Mosunetuzumab in R/R Richter’s transformation: Phase I/II study results

Results from a single-arm expansion cohort of the phase II, multicenter, open-label GO29781 study (NCT02500407), evaluating mosunetuzumab in 20 patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL)-type Richter’s transformation (RT) who had received ≥1 prior line of therapy, were published in Blood Advances by Lewis et al. The primary endpoints were safety and tolerability, and the key secondary endpoints included complete response (CR) rate, overall response rate (ORR), duration of response (DoR), duration of CR, progression-free survival (PFS), and overall survival (OS).

Key data: Adverse events (AEs) of any grade were reported in all patients, with 95% of patients experiencing an AE related to mosunetuzumab. Grade ≥3 AEs were reported in 80% of patients, with 45% experiencing Grade ≥3 AEs related to mosunetuzumab. Mosunetuzumab-related serious AEs (SAEs) were reported in 55% of patients. There were no Grade 5 AEs (excluding death from progressive disease) or AEs leading to treatment discontinuation. The most common any grade treatment-related AEs (TRAEs) were cytokine release syndrome (CRS; 65%), infection (35%), fatigue (25%), hypophosphatemia (25%), pyrexia (25%), abdominal pain (20%), elevated alanine aminotransferase (20%), and elevated aspartate aminotransferase (15%). The best ORR was 40%, with a CR in 20% of patients. The median PFS was 3.2 months, and the median OS was 10.2 months.

Key learning: Mosunetuzumab demonstrated a manageable safety profile and durable responses in R/R RT, supporting further investigation as monotherapy and in combination with novel agents or chemotherapy.