Safety and efficacy of tafasitamab ± lenalidomide added to first-line R‑CHOP for DLBCL: Phase 1b First-MIND study.

Anti-CD19 immunotherapy tafasitamab in combination with lenalidomide is used in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem cell transplant. Open-label, phase 1b, First-MIND study assessed safety and preliminary efficacy of tafasitamab + R-CHOP ± lenalidomide as first-line therapy in patients with DLBCL. Adults with newly-diagnosed, untreated DLBCL (ECOG PS 0-2, IPI 2-5), were randomly assigned to R-CHOP+tafasitamab (Arm T) or R-CHOP+tafasitamab+lenalidomide (Arm T/L) for six cycles. Primary endpoint was safety; secondary endpoints included overall response rate (ORR) and complete response (CR) rate at end of treatment (EoT). From Dec2019-Aug2020, 83 patients were screened, 66 treated (n=33 per arm). All patients had ≥1 treatment-emergent adverse event, mostly grade 1/2. Grade ≥3 neutropenia and thrombocytopenia occurred in 57.6% and 12.1% of patients (Arm T), and 84.8% and 36.4% (Arm T/L). Non-hematologic toxicities occurred at similar rates between arms. Mean relative dose intensity of R-CHOP was 89% or higher in both arms. ORR at EoT was 75.8% (CR 72.7%) in Arm T and 81.8% (CR 66.7%) in Arm T/L; best ORR across visits was 90.0% and 93.9%. Eighteen-month duration of response and duration of CR rates were 72.7% and 74.5% (Arm T), and 78.7% and 86.5% (Arm T/L); 24-month progression-free survival and overall survival rates were 72.7% and 90.3% (Arm T), and 76.8% and 93.8% (Arm T/L). Manageable safety and promising signals of efficacy were observed in both arms. Potential benefit of adding tafasitamab+lenalidomide to R-CHOP is being investigated in phase 3 frontMIND (NCT04824092).