Tafasitamab, an anti-CD19 monoclonal antibody, is an antineoplastic agent.1
Tafasitamab-cxix is used in combination with lenalidomide for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low-grade lymphoma, in those who are not candidates for autologous stem cell transplant.1, 2 The accelerated approval of tafasitamab-cxix for this indication is based on overall response rate.1 Continued approval for this indication may be contingent on verification and description of clinical benefit of tafasitamab-cxix in confirmatory studies.1 The drug has been designated an orphan drug by FDA for the treatment of this cancer.5
The current indication for tafasitamab-cxix (in combination with lenalidomide initially followed by tafasitamab-cxix monotherapy) for the treatment of relapsed or refractory DLBCL not otherwise specified is based principally on results of an open-label, multicenter, noncomparative phase 2 study (L-MIND) in 71 adults with relapsed or refractory DLBCL previously treated with 1-3 systemic therapies who were not candidates for high-dose chemotherapy and autologous stem cell transplantation.1, 2 Prior systemic therapy must have included an anti-CD20 monoclonal antibody.1 In this study, patients received tafasitamab-cxix in combination with lenalidomide (25 mg orally on days 1-21) for a maximum of 12 cycles followed by single-agent tafasitamab-cxix until disease progression or unacceptable toxicity occurred.1 Treatment cycles were repeated every 28 days.1 Tafasitamab-cxix 12 mg/kg was administered by IV infusion on days 1, 4, 8, 15, and 22 during cycle 1 followed by 12 mg/kg by IV infusion on days 1, 8, 15, and 22 during cycles 2 and 3.1, 2 For subsequent cycles, the same dosage of tafasitamab-cxix was administered on days 1 and 15 of each 28-day cycle.1, 2 The primary measure of efficacy was best overall response rate (as assessed by an independent review committee) using the International Working Group (IWG) response criteria.1 The patients had a median age of 71 years and had received a median of 2 prior therapies for their disease; 100% had received prior anti-CD20-containing therapy, 45% were refractory to their last prior therapy, 42% were refractory to rituximab, and 13% had undergone prior autologous stem cell transplantation.1 The primary reasons patients were not candidates for autologous stem cell transplantation included age, refractoriness to salvage chemotherapy, comorbidities, and patient preference.1 The overall response rate was 55% with a median response duration of 21.7 months; complete response was achieved in 37% of patients.1
To minimize the risk of infusion-related reactions associated with tafasitamab, premedication with an antihistamine, acetaminophen, histamine H2-receptor antagonist, and/or corticosteroid should be administered 30 minutes to 2 hours prior to infusion of tafasitamab.1 If infusion-related events do not occur during the first 3 infusions of tafasitamab, the manufacturer states that premedication is not necessary for subsequent infusions.1 Patients who experience an infusion-related reaction should receive premedications prior to subsequent infusions of tafasitamab.1 (See Infusion-related Effects under Cautions.)
Tafasitamab should be administered only in settings where emergency equipment and appropriate medical support is available for management of potential infusion-related reactions.1 (See Infusion-related Effects under Cautions.)
Tafasitamab-cxix is available only from designated specialty distributors.4 The manufacturer should be contacted for additional information.4
Tafasitamab-cxix is administered by IV infusion.1 Tafasitamab-cxix should not be administered simultaneously through the same IV line with any other drug.1
The manufacturer states that no incompatibilities between tafasitamab-cxix and infusion containers made of PVC, polypropylene, polyethylene, polyethylenterephthalate, or glass and administration sets made of polyurethane or PVC have been observed.1
Based on the indicated dosage of tafasitamab-cxix, the appropriate number of vials of the drug should be reconstituted.1
Each vial labeled as containing 200 mg of tafasitamab-cxix is reconstituted by adding 5 mL of sterile water for injection to provide a solution containing 40 mg/mL.1 The diluent should be directed toward the inside wall of the vial.1 The vial should then be gently swirled until complete dissolution of the powder occurs.1 The vial should not be shaken or swirled vigorously.1 Dissolution may take up to 5 minutes.1 The resulting solution should be inspected visually for particulate matter and discoloration prior to dilution.1 The solution should be colorless to slightly yellow; the drug should be discarded if the solution is cloudy, discolored, or contains a precipitate.1
The reconstituted tafasitamab-cxix solution may be diluted immediately or stored at 2-8ºC or 20-25ºC for use within 12 hours.1 The reconstituted solution should not be frozen and should be protected from light until use.1
For preparation of the final diluted tafasitamab-cxix solution for infusion, a volume equivalent to the volume of the appropriate dose of tafasitamab-cxix should be withdrawn from an infusion bag containing 250 mL of 0.9% sodium chloride injection and discarded; the appropriate dose of tafasitamab-cxix solution should then be withdrawn from the vial(s) and slowly added to the infusion bag to yield a final concentration of 2-8 mg/mL.1 The final diluted tafasitamab-cxix solution for infusion should be mixed by gentle inversion and should not be shaken.1 Any partially used vials should be discarded.1 The resulting solution should be inspected visually for particulate matter and discoloration prior to administration.1
The final diluted tafasitamab-cxix solution for infusion may be administered immediately or stored at 2-8ºC for use within 18 hours; alternatively, the diluted solution may be stored at 20-25ºC for use within 12 hours (including infusion time).1 The solution for infusion should not be frozen and should be protected from light until use.1
The initial tafasitamab-cxix dose (cycle 1 day 1) should be infused IV at an initial rate of 70 mL/hour for the first 30 minutes and then the infusion rate may be increased so the infusion is administered within 1.5-2 hours.1
Subsequent IV infusions of tafasitamab-cxix may be administered over 1.5-2 hours.1
For the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified in adults who are not candidates for autologous stem cell transplant, tafasitamab-cxix is administered in combination with lenalidomide in 28-day cycles for a maximum of 12 cycles followed by single-agent tafasitamab-cxix administered until disease progression or unacceptable toxicity occurs.1, 2
The recommended adult dosage of tafasitamab-cxix during cycle 1 is 12 mg/kg by IV infusion on days 1, 4, 8, 15, and 22.1 For cycles 2 and 3, the same dosage of tafasitamab-cxix (12 mg/kg) is administered on days 1, 8, 15, and 22; for cycle 4 and beyond, the same dosage is administered on days 1 and 15.1 In the L-MIND study, lenalidomide (25 mg orally once daily) was administered on days 1-21 of each 28-day cycle for a maximum of 12 cycles.1
Dosage Modification for Toxicity
Clinicians should consult the respective manufacturers' labelings or published protocols for information on the dosage adjustments of other antineoplastic agents used in combination regimens.1
If grade 2-4 infusion-related reactions occur, the tafasitamab infusion should be interrupted and appropriate treatment and supportive care should be provided.1
If grade 2 infusion-related reactions occur, the infusion should be interrupted.1 Once the reaction has resolved or improved to grade 1, the infusion may be resumed at a rate no more than 50% of the previous infusion rate.1 If the patient does not experience an infusion-related reaction within one hour of resuming the infusion and vital signs are stable, the infusion rate may be increased as tolerated every 30 minutes to the previous infusion rate.1
If grade 3 infusion-related reactions occur, the infusion should be interrupted.1 Once the reaction has resolved or improved to grade 1, the infusion may be resumed at a rate no more than 25% of the previous infusion rate.1 If the patient does not experience an infusion-related reaction within one hour of resuming the infusion and vital signs are stable, the infusion rate may be increased as tolerated every 30 minutes to a maximum of 50% of the previous infusion rate.1 If the infusion-related reaction recurs, the infusion should be immediately discontinued.1
If grade 4 infusion-related reactions occur, the infusion should be interrupted immediately and tafasitamab therapy should be permanently discontinued.1
For platelet count 50,000/mm3 or less, tafasitamab and lenalidomide therapy should be withheld and complete blood cell counts (CBCs) should be monitored weekly until platelet count reaches or exceeds 50,000/mm3.1 When platelet count reaches or exceeds 50,000/mm3, tafasitamab may then be resumed at the same dosa however, the dosage of lenalidomide should be reduced.1
For neutrophil count 1000/mm3 or less lasting at least 7 days, tafasitamab and lenalidomide therapy should be withheld and CBCs should be monitored weekly until neutrophil count reaches or exceeds 1000/mm3.1 When neutrophil count reaches or exceeds 1000/mm3, tafasitamab may be resumed at the same dosa however, the dosage of lenalidomide should be reduced.1
For neutrophil count less than 500/mm3, tafasitamab and lenalidomide therapy should be withheld and CBCs should be monitored weekly until neutrophil count reaches or exceeds 1000/mm3.1 When neutrophil count reaches or exceeds 1000/mm3, tafasitamab may be resumed at the same dosa however, the dosage of lenalidomide should be reduced.1
If febrile neutropenia occurs (temperature of 38ºC or higher and neutrophil count 1000/mm3 or less), tafasitamab and lenalidomide therapy should be withheld and CBCs should be monitored weekly until neutrophil count reaches or exceeds 1000/mm3.1 When neutrophil count reaches or exceeds 1000/mm3, tafasitamab may be resumed at the same dosa however, the dosage of lenalidomide should be reduced.1
The manufacturer makes no specific dosage recommendations for geriatric patients or for those with renal or hepatic impairment.1
When tafasitamab is used in combination with lenalidomide, the usual cautions, precautions, and contraindications associated with lenalidomide must be considered in addition to those associated with tafasitamab.1 For further information regarding warnings and precautions associated with lenalidomide, see Cautions in Lenalidomide 10:00.
Infusion-related reactions have been reported in patients receiving tafasitamab.1 In the principal efficacy study (L-MIND), infusion-related reactions occurred in 6% of patients receiving tafasitamab-cxix and were managed by temporary interruption of the infusion and/or symptomatic and supportive therapy; 80% of infusion-related reactions occurred during cycle 1 or 2.1 Signs or symptoms of such reactions may include chills, flushing, dyspnea, and hypertension.1
To minimize the risk of infusion-related reactions, patients receiving tafasitamab should be premedicated with an antihistamine, acetaminophen, histamine H2-receptor antagonist, and/or a corticosteroid prior to administration of the drug.1 (See General under Dosage and Administration.) Patients should be monitored frequently during infusions of the drug for manifestations of infusion-related reactions.1 Temporary interruption of the tafasitamab infusion or discontinuance of tafasitamab therapy may be necessary in patients experiencing an infusion-related reaction and appropriate treatment and supportive care should be provided.1 (See Dosage Modification for Toxicity under Dosage and Administration.)
Adverse hematologic effects (i.e., anemia, thrombocytopenia, neutropenia) have been reported in patients receiving tafasitamab.1, 2 In the L-MIND study, grade 3 or 4 neutropenia or thrombocytopenia occurred in 50 or 18%, respectively, of patients receiving tafasitamab-cxix, and grade 3 anemia occurred in 7% of patients receiving the drug.1 In patients who developed neutropenia, discontinuance of tafasitamab-cxix therapy was required in 3.7% of patients.1
Complete blood cell counts (CBCs) should be monitored prior to each treatment cycle and as clinically indicated.1 If neutropenia occurs, patients should be monitored for signs of infection and use of granulocyte colony-stimulating factors (G-CSFs) to treat neutropenia may be considered.1 Temporary interruption of tafasitamab may be necessary in patients experiencing hematologic toxicity during therapy with the drug.1 (See Dosage Modification for Toxicity under Dosage and Administration.) Clinicians should consult the manufacturer's labeling for lenalidomide for information on dosage adjustments of the drug.1
Fatal and serious infections, including opportunistic infections, have been reported in patients during tafasitamab therapy and following the last dose of the drug.1, 2 In the L-MIND study, infections occurred in 73% of patients receiving tafasitamab-cxix; grade 3 or higher infections occurred in 30% of patients receiving the drug.1 The most frequent infections were respiratory tract infection, urinary tract infection, bronchitis, nasopharyngitis, and pneumonia.1 Infection-related deaths occurred in 2.5% of patients receiving tafasitamab-cxix.1
Patients should be monitored for signs of infection during tafasitamab therapy; if an infection develops, the infection should be managed as clinically indicated.1
Fetal/Neonatal Morbidity and Mortality
Tafasitamab may cause fetal harm in humans based on its mechanism of action.1 There are no available data regarding use or risks of tafasitamab in pregnant women.1 Animal reproduction studies have not been performed to date with the drug.1 The possibility that B-cell depletion may occur in infants born to women who received tafasitamab during pregnancy should be considered; B-cell depletion can affect vaccine immune responses in infants.1 Clinicians should consult a hematologist prior to administering live vaccines to neonates and infants born to mothers treated with tafasitamab during pregnancy.1
When tafasitamab is administered in combination with lenalidomide, clinicians must consider that lenalidomide is contraindicated in pregnant women.1 The usual cautions, precautions, and contraindications associated with lenalidomide must be considered in addition to those associated with tafasitamab.1 For further information regarding warnings and precautions associated with lenalidomide, see Cautions in Lenalidomide 10:00.
Pregnancy should be avoided during tafasitamab therapy.1 Women of reproductive potential should be advised to use effective contraceptive methods while receiving tafasitamab and for at least 3 months after the last dose.1 Patients should be apprised of the potential hazard to the fetus if tafasitamab is used during pregnancy.1
There is potential for immunogenicity with the use of therapeutic proteins such as tafasitamab.1 In clinical trials, no treatment-emergent or treatment-boosted anti-tafasitamab antibodies were observed.1 In the principal efficacy study, no clinically meaningful differences in the pharmacokinetics, efficacy, or safety of tafasitamab were observed in 2.5% of 81 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) with pre-existing anti-tafasitamab antibodies.1
There are no adequate and well-controlled studies of tafasitamab in pregnant women.1 Animal reproduction studies have not been performed to date with the drug.1
When tafasitamab is administered in combination with lenalidomide, clinicians must consider that lenalidomide is contraindicated in pregnant women.1 (See Combination Therapy under Cautions.)
It is not known whether tafasitamab is distributed into human milk; however, maternal IgG is known to be present in human milk.1 The effects of the drug on nursing infants or on the production of milk are unknown.1
Because of the potential for adverse reactions to tafasitamab in nursing infants, women should be advised not to nurse while receiving the drug and for at least 3 months after the last dose.1
Safety and efficacy of tafasitamab have not been established in pediatric patients.1
Clinical studies of tafasitamab-cxix did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger adults.1 In the principal efficacy study evaluating tafasitamab-cxix in combination with lenalidomide, 72% of patients with relapsed or refractory DLBCL were 65 years of age or older and 38% were 75 years of age or older.1 Serious adverse effects occurred more frequently in geriatric patients compared to younger adults (57 versus 39%, respectively).1
Pharmacokinetics of tafasitamab do not appear to be altered in patients with mild hepatic impairment (total bilirubin concentration not exceeding the upper limit of normal [ULN] with AST concentration exceeding the ULN, or total bilirubin concentration 1-1.5 times the ULN with any AST concentration).1
The pharmacokinetic profile of tafasitamab has not been established in patients with moderate to severe hepatic impairment (total bilirubin concentration exceeding 1.5 times the ULN with any AST concentration).1
Pharmacokinetics of tafasitamab do not appear to be altered in patients with mild to moderate renal impairment (creatinine clearance 30-89 mL/minute).1
The pharmacokinetic profile of tafasitamab has not been established in patients with severe renal impairment to end-stage renal disease (creatinine clearance less than 30 mL/minute).1
Adverse effects reported in 20% or more of patients receiving tafasitamab-cxix in combination with lenalidomide for the treatment of relapsed or refractory DLBCL include neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, respiratory tract infection, and decreased appetite.1
Concomitant use of lenalidomide and tafasitamab-cxix had no clinically important effect on pharmacokinetics of tafasitamab.1
Tafasitamab, a recombinant humanized anti-CD19 monoclonal antibody, is an antineoplastic agent.1 The drug is an Fc-modified IgG1-IgG2 kappa immunoglobulin produced by recombinant DNA technology in mammalian cell (Chinese hamster ovary) culture.1, 2, 3, 6 Tafasitamab binds specifically to the antigen CD19, a cell-surface antigen expressed on malignant B-lymphocytes, including diffuse large B-cell lymphoma (DLBCL) cells.1 CD19 is critically involved in enhancing B-cell receptor signaling and activation of downstream signaling pathways (i.e., Src family, Ras family, Bcr-Abl, BTK, Vav, Grb2, PI3K) that play a crucial role in tumor cell proliferation and survival.1, 7 Following binding of tafasitamab to antigen CD19, the Fc domain triggers host immune responses (i.e., antibody-dependent cell-mediated cytotoxicity [ADCC], antibody-dependent cellular phagocytosis [ADCP]) causing lysis of the B-cells.1 In vitro in DLBCL tumor cells, the combination of tafasitamab and lenalidomide increased ADCC activity compared with either drug alone.1
In patients with relapsed or refractory DLBCL, peripheral blood B-cell counts are reduced by 97% after 8 days of tafasitamab treatment and reach a nadir (100% reduction) within 16 weeks of treatment.1 As a human IgG monoclonal antibody, the drug is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.3 The terminal half-life of tafasitamab is approximately 17 days.1
The pharmacokinetics of tafasitamab do not appear to be affected by age (16-90 years) and sex.1 Dosage of tafasitamab is based on body weight because clearance and volume of distribution of the drug are expected to increase with increasing body weight.1
Advise the patient to read the FDA-approved patient labeling (Patient Information).1
Advise patients to contact their clinician if they experience signs and symptoms of infusion-related reactions.1
Inform patients about the risk of myelosuppression.1 Advise patients to immediately contact their clinician for a fever of 38°C or greater or signs or symptoms of bruising or bleeding.1 Advise patients of the need for periodic monitoring of blood counts.1
Inform patients about the risk of infections.1 Advise patients to immediately contact their clinician for a fever of 38°C or greater or signs or symptoms of infection.1
Advise pregnant women of the potential risk to a fetus.1 Advise females of reproductive potential to inform their clinician of a known or suspected pregnancy.1
Advise females of reproductive potential to use effective contraception during treatment with tafasitamab and for at least 3 months after the last dose.1
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.1 Lenalidomide is only available through a Risk Evaluation and Mitigation Strategy (REMS) program.1
Advise women not to breast-feed during treatment with tafasitamab and for at least 3 months after the last dose.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Additional Information
Overview® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Tafasitamab-cxix can only be obtained through select specialty distributors.4
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | For injection, for IV infusion only | 200 mg | MorphoSys US |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions May 24, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. MorphoSys US Inc. Monjuvi® (tafasitamab-cxix) for injection prescribing information. Boston, MA; 2020 Jul.
2. Salles G, Duell J, González Barca E et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol . 2020; 21:978-988. [PubMed 32511983]
3. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 761163Orig1s000: Multi-discipline review. From FDA website. [Web]
4. MorphoSys US Inc. From Monjuvi® (tafasitamab-cxix) for healthcare professionals website. Accessed 4 Dec 2020. [Web]
5. Food and Drug Administration. FDA Application: Search orphan drug designations and approvals. Silver Spring, MD. From FDA web site. [Web]
6. Kellner C, Zhukovsky EA, Pötzke A et al. The Fc-engineered CD19 antibody MOR208 (XmAb5574) induces natural killer cell-mediated lysis of acute lymphoblastic leukemia cells from pediatric and adult patients. Leukemia . 2013; 27:1595-8. [PubMed 23277329]
7. Jurczak W, Zinzani PL, Gaidano G et al. Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. Ann Oncol . 2018; 29:1266-1272. [PubMedCentral][PubMed 29444231]