Clinical benefit of tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma: real-world data from the EarlyMIND study

Abstract

Tafasitamab combined with lenalidomide was approved in Europe in 2021 for transplant-ineligible patients with relapsed/ refractory diffuse large B-cell lymphoma. Approval was based on the L-MIND study, which demonstrated a 57.5% overall response rate (ORR), 41.3% complete response (CR) rate, 12.1-month median progression-free survival (PFS), and 33.5-month median overall survival (OS) at 5 years. The multicenter retrospective EarlyMIND study analyzed real-world efficacy and treatment patterns of patients receiving tafasitamab plus lenalidomide for second-line (2L cohort) to fourth-line (3L + 4L cohort) treatment in the French Early Access Program. Outcomes were analyzed overall and according to number of previous lines of treatment. Post hoc analyses were conducted on subgroups based on prognostic factors, performance status, primary refractoriness, cell of origin, and treatment response. Overall, 186 patients were included (2L: N=105; 3L + 4L: N=81). The median age of the patients was 78 years; most patients had early relapsed disease (71.2%), including 60.2% with primary refractory disease. At a median follow-up of 8.2 months, best ORR was 46.8%, with a CR rate of 29%. The ORR was higher in the 2L cohort (50.5%) than in the 3L + 4L cohort (42%). The median PFS and OS were 4.7 and 10 months, respectively, in the overall population, 5.4 and 10.6 months in the 2L cohort, and 3.6 and 8.2 months in the 3L + 4L cohort. Long-lasting responses were observed in patients achieving CR, with median duration of response, PFS, and OS not reached. The median time to CR as best objective response was four cycles, regardless of treatment line. Despite involving a frail population with high-risk disease characteristics, results of this large real-world European retrospective study on tafasitamab plus lenalidomide are encouraging, with almost one third of patients experiencing long-lasting CR.

Figure 1.

Flowchart of the patients’ disposition in the EarlyMIND study. Disposition of enrolled patients. Eligible patients required enrollment in the tafasitamab French Expanded Access Program between January 27, 2022, and March 31, 2023. The full analysis set included patients who agreed to participate and received tafasitamab plus lenalidomide as second-, third-, or fourth-line therapy. The per-protocol set included those patients in the full analysis set who fulfilled all inclusion/exclusion criteria and had at least one evaluation of efficacy, with a minimum follow-up of 6 months. *Six without imaging, two with stable disease. 2L: second line; 3L: third line; 4L, fourth line; FAS: full analysis set; PP: per protocol.

Figure 2.

Best objective response for the per protocol population (N=186) and the subsets of patients treated in second line (N=105) and third + fourth line (N=81). PP: per protocol; 2L: patients treated in second line; 3L + 4L: patients treated in the third + fourth line; CR: complete response; PR: partial response.

Figure 3.

Overall survival and progression-free survival in the overall population, and in the subsets of patients treated in second line and third + fourth line. (A, B) Kaplan-Meier curves illustrating overall survival (A) and progression-free survival (B) for the per protocol population (N=186) and 2L and 3L+4L cohorts. Tick marks indicate censored patients. Log-rank P values are for the comparison of the 2L cohort versus the 3L+4L cohort. OS: overall survival; 95% CI: 95% confidence interval; 2L: patients treated in second line; 3L+4L: patients treated in third + fourth line; PFS: progression-free survival.

Figure 4.

Duration of response in the per protocol population and subpopulations with complete or partial responses. Kaplan-Meier curves illustrating the duration of response for the per protocol population (N=186) and the subsets of patients with a complete response (N=54) or a partial response (N=33). Tick marks indicate censored patients. Log-rank P values are for the comparison of patients with complete response versus those with a partial response. DOR: duration of response; 95% CI: confidence interval; CR: complete response; PR: partial response; NE: not evaluable; NR: not reached.

Figure 5.

Overall survival and progression-free survival in the subpopulations with complete or partial responses. (A, B) Kaplan-Meier curves illustrating overall survival (A) and progression-free survival (B) for the per protocol population (N=186) and the subsets of patients with a complete response (N=54) or a partial response (N=33). Tick marks indicate censored patients. Logrank P values are for the comparison of patients with complete response versus those with a partial response. OS: overall survival; CR: complete response; PR: partial response; 95% CI: confidence interval; NR: not reached; NE: not evaluable; PFS: progression-free survival.