frontMIND phase III: Tafasitamab + lenalidomide + R-CHOP in DLBCL and HGBL

Results from the global, randomized, double-blind, phase III frontMIND trial (NCT04824092), investigating tafasitamab + lenalidomide (Tafa-Len) added to rituximab + cyclophosphamide + doxorubicin + vincristine + prednisone (R-CHOP) vs R-CHOP alone in 899 patients aged 18–80 years with previously untreated high-intermediate-risk or high-risk diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL), were published in The Lancet by Lenz et al. The primary endpoint was investigator-assessed progression-free survival (PFS). Key secondary endpoints included investigator-assessed event-free survival (EFS) and overall survival (OS).

Key data: At a median follow-up of 35.2 months, Tafa-Len-R-CHOP significantly reduced the risk of disease progression or death vs R-CHOP (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.59–0.96; p = 0.0194), with 2-year progression-free survival (PFS) rates of 71.1% vs 62.9%. In a predefined subgroup analysis, HRs for PFS were 0.59 (95% CI, 0.36–0.95) in the activated B-cell (ABC)-like cell-of-origin subtype and 0.69 (95% CI, 0.40–1.19) in the germinal centre B-cell (GCB)-like subtypes. EFS was also significantly improved with Tafa-Len-R-CHOP vs R-CHOP (HR, 0.79; 95% CI, 0.64–0.97; p = 0.0260), while median OS was not reached (NR) in either arm (HR, 0.85; 95% CI, 0.63–1.14; p = 0.2703). Grade ≥3 treatment-emergent adverse events (TEAEs) were more frequent with Tafa-Len-R-CHOP (87% vs 76%); the most common Grade ≥3 TEAEs were neutropenia (69% vs 58%), thrombocytopenia (27% vs 14%), anemia (24% vs 16%), and febrile neutropenia (16% vs 13%). Fatal TEAEs occurred in 6% vs 4% of patients; however, the overall number of deaths in the study was lower with Tafa-Len-R-CHOP vs R-CHOP (19% vs 22%).

Key learning: Tafa-Len-R-CHOP significantly improved PFS and EFS vs R-CHOP in previously untreated high-risk DLBCL or HGBL, with PFS advantages observed in several subgroups analysed, representing a potential new first-line treatment option for these patient populations. As expected from the addition of Tafa-Len to R-CHOP, rates of TEAEs were increased, but this did not impair R-CHOP dosing or scheduling.