The European Medicines Agency’s Committee for Medicinal Products for Human Use has issued a positive opinion in favor of granting conditional marketing authorization to the combination of tafasitamab-cxix and lenalidomide, followed by single-agent tafasitamab, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma who are not candidates for autologous stem cell transplant.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion in favor of granting conditional marketing authorization to the combination of tafasitamab-cxix (Monjuvi) and lenalidomide (Revlimid), followed by single-agent tafasitamab, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not candidates for autologous stem cell transplant (ASCT).1
The recommendation is supported by data from the phase 2 L-MIND study (NCT02399085), in which the doublet elicited an objective response rate (ORR) of 57.5% (n = 46/80; 95% CI, 45.9%-68.5%) at a least 35 months of follow-up.2 Of those who responded to treatment, 40.0% achieved a complete response and 17.5% experienced a partial response.
In patients who received 1 prior treatment (n = 40), the ORR with the combination was 67.5% (95% CI, 50.9%-81.4%), and in those who received 2 or more prior treatments (n = 40), the ORR was 47.5% (95% CI, 31.5%-63.9%).
“The CHMP’s positive opinion of tafasitamab is a pivotal step toward addressing an urgent unmet medical need for the 30% to 40% of patients with relapsed or refractory DLBCL who do not respond to initial therapy or relapse thereafter,” Steven Stein, MD, chief medical officer at Incyte, stated in a press release. “Following the US FDA’s approval of tafasitamib in July 2020, we eagerly await the European Commission’s decision as we look forward to bringing this new therapy to eligible patients in Europe as soon as possible.”
For the open-label, single-arm, phase 2 trial, investigators examined tafasitamab plus lenalidomide in 81 patients with relapsed/refractory DLBCL who are not eligible for ASCT. Patients needed to be aged 18 years or older, have previously received 1 to 3 regimens and have an ECOG performance status of 0 to 2. Patients who were primary refractory were excluded.
For cycles 1 to 3, participants received tafasitamab at a dose of 12 mg/kg on days 1, 8, 15, and 22. In cycles 4 through 12, tafasitamab was given at the same dose but just on days 1, 15, and 22. Lenalidomide was administered at a daily dose of 25 mg from days 1 to 21. If patients achieved disease stability or better, they went on to receive tafasitamab monotherapy at a dose of 12 mg/kg on days 1 and 15. These patients received treatment until disease progression.
The primary end point of the trial was ORR per independent review committee assessment and 2007 International Working Group response criteria, and secondary end points included progression-free survival (PFS), duration of response (DOR), overall survival (OS), and safety.
Of the 81 patients enrolled to the trial, 80 received 1 or more doses of both agents and they were included in the full analysis set for efficacy. All 81 patients were included in the safety analysis. Thirty-four patients received single-agent tafasitamab following lenalidomide discontinuation; 19 patients were still received the agent at a data cutoff of October 30, 2020.
The median age of study participants at the time of enrollment was 72 years (range, 41-86) and patients had received a median of 2 prior lines of therapy (range, 1-4) prior to study entry. Of the 80 patients included in the efficacy data set, 40 had received 1 prior treatment and 40 had received 2 or more prior treatments prior to trial enrollment.
Additional updated long-term data presented during the 2021 ASCO Annual Meeting showed that the median DOR with the doublet in the overall population was 43.9 months (95% CI, 26.1–not reached [NR]). In the subsets of patients who previously received 1 prior line or 2 or more prior lines of treatment, the median DOR was 43.9 months (95% CI, 9.1–NR) and NR (95% CI).
Moreover, the median PFS with the combination among all patients was 11.6 months (95% CI, 6.3-45.7); it was 23.5 months (95% CI, 7.4–NR) among those who received 1 prior treatment and 7.6 months (95% CI, 2.7–NR) among those who previously received 2 or more treatments.
The median OS in the overall population, the subset that received 1 prior therapy, and the subset that received 2 or more prior therapies was 33.5 months (95% CI, 18.3–NR), 45.7 months (95% CI, 24.6–NR), and 15.5 months (95% CI, 8.6–NR), respectively.
Regarding safety, tafasitamab plus lenalidomide was found to be well tolerated in the long-term follow-up analysis of the study. No unexpected adverse effects were reported, and no new safety signals were observed.
The most frequent treatment-emergent AEs that were grades 3 to 5 included neutropenia (49.4%), thrombocytopenia (17.3%), and febrile neutropenia (12.3%).
In July 2020, the FDA gave the green light to tafasitamab for use in combination with lenalidomide in adult patients with relapsed/refractory DLBCL not otherwise specified, including DLBCL arising from low-grade lymphoma, and who are not candidates for ASCT based on earlier data from L-MIND.3