Mosunetuzumab With Response-Adapted Polatuzumab Vedotin and Obinutuzumab in Untreated Indolent B-Cell Non-Hodgkin Lymphoma
Ryan C. Lynch, Christina Poh, Mazyar Shadman, Brian G. Till, Mengyang Di, Chaitra S. Ujjani, Vikram Raghunathan, Stephen D. Smith, David Maloney, Daria Gausman, Heather Rasmussen, David A. Russler-Germain, Todd A. Fehniger, David M. Kurtz, Ash Alizadeh, Jenna Voutsinas, Ajay K. GopalPURPOSE
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.