The FDA has granted accelerated approval to tafasitamab-cxix (Monjuvi®, MorphoSys US Inc.) 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, who are ineligible for autologous stem cell transplantation.
The approval of tafasitamab, a CD19-directed cytolytic antibody, is based on efficacy data from the single-arm, international phase 2 L-MIND trial (NCT02399085), which enrolled adults with histologically confirmed DLBCL that had relapsed or was refractory following treatment with one to three systemic regimens, including at least one anti-CD20 therapy, who were ineligible for high-dose chemotherapy and subsequent autologous stem cell transplantation. Patients were co-administered intravenous tafasitamab 12 mg/kg and oral lenalidomide 25 mg/day for up to twelve 28-day cycles, followed by tafasitamab monotherapy in patients with stable disease or better, until disease progression. The trial's primary end point was objective response rate, including complete or partial responses.
Eighty patients received at least one dose of both tafasitamab and lenalidomide. With a median follow-up of 13.2 months, 60% of these patients experienced an objective response to tafasitamab/lenalidomide, including 43% complete responses and 18% partial responses. Serious adverse events occurred in 51% of 81 patients who received at least one dose of either study medication, with the most frequent being pneumonia (6%), febrile neutropenia (6%), pulmonary embolism (4%), bronchitis (2%), atrial fibrillation (2%), and congestive cardiac failure (2%). Frequent treatment-emergent adverse events of grade 3 or higher included neutropenia (48%), thrombocytopenia (17%), and febrile neutropenia (12%). Adverse reactions of any grade occurring in at least 20% of patients included neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, respiratory tract infection, and decreased appetite.
"Patients with relapsed or refractory diffuse large B-cell lymphoma who are ineligible for autologous stem cell transplantation have poor outcomes and few treatment options," commented the study investigators in their July publication in The Lancet Oncology, led by first author Gilles Salles, MD, Head of the Hematology Department of the Centre Hospitalier Lyon-Sud, Pierre-Bénite, France. "Tafasitamab in combination with lenalidomide was well tolerated and resulted in a high proportion of patients with relapsed or refractory diffuse large B-cell lymphoma ineligible for autologous stem cell transplantation having a complete response and might represent a new therapeutic option in this setting."
Since tafasitamab was granted accelerated approval, continued approval may be contingent upon verification and description of clinical benefit in one or more confirmatory trials.
For More Information
Salles G, Duell J, González Barca E, et al (2020). Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol, 21(7):978-988. DOI:10.1016/S1470-2045(20)30225-4
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