Multicenter phase 2 trial of atezolizumab, venetoclax, and obinutuzumab for Richter transformation diffuse large B-cell lymphoma

The diffuse large B-cell lymphoma variant of Richter transformation (DLBCL-RT) is typically chemoresistant and associated with a poor prognosis. The phase 2 MOLTO trial, at 15 centers in Italy and Switzerland, evaluated the chemotherapy-free combination of atezolizumab plus venetoclax and obinutuzumab as first-line treatment for DLBCL-RT. Patients received 35 three-week cycles of the combination. ORR at the end of cycle six (primary endpoint) was 67.9% (95% CI 47.6-84.1), reaching the primary endpoint. Treatment-emergent adverse events that were grade 3 or worse were reported in 61% of patients, and serious TRAEs in 29%. Two patients (7%) died during the trial of causes not considered as directly treatment-related. Immune-related adverse events were reported in 24.4%, none of which led to discontinuation. No tumor lysis syndrome was observed. The authors conclude that the combination of atezolizumab, venetoclax, and obinutuzumab was effective and safe as first-line treatment for DLBCL-RT.