Class: Antineoplastic Agents
Chemical Name: Anti-(human CD19 antigen) (human-Mus musculus monoclonal MOR00208 heavy chain), disulfide with human-Mus musculus monoclonal MOR00208 k-chain dimer, immunoglobulin G1-G2-kappa
Molecular Formula: C6550H10092N1724O2048S52
CAS Number: 1422527-84-1
Antineoplastic agent; anti-CD19 monoclonal antibody.
Uses for Tafasitamab-cxix
Diffuse Large B-cell Lymphoma (DLBCL)
Used in combination with lenalidomide for the treatment of relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low-grade lymphoma, in those who are not candidates for autologous stem cell transplant (designated an orphan drug by FDA for this use).
Accelerated approval based on overall response rate; continued approval may be contingent on verification and description of clinical benefit in confirmatory studies.
Tafasitamab-cxix Dosage and Administration
To minimize risk of infusion-related reactions, premedicate with an antihistamine, acetaminophen, histamine H2-receptor antagonist, and/or corticosteroid 30 minutes to 2 hours prior to infusion of tafasitamab. Premedication is not necessary for subsequent infusions if infusion-related events do not occur during the first 3 infusions of the drug. If infusion-related reactions occur, premedicate prior to subsequent infusions of the drug.
Administer only in settings where emergency equipment and appropriate medical support is available. (See Infusion-related Effects under Cautions.)
Obtain through designated specialty distributors.
Administer by IV infusion. Do not infuse simultaneously through the same IV line with any other drug.
Reconstitute appropriate number of vials containing 200 mg of tafasitamab-cxix to achieve desired dose.
Reconstitute each vial containing 200 mg of tafasitamab-cxix with 5 mL of sterile water for injection to provide a solution containing 40 mg/mL. Direct diluent toward the wall of the vial. Gently swirl vial; dissolution of the powder may take up to 5 minutes. Do not shake or vigorously swirl vial.
Reconstituted solution should be colorless to slightly yellow. Discard solution if it is cloudy, discolored, or contains a precipitate.
Dilute reconstituted solution immediately or store at 2–8ºC or 20–25ºC for use within 12 hours. Do not freeze; protect from light until use.
Withdraw and discard volume equivalent to the volume of the appropriate dose of tafasitamab-cxix from an infusion bag containing 250 mL of 0.9% sodium chloride injection.
To prepare final diluted solution for infusion, slowly add appropriate dose of reconstituted tafasitamab-cxix solution to the infusion bag containing 0.9% sodium chloride injection to yield a final concentration of 2–8 mg/mL. Mix by gentle inversion; do not shake.
Discard any partially used vials. Inspect visually for particulate matter and discoloration prior to administration.
Administer diluted infusion solution immediately or store at 2–8ºC for use within 18 hours or at 20–25ºC for use within 12 hours (including infusion time). Do not freeze diluted solution; protect from light until use.
Rate of Administration
Administer initial dose (cycle 1 day 1) by IV infusion at an initial rate of 70 mL/hour for the first 30 minutes; may increase infusion rate so infusion is administered within 1.5–2 hours.
Subsequent IV infusions may be administered over 1.5–2 hours.
12 mg/kg by IV infusion in combination with lenalidomide (25 mg orally once daily on days 1–21) for a maximum of 12 cycles followed by 12 mg/kg of tafasitamab-cxix by IV infusion as monotherapy until disease progression or unacceptable toxicity occurs. Treatment cycles are repeated every 28 days.
For cycle 1, tafasitamab-cxix is administered on days 1, 4, 8, 15, and 22.
For cycles 2 and 3, tafasitamab-cxix is administered on days 1, 8, 15, and 22.
For cycles 4 and beyond, tafasitamab-cxix is administered on days 1 and 15.
Dosage Modification for Toxicity
Consult respective manufacturers' labelings or published protocols for information on the dosage adjustments of other antineoplastic agents used in combination regimens.
For grade 2–4 infusion-related reactions, interrupt infusion and provide appropriate treatment and supportive care.
For grade 2 infusion-related reactions, interrupt infusion; may resume infusion at no more than 50% of the previous infusion rate once reaction resolves or improves to grade 1. If no infusion-related reaction occurs within one hour of resuming infusion and vital signs are stable, may increase infusion rate, as tolerated, every 30 minutes to the previous infusion rate.
For grade 3 infusion-related reactions, interrupt infusion; may resume infusion at no more than 25% of the previous infusion rate once reaction resolves or improves to grade 1. If no infusion-related reaction occurs within one hour of resuming the infusion and vital signs are stable, may increase infusion rate, as tolerated, every 30 minutes to a maximum of 50% of previous infusion rate. If infusion-related reaction recurs, immediately discontinue infusion.
For grade 4 infusion-related reactions, immediately interrupt infusion and permanently discontinue drug.
For platelet count ≤50,000/mm3, withhold tafasitamab and lenalidomide and monitor CBCs weekly until platelet count ≥50,000/mm3; may then resume tafasitamab at same dosage and lenalidomide at reduced dosage. Consult prescribing information for lenalidomide for dosage modification recommendations.
For neutrophil count ≤1000/mm3 lasting ≥7 days, withhold tafasitamab and lenalidomide and monitor CBCs weekly until neutrophil count ≥1000/mm3; may then resume tafasitamab at same dosage and lenalidomide at reduced dosage. Consult prescribing information for lenalidomide for dosage modification recommendations.
For neutrophil count <500/mm3, withhold tafasitamab and lenalidomide and monitor CBCs weekly until neutrophil count ≥1000/mm3; may then resume tafasitamab at same dosage and lenalidomide at reduced dosage. Consult prescribing information for lenalidomide for dosage modification recommendations.
If febrile neutropenia occurs (temperature of ≥38ºC and neutrophil count ≤1000/mm3), withhold tafasitamab and lenalidomide and monitor CBCs weekly until neutrophil count ≥1000/mm3; may then resume tafasitamab at same dosage and lenalidomide at reduced dosage. Consult prescribing information for lenalidomide for dosage modification recommendations.
Maximum of 12 cycles when used in combination with lenalidomide.
No specific dosage recommendations. (See Hepatic Impairment under Cautions.)
No specific dosage recommendations. (See Renal Impairment under Cautions.)
No specific dosage recommendations. (See Geriatric Use under Cautions.)
Cautions for Tafasitamab-cxix
When used in combination with lenalidomide, consider the usual cautions, precautions, and contraindications associated with lenalidomide in addition to those associated with tafasitamab.
Infusion-related reactions (e.g., chills, flushing, dyspnea, hypertension) reported. Infusion-related reactions generally occur during cycle 1 or 2.
To minimize risk of infusion-related reactions, premedicate with an antihistamine, acetaminophen, histamine H2-receptor antagonist, and/or corticosteroid prior to administration of drug. Monitor patients frequently during infusions. Temporary interruption of 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. (See Dosage Modification for Toxicity under Dosage and Administration.)
Adverse hematologic effects (i.e., anemia, thrombocytopenia, neutropenia) reported.
Monitor CBCs prior to each treatment cycle and as clinically indicated. If neutropenia occurs, monitor for signs of infection and consider treatment with a granulocyte colony-stimulating factor (G-CSF). Temporary interruption of tafasitamab may be necessary. (See Dosage Modification for Toxicity under Dosage and Administration.)
Fatal and serious infections (respiratory tract infection, urinary tract infection, bronchitis, nasopharyngitis, pneumonia), including opportunistic infections, reported during tafasitamab therapy and following the last dose of the drug. In the L-MIND study, infections occurred in 73% of patients receiving tafasitamab-cxix and grade 3 or higher infections occurred in 30% of patients receiving the drug.
Monitor for signs of infection during therapy. If an infection develops, manage as clinically indicated.
Fetal/Neonatal Morbidity and Mortality
May cause fetal harm based on its mechanism of action. B-cell depletion may occur in infants born to women who received tafasitamab during pregnancy; B-cell depletion can affect vaccine immune responses in infants.
Consult a hematologist prior to administering live vaccines to neonates and infants born to mothers treated with tafasitamab during pregnancy.
When used in combination with lenalidomide, consider that lenalidomide is contraindicated in pregnant women.
Avoid pregnancy during therapy. Women of reproductive potential should use effective contraceptive methods while receiving the drug and for ≥3 months after the last dose. If used during pregnancy, apprise patient of potential fetal hazard.
Potential for immunogenicity. No treatment-emergent or treatment-boosted anti-tafasitamab antibodies observed in clinical trials.
Presence of anti-tafasitamab antibodies at baseline does not appear to affect pharmacokinetics, efficacy, or safety of tafasitamab.
May cause fetal harm. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
When used in combination with lenalidomide, consider that lenalidomide is contraindicated in pregnant women.
Not known whether tafasitamab is distributed into milk, affects nursing infants, or affects milk production. Discontinue nursing during therapy and for ≥3 months after the last dose.
Safety and efficacy not established.
Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults. In the principal efficacy study, serious adverse effects occurred more frequently in geriatric patients compared with younger adults.
Pharmacokinetics do not appear to be altered by mild hepatic impairment (total bilirubin concentration not exceeding the ULN with AST concentration exceeding the ULN, or total bilirubin concentration 1–1.5 times the ULN with any AST concentration).
Not studied in patients with moderate to severe hepatic impairment (total bilirubin concentration >1.5 times ULN with any AST concentration).
Pharmacokinetics do not appear to be altered by mild to moderate renal impairment (Clcr 30–89 mL/minute).
Not studied in patients with severe renal impairment to end-stage renal disease (Clcr <30 mL/minute).
Common Adverse Effects
Combination therapy with lenalidomide: Neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, respiratory tract infection, decreased appetite.
Interactions for Tafasitamab-cxix
No clinically important effect on pharmacokinetics of tafasitamab
In patients with relapsed or refractory DLBCL, peripheral blood B-cell counts reduced by 97% after 8 days of tafasitamab and reach a nadir (100% reduction) within 16 weeks of treatment.
Mild hepatic impairment: No clinically important effect on pharmacokinetics of tafasitamab.
Moderate to severe hepatic impairment: Not studied.
Mild to moderate renal impairment: No clinically important effect on pharmacokinetics of tafasitamab.
Severe renal impairment to end-stage renal disease: Not studied.
Age (16–90 years) and sex do not appear to have meaningful effects on pharmacokinetics of tafasitamab.
Not known whether distributed into human milk.
Volume of distribution increases with increasing body weight.
Expected to degrade into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.
Approximately 17 days.
Clearance increases with increasing body weight.
Powder for Injection
2–8°C in original carton to protect from light. Do not freeze or shake.
May store reconstituted drug in vial at 2–8ºC or 20–25ºC for use within 12 hours after reconstitution. Protect from light until use. Do not freeze or shake.
May store infusion solution at 2–8 or 20–25ºC for use within 18 or 12 hours (including infusion time), respectively, after dilution. Do not freeze or shake.
For information on systemic interactions resulting from concomitant use, see Interactions.
No incompatibilities observed with PVC, polypropylene, polyethylene, polyethylenterephthalate, or glass infusion containers and polyurethane or PVC administration sets.
Sodium chloride 0.9%
Antineoplastic agent; a recombinant humanized anti-CD19 monoclonal antibody.
Fc-modified IgG1-IgG2 kappa immunoglobulin produced by recombinant DNA technology in mammalian cell (Chinese hamster ovary) culture.
Binds specifically to antigen CD19, a cell-surface antigen 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.
Following binding to antigen CD19, host immune responses (i.e., antibody-dependent cell-mediated cytotoxicity [ADCC], antibody-dependent cellular phagocytosis [ADCP]) cause lysis of B-cells.
In vitro in DLBCL tumor cells, combination of tafasitamab and lenalidomide increases ADCC activity compared with either drug alone.
Advice to Patients
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Advise patients to contact their clinician if they experience signs and symptoms of infusion-related reactions.
Inform patients about the risk of myelosuppression. Advise patients to immediately contact their clinician for a fever of ≥38°C or signs or symptoms of bruising or bleeding. Advise patients of the need for periodic monitoring of blood counts.
Inform patients about the risk of infections. Advise patients to immediately contact their clinician for a fever of 38°C or greater or signs or symptoms of infection.
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their clinician of a known or suspected pregnancy.
Advise females of reproductive potential to use effective contraception during treatment with tafasitamab 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 Risk Evaluation and Mitigation Strategy (REMS) program.
Advise women not to breast-feed during treatment with tafasitamab and for at least 3 months after the last dose.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
Importance of informing patients of other important precautionary information. (See Cautions.)
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.
Distribution of tafasitamab-cxix is restricted.
For injection, for IV infusion only
AHFS DI Essentials™. © Copyright 2021, Selected Revisions May 24, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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