab-cxix) for injection is supplied as a sterile, preservative-free, white to slightly yellowish lyophilized powder in a single-dose vial for intravenous use after reconstitution and further dilution. After reconstitution with 5 mL of Sterile Water for Injection, USP, the resulting concentration is 40 mg/mL with a pH of 6.0. Each single-dose vial contains 200 mg tafasitamab-cxix, citric acid monohydrate (3.7 mg), polysorbate 20 (1 mg), sodium citrate dihydrate (31.6 mg) and trehalose dihydrate (378.3 mg).
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.
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.
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.
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).
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.
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).
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:
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). Results are summarized in Table 5.
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).
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Advise patients to contact their healthcare provider if they experience signs and symptoms of infusion-related reactions [see Warnings and Precautions (5.1)].
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 [see Warnings and Precautions (5.2)].
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 [see Warnings and Precautions (5.3)].
Advise women not to breastfeed during treatment with MONJUVI and for at least 3 months after the last dose [see Use in Specific Populations (8.2)].
|This Patient Information has been approved by the U.S. Food and Drug Administration.||Issued: JUL 2020|
|What is MONJUVI?
MONJUVI 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.
It is not known if MONJUVI is safe and effective in children.
|Before you receive MONJUVI, tell your healthcare provider about all of your medical conditions, including if you:
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
|How will I receive MONJUVI?
|What are the possible side effects of MONJUVI?
MONJUVI may cause serious side effects, including:
|These are not all the possible side effects of MONJUVI.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
|General information about the safe and effective use of MONJUVI.
Medicines are sometimes prescribed for purposes other than those listed in this Patient Information. If you would like more information about MONJUVI, talk with your healthcare provider. You can ask your healthcare provider for information about MONJUVI that is written for health professionals.
|What are the ingredients in MONJUVI?
Active ingredient: tafasitamab-cxix.
Inactive ingredients: citric acid monohydrate, polysorbate 20, sodium citrate dihydrate, and trehalose dihydrate.
Manufactured by: MORPHOSYS US INC., Boston, MA 02210, U.S. License No. 2152,
Marketed by: MORPHOSYS US INC. and INCYTE Corporation.
MONJUVI is a registered trademark of MorphoSys AG. © 2020 MorphoSys AG. All rights reserved.
For more information call MorphoSys US Inc., at 1-844-667-1992 or go to www.MONJUVI.com.
tafasitamab-cxix injection, powder, lyophilized, for solution
|Labeler - MorphoSys US Inc. (100556743)|
|Boehringer Ingelheim Pharma GmbH & Co KG||340700520||API MANUFACTURE(73535-208) , MANUFACTURE(73535-208) , ANALYSIS(73535-208) , PACK(73535-208)|
|Millmount Healthcare Limited (known as PCI Pharma Services)||989237516||LABEL(73535-208) , PACK(73535-208)|
|Integrated Commercialization Solutions, LLC||832820588||REPACK(73535-208)|
|Morphosys US Inc||100556743||ANALYSIS(73535-208)|