The European Commission has granted a conditional marketing authorization to tafasitamab plus lenalidomide followed by single-agent tafasitamab for use in adult patients with relapsed/refractory diffuse large B-cell lymphoma who are not candidates for autologous stem cell transplant.
The European Commission has granted a conditional marketing authorization to tafasitamab (Minjuvi) plus lenalidomide (Revlimid) followed by single-agent tafasitamab for use in adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who are not candidates for autologous stem cell transplant (ASCT).1
The regulatory decision follows a positive opinion issued in June 2021 by the European Medicines Agency’s Committee for Medicinal Products for Human Use,2 which was supported by data from the phase 2 L-MIND study (NCT02399085).
Results demonstrated that the combination elicited an objective response rate (ORR) of 56.8% per independent review committee (IRC) assessment; this included a complete response (CR) rate of 39.5% and a partial response (PR) rate of 17.3%. Moreover, the median duration of response (DOR) achieved with the regimen was 43.9 months after a minimum follow-up of 35.0 months.
“The approval of [tafasitamab] is a crucial milestone for patients with relapsed or refractory DLBCL in Europe,” Jean-Paul Kress, MD, chief executive officer at MorphoSys, stated in a press release. “DLBCL is the most common type of non-Hodgkin lymphoma in adults and [tafasitamab] addresses an urgent unmet medical need for the 30% to 40% of people who do not respond to or relapse, after initial therapy.”
The single-arm, open-label, phase 2 trial enrolled patients with relapsed or refractory DLBCL who previously received at least 1, but no more than 3 lines of therapy, which included an CD20-targeting therapy like rituximab (Rituxan). To be eligible for enrollment, patients needed to be at least 18 years of age and have an ECOG performance status of 0 to 2.3 Patients could not be candidates for high-dose chemotherapy or ASCT, nor could they be primary refractory.
A total of 81 patients were enrolled to the trial. Participants received tafasitamab plus lenalidomide, followed by tafasitamab monotherapy. Intravenous tafasitamab was given at a dose of 12 mg/kg once weekly during cycles 1 to 3, with a loading dose on day 4 of cycle 1, then every 2 weeks during cycles 4 through 12. Oral lenalidomide was given at a dose of 25 mg on days 1 through 21 of cycles 1 to 12. After cycle 12, patients who were free of progression received tafasitamab at 12 mg/kg on days 1 and 15 of every 28-day cycle every 2 weeks until disease progression.
The primary end point of the trial was IRC-assessed ORR, based on the 2007 International Working Group response criteria. Key secondary end points comprised DOR, progression-free survival, overall survival (OS), and safety.
Data presented during the 2021 ASCO Annual Meeting showed that of the 81 patients enrolled, 80 received 1 or more doses of both tafasitamab and lenalidomide and were included in the full analysis set for efficacy. Thirty-four patients received single-agent tafasitamab following lenalidomide discontinuation. Of these patients, 15 stopped receiving tafasitamab at the data cutoff of the analysis, which left 19 patients still receiving therapy.
Study participants had a median age of 72 years (range, 41-86) at baseline and had previously received a median of 2 lines of therapy (range, 1-4) prior to study start. Of the 80 patients included in the analysis, half had received 1 prior treatment and the other half received 2 or more prior treatments.
At a median follow-up of 42.7 months, the median OS for the full efficacy population was 33.5 months (95% CI, 18.3–not reached [NR]). Patients who had a PR as their best response to treatment experienced a median OS of 22.5 months (95% CI, 8.6–NR). The median OS had not yet been reached in those who achieved a CR as their best response to the regimen (95% CI, 45.7–NR).
Overall, tafasitamab plus lenalidomide was well tolerated with no unexpected or new safety signals reported. The most common treatment-emergent adverse effects (TEAEs) that were grade 3 to 5 in severity included neutropenia (49.4%), thrombocytopenia (17.3%), and febrile neutropenia (12.3%).
The most common TEAE that resulted in tafasitamab/lenalidomide interruption was neutropenia. During the monotherapy phase of the trial, 52.5% of patients required an interruption of tafasitamab because of at least 1 TEAE, the most common of which were neutropenia (n = 9), leukopenia (n = 9), and respiratory tract infections (n = 6).
Warnings and precautions for tafasitamab include infusion-related reactions, myelosuppression, infections, and tumor lysis syndrome.
“The data from the L-MIND study demonstrate the potential benefits, including long duration of response, that tafasitamab may have for eligible [patients with] DLBCL,” Pier Luigi Zinzani, MD, PhD, professor and head of the Lymphoma Group at the University of Bologna, stated in the press release. “It is encouraging to see new treatments become available for these patients, especially given the historical lack of treatment options in this area.”
In July 2020, the FDA approved the combination of tafasitamab and lenalidomide in the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low-grade lymphoma, and who are not eligible for ASCT.4 The decision was based on findings from L-MIND.