New therapeutic options for relapsed/refractory diffuse large b-cell lymphoma. Treatment with tafasitamab + lenalidomide

Abstract

Patients with primary refractory or early-relapsed diffuse large B-cell lymphoma (DLBCL) constitute a subgroup of patients with a poor prognosis and limited results with conventional salvage immunochemotherapy. CD19 is a transmembrane glycoprotein expressed at various stages of B cell development, playing a crucial role in signaling for survival and proliferation of malignant B cells. Tafasitamab is a monoclonal antibody that, after binding to CD19, promotes B lymphocyte lysis through antibody-dependent cellular cytotoxicity and phagocytosis, as well as the direct induction of cell death by apoptosis. Its action is synergistic when combined with lenalidomide, which increases both antibody-dependent and NK cell-mediated cellular cytotoxicity.

The combination of tafasitamab and lenalidomide has been shown to be effective in the treatment of patients with relapsed/refractory DLBCL after one to three prior lines of systemic therapy who were not candidates for transplantation or who had rejected it. In the L-Mind study, tafasitamab was administered at a dose of 12 mg/kg on days 1, 8, 15 y 22 during the first three cycles (plus an additional dose on day 4 of the first cycle), and on days 1 and 15 during cycles 4 through 12. This monotherapy was continued until disease progression or unacceptable toxicity. Lenalidomide was administered at a dose of 25 mg/day for 21 days, in cycles every 28 days, for a maximum of 12 cycles. The L-Mind study included 81 patients, who, at extended 5-year follow-up, showed an objective response rate of 57.5%, with 41.3% complete response (CR) and 16.3% partial response (PR). With a median follow-up of 44 months, the median duration of response was not achieved, and the median progression-free survival (PFS) and overall survival (OS) were 11.6 and 33.5 months, respectively.  The most frequent adverse reactions were: infections (73%, with grades 3-4 in 28%), neutropenia (51%, grades 3-4 in 49%), asthenia (40%), anemia (36%, grades 3-4 in 7%), diarrhea (36%), thrombocytopenia (31%, grades 3-4 in 17%), cough (26%), peripheral edema (24%), pyrexia (24%), and decreased appetite (22%). The incidence of non-hematological adverse events during tafasitamab monotherapy (without lenalidomide) decreased by at least 10%, and the incidence of hematological adverse events decreased by at least 20%, with no episodes of febrile neutropenia during the tafasitamab monotherapy phase. The study concluded that the tafasitamab + lenalidomide combination was well tolerated, with a high proportion of patients with R/R DLBCL ineligible for autologous transplantation achieving complete remission (CR), making this regimen a new therapeutic option in this patient population.Based on the results of the L-MIND study, the combination received accelerated approval in the United States in July 2020, in Europe in August 2021, and in Argentina in 2025.   Practical recommendations for drug management and dose adjustments in response to adverse events are detailed. Based on these efficacy results, new combinations of tafasitamab are being explored, as well as its use in other earlier therapeutic lines.