Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma

Abstract

Tafasitamab (MOR208), an Fc-modified, humanized, anti-CD19 monoclonal antibody, combined with the immunomodulatory drug lenalidomide was clinically active with a good tolerability profile in the open-label, single-arm, phase II L-MIND study of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem-cell transplantation. To assess long-term outcomes, we report an updated analysis with ≥35 months' follow-up. Patients were aged >18 years, had received one to three prior systemic therapies (including ≥1 CD20-targeting regimen) and Eastern Cooperative Oncology Group performance status 0-2. Patients received 28-day cycles of tafasitamab (12 mg/kg intravenously), once weekly during cycles 1-3, then every 2 weeks during cycles 4-12. Lenalidomide (25 mg orally) was administered on days 1-21 of cycles 1-12. After cycle 12, progression-free patients received tafasitamab every 2 weeks until disease progression. The primary endpoint was best objective response rate. After ≥35 months' follow-up (data cut-off: October 30, 2020), the objective response rate was 57.5% (n=46/80), including a complete response in 40.0% of patients (n=32/80) and a partial response in 17.5% of patients (n=14/80). The median duration of response was 43.9 months (95% confidence interval [95% CI]: 26.1-not reached), the median overall survival was 33.5 months (95% CI: 18.3-not reached) and the median progression-free survival was 11.6 months (95% CI: 6.3-45.7). There were no unexpected toxicities. Subgroup analyses revealed consistent long-term efficacy results across most subgroups of patients. This extended follow-up of L-MIND confirms the long duration of response, meaningful overall survival, and well-defined safety profile of tafasitamab plus lenalidomide followed by tafasitamab monotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma ineligible for autologous stem cell transplantation. ClinicalTrials.gov identifier: NCT02399085.

Figures

Figure 1.

CONSORT (Consolidated Standards of Reporting Trials) diagram of the L-MIND study at the October 30, 2020 data cut-off.

Figure 2.

Proportion of patients in remission. (A-C) Kaplan-Meier plots of duration of response (A), progression-free survival. (B) and overall survival (C) after 35 months of follow-up. 95% CI. 95% confidence interval; CR: complete response; DoR: duration of response; NE: not evaluable; NR: not reached; OS: overall survival; PD: progressive disease; PFS: progression- free survival; PR: partial response; SD: stable disease.

Figure 3.

Kaplan-Meier estimates of 30-month time-toevent endpoints. (A) Duration of response,* (B) progression-free survival and (C) overall survival rates. *Based on patients who achieved an objective response (CR or PR) in the respective subgroups. 95% CI: 95% confidence interval; DoR: duration of response; IPI: International Prognostic Index; nC: number of patients censored; nE: number of patients with event; nR: number of patients at risk; n#: number of responders within each subgroup (A: DoR), or number of overall patients within each subcategory (B: PFS; C: OS); OS: overall survival; PFS: progression- free survival. The vertical line indicates the 30- month DoR (A), PFS (B) and OS (C) rates across all responders/patients.