On July 31, the U.S. Food and Drug Administration (FDA) approved tafasitamab-cxix (Monjuvi) 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.
Tafasitamab-cxix, a humanized Fc-modified cytolytic CD19-targeting monoclonal antibody, has been approved based on overall response rate in the phase II L-MIND study. Continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial. The FDA decision represents the first approval of a second-line treatment for adult patients with DLBCL progression during or after first-line therapy.
The FDA previously granted Fast Track and Breakthrough Therapy designations for the combination of tafasitamab-cxix and lenalidomide in relapsed or refractory DLBCL. The biologics license application for the drug was granted Priority Review and approved under the FDA’s Accelerated Approval program.
L-MIND is an open label, multicenter, single-arm trial of tafasitamab-cxix in combination with lenalidomide as a treatment for adult patients with relapsed or refractory DLBCL. Patients received tafasitamab-cxix at 12 mg/kg intravenously with lenalidomide (25 mg orally on days 1 to 21 of each 28-day cycle) for a maximum of 12 cycles, followed by tafasitamab-cxix as monotherapy. Results from the study showed an overall response rate of 55% (primary endpoint), including a complete response rate of 37% and a partial response rate of 18%. The median duration of response was 21.7 months (key secondary endpoint).
Efficacy was based on best overall response rate, defined as complete and partial responders and response duration, as assessed by an independent review committee. The best overall response rate in 71 patients with a diagnosis of DLBCL confirmed by central pathology was 55% (95% confidence interval = 43%–67%), with complete responses in 37% and partial responses in 18% of patients. Median response duration was 21.7 months (range = 0–24 months).
The most common adverse reactions (≥20%) were neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, respiratory tract infection, and decreased appetite.
The recommended tafasitamab-cxix dose is 12 mg/kg as an intravenous infusion.