Phase I/II GO40554 trial: First-line Mosun + Pola in older patients with DLBCL

Results from the multicenter, international, open-label, phase I/II GO40554 (NCT03677154) trial, evaluating subcutaneous mosunetuzumab (Mosun) + polatuzumab vedotin (Pola) as first-line treatment in older patients with diffuse large B-cell lymphoma (DLBCL) classified as unfit or frail by simplified geriatric assessment (sGA), were published in Blood by Olszewski et al. The primary efficacy endpoint was overall response rate (ORR) at the end of treatment (EoT).

Key data: The median age was 81 years (range, 66–94). In the efficacy analysis set (n = 101), the ORR at EoT was 61.4% (95% confidence interval [CI], 51.1–70.9), with a complete response (CR) rate of 56.4% (95% CI, 46.2–66.3). The best observed ORR and CR rates during treatment were 80.2% and 66.3%, respectively. At a median follow-up of 36.5 months, median progression-free survival (PFS) was 30.4 months and median overall survival (OS), duration of CR (DoCR), and duration of response (DoR) were not reached (NR). Estimated 2-year PFS, OS, DoCR, and DoR were 52.2%, 62.4%, 72.8%, and 61.1%, respectively. Grade ≥3 adverse events (AEs) were reported in 61.1% of patients, with serious AEs (SAEs) in 47.2% of patients. The most common AE was neutropenia (any grade, 36.1%; Grade ≥3, 30.6%). Cytokine release syndrome (CRS) was reported in 30.6% of patients (Grade 1, 23.1%; Grade 2, 5.6%; Grade 3, 1.9%). Infections were reported in 51.9% of patients, with Grade 5 infections in 12% of patients; infection-related mortality occurred predominantly during the peak of the COVID-19 pandemic and disproportionately affected participants classified as frail.

Key learning: In the GO40554 trial, Mosun + Pola demonstrated durable efficacy as first-line therapy in older, frail or unfit patients with DLBCL, supporting further prospective evaluation of immunotherapy-based, chemotherapy-sparing approaches in this population. While the safety profile was generally manageable, infections, including fatal infections, highlight the need for vigilance and appropriate prophylaxis.