Tafasitamab Plus R-CHOP With or Without Lenalidomide Yields Encouraging Efficacy, Manageable Safety Among Patients With Untreated DLBCL

Results from the Phase 1b First-MIND Study

A combination of tafasitamab plus the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen with or without the addition of lenalidomide demonstrated encouraging efficacy and manageable safety among patients with untreated diffuse large B-cell lymphoma (DLBCL), according to results of the phase 1b First-MIND study published in Blood. 

David Belada, MD, Charles University, Hospital and Faculty of Medicine, Hradec Králové, Czech Republic, and coauthors stated, “30% to 40% of patients experience relapsed or refractory (R/R) disease” after receiving first-line treatment of R-CHOP alone for DLBCL. The study authors noted that although other trials have attempted to improve disease outcomes among these patients by implementing supplementary agents, “all failed to improve overall survival (OS).” 

According to Dr Belada et al, there is “an unmet need remains to improve the current standard of care for patients with treatment-naïve DLBCL, particularly those with higher-risk disease.” This unmet need was the impetus of the phase 1b First-MIND study, which aimed to assess the preliminary efficacy and safety of anti-CD19 immunotherapy tafasitamab plus R-CHOP with or without lenalidomide among patients with untreated DLBCL. The primary end point was safety, and the secondary end points included the overall response rate (ORR) and complete response (CR) rate at the end of treatment. 

A total of 66 patients with untreated DLBCL and International Prognostic Index (IPI) scores of 2 to 5 were randomly assigned to receive either R-CHOP plus tafasitamab (n = 33) in arm T, or R-CHOP plus tafasitamab and lenalidomide (n = 33) in arm T/L, for 6 cycles. 

Regarding safety, results indicated that all patients had ≥1 treatment-emergent adverse event, the majority being grade 1 or 2. Adverse events of particular interest were grade ≥3 neutropenia, which occurred in 57.6% of patients in arm T and 84.8% in arm T/L, and grade ≥3 thrombocytopenia, which occurred in 12.1% of patients in arm T and 36.4% in arm T/L. Non-hematologic toxicities were comparable between arms. 

In arm T, the ORR at the end of treatment was 75.8%, and the CR at the end of treatment was 72.7%. In arm T/L, the ORR at the end of treatment was 81.8%, and the complete response at the end of treatment was 66.7%. The best ORR across visits was 90% and 93.9%. The 18-month duration of response and duration of CR rates were 72.7% and 74.5% in arm T, and 78.7% and 86.5% in arm T/L. The 24-month progression-free and overall survival rates were 72.7% and 90.3% in arm T, and 76.8% and 93.8% in arm T/L. 

Dr Belada et al concluded, “The phase 1b First-MIND study established the feasibility of adding tafasitamab ± lenalidomide to R-CHOP in the first-line setting in patients with IPI from 2 to 5 DLBCL, demonstrating a manageable safety profile.”

“Furthermore, preliminary efficacy suggests a potential clinical benefit for this regimen in patients who received no previous treatment, and biomarker data support potential future options for prognostic testing,” they added. 

Source: 

Belada D, Kopeckova K, Burgues JMB, et al. Safety and efficacy of tafasitamab with or without lenalidomide added to first-line R-CHOP for DLBCL: the phase 1b First-MIND study. Blood. Published online October 19, 2023. doi: 10.1182/blood.2023020637