In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms of action, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs.

On July 31, 2020, tafasitamab-cxix, a CD19-directed cytolytic antibody, was granted accelerated approval for use in combination with lenalidomide for adults 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 transplantation (ASCT).^1,2

Supporting Efficacy Data

The efficacy of tafasitamab with lenalidomide was evaluated in the multicenter, single-arm L-MIND trial (ClinicalTrials.gov identifier NCT02399085).² In the trial, 81 patients received tafasitamab at 12 mg/kg intravenously (IV) with lenalidomide at 25 mg orally on days 1 to 21 of each 28-day cycle for a maximum of 12 cycles, followed by tafasitamab as monotherapy. Tafasitamab was administered on days 1, 4, 8, 15, and 22 of cycle 1; days 1, 8, 15, and 22 of cycles 2 and 3; and days 1 and 15 of cycle 4 and subsequent cycles, with treatment continued until disease progression or unacceptable toxicity.

Among the 71 patients who received the combination therapy, all had DLBCL that was confirmed by central laboratory testing. The median number of prior therapies was two, with 49% having had one and 51% two to four prior lines; 45% were refractory to their last prior therapy and 42% were refractory to rituximab; and 13% had received prior ASCT.

Efficacy was based on best overall response rate and response duration as assessed by an independent review committee in the 71 patients with centrally confirmed DLBCL. An objective response was observed in 39 patients (55%), with a complete response in 37%. The median response duration was 21.7 months (range = 0–24 months).

How It Works

Tafasitamab 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 DLBCL. Upon binding to CD19, tafasitamab mediates B-cell lysis through apoptosis and immune effector mechanisms, including antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. In studies conducted in vitro in DLBCL tumor cells, tafasitamab in combination with lenalidomide resulted in increased antibody-dependent cellular cytotoxicity compared with tafasitamab or lenalidomide alone.

How It Is Used

The recommended tafasitamab dose is 12 mg/kg as an IV infusion. Tafasitamab is administered in combination with lenalidomide at 25 mg for a maximum of 12 28-day cycles and then continued as monotherapy until disease progression or unacceptable toxicity. The dosing schedule is days 1, 4, 8, 15, and 22 of cycle 1; days 1, 8, 15, and 22 of cycle 2 and 3; and days 1 and 15 of cycle 4 and subsequent cycles. Lenalidomide prescribing information should be consulted for lenalidomide dosage recommendations and modifications for adverse reactions.

Tafasitamab should be administered by a health-care professional with immediate access to emergency equipment and appropriate medical support to manage infusion-related reactions. Premedication should be administered 30 minutes to 2 hours prior to starting infusion to minimize infusion-related reactions; premedications may include acetaminophen, histamine 1–receptor antagonists, histamine 2–receptor antagonists, and/or corticosteroids. For patients not experiencing infusion-related reactions during the first three infusions, premedication is optional for subsequent infusions.

For the first infusion, an infusion rate of 70 mL/h should be used for the first 30 minutes. The rate should subsequently be increased so the infusion is administered within 1.5 to 2.5 hours. All subsequent infusions can be administered within 1.5 to 2 hours. Product labeling provides detailed instructions on dosage modification for and management of adverse reactions, including infusion-related reactions and myelosuppression.

Safety Profile

Among all 81 patients who received tafasitamab in the L-MIND trial, 57% were exposed for at least 6 months; 42%, for more than 1 year; and 24%, for more than 2 years.

The most common adverse events of any grade (≥ 20%) were neutropenia (51%), fatigue (38%), anemia (36%), diarrhea (36%), thrombocytopenia (31%), cough (26%), pyrexia (24%), peripheral edema (24%), respiratory tract infection (24%), and decreased appetite (22%). The most common grade 3 or 4 adverse events included neutropenia (49%), thrombocytopenia (17%), febrile neutropenia (12%), anemia (7%), respiratory tract infection (5%), and urinary tract infection (5%). Apart from myelosuppression, the most common grade 3 or 4 laboratory abnormality was increased urate.

Serious adverse events occurred in 52% of patients, the most common being infections, including pneumonia and febrile neutropenia. Dosage interruptions of tafasitamab or lenalidomide due to an adverse event occurred in 69% of patients; dosage interruption of tafasitamab due to an adverse event occurred in 65%, the most frequent causes being blood and lymphatic system disorders (41%) and infections (27%).

Adverse events led to discontinuation of tafasitamab or lenalidomide in 25% of patients and to discontinuation of tafasitamab in 15%, the most common causes being infections; nervous system disorders; and respiratory, thoracic, and mediastinal disorders. Fatal adverse events occurred in 5% of patients, including cerebrovascular accident, respiratory failure, progressive multifocal leukoencephalopathy, and sudden death.

Tafasitamab has warnings/precautions for infusion-related reactions, myelosuppression, infections (including bacterial, fungal, and viral infections during and following treatment), and embryofetal toxicity. Patients should be monitored frequently during infusion, and infusion should be interrupted or discontinued based on the severity of infusion-related reactions. Complete blood cell counts should be monitored and myelosuppression managed with dose modification and growth factor support; treatment should be interrupted or discontinued based on the severity of myelosuppression. Patients should be monitored for infection and advised not to breastfeed while receiving tafasitamab. 

REFERENCES

1. U.S. Food and Drug Administration: FDA grants accelerated approval to tafasitamab-cxix for diffuse large B-cell lymphoma. Available at https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-tafasitamab-cxix-diffuse-large-b-cell-lymphoma. Accessed August 12, 2020.

2. Monjuvi (tafasitamab-cxix) for injection, for intravenous use. Morphosys US Inc, July 2020. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761163s000lbl.pdf. Accessed August 12, 2020.