Mosunetuzumab With Response-Adapted Polatuzumab Vedotin and Obinutuzumab in Untreated Indolent B-Cell Non-Hodgkin Lymphoma

PURPOSE: Chemoimmunotherapy has been the standard approach for untreated indolent B-cell lymphoma. We hypothesized that initial use of the CD3/CD20 bispecific mosunetuzumab followed by response-adapted polatuzumab vedotin and obinutuzumab would yield an optimized chemotherapy-free approach. METHODS: Previously untreated patients with follicular lymphoma (FL) and marginal zone lymphoma (MZL) with indication for treatment received eight cycles of mosunetuzumab. Those not achieving a complete response (CR) by positron emission tomography-computed tomography (PET-CT) following mosunetuzumab could go on to receive six cycles of polatuzumab vedotin and obinutuzumab. The primary end point was best overall response rate (ORR) of CR by fluorodeoxyglucose-PET-CT. RESULTS: The 42 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 (PFS) was 89% (95% CI, 80 to 100) and the 2-year overall survival was 100%. The four progression events included CD20 loss (2) and histologic transformation (2). Cytokine release syndrome occurred in 27 patients (64%), but all were grade 1. No patients required tocilizumab. CONCLUSION: Single-agent mosunetuzumab as well as response-adapted polatuzumab vedotin and obinutuzumab yield encouraging CR rates and PFS with limited toxicity among previously untreated patients with FL and MZL. This chemotherapy-free strategy may provide a template for larger study designs for personalized approaches in this population that balances efficacy with safety.