Mosunetuzumab with response-adapted polatuzumab vedotin and obinutuzumab in untreated indolent B-cell Hodgkin lymphoma

Chemoimmunotherapy has been the standard approach for untreated indolent B-cell lymphoma. A multicenter study in the US evaluated first-line mosunetuzumab (CD3/CD20 bispecific antibody) followed by response-adapted polatuzumab vedotin and obinutuzumab as chemotherapy-free approach for follicular lymphoma (FL) and marginal zone lymphoma (MZL). Patients received eight cycles if mosunetuzumab; those not achieving a complete response (CR) by PET-CT could go on to receive six cycles of polatuzumab vedotin and obinutuzumab. The primary endpoint was best overall response rate (ORR) of CR. Forty-two enrolled patients had a median age of 60 years (range 36-83), 39 were stage III to IV (93%), 37 (88%) had FL, and 13 (31%) had bulk > 7 cm. The end-of-treatment ORR and CR rates were 100% and 86%, respectively. The ORR and CR to mosunetuzumab alone were 100% and 71%, respectively. With a median follow-up of 34 months, the 2-year progression-free survival rate was 89% (95% CI 80-100) and the 2-year overall survival rate was 100%. The four progression events included CD20 loss (n=2) and histologic transformation (n=2). Cytokine release syndrome, all grade 1, occurred in 27 patients (64%). No patients required tocilizumab. The authors conclude that single-agent mosunetuzumab as well as response-adpated polatuzumab vedotin and obinutuzumab yielded encouraging CR rates and progression-free survival with limited toxicity among previously untreated patients with FL or MZL.