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

Author(s): Ryan C. Lynch, MD^1,2; Christina Poh, MD^1,2,3; Mazyar Shadman, MD^1,2; Brian G. Till, MD^1,2; Mengyang Di, MD, PhD^1,2; Chaitra S. Ujjani, MD^1,2; Vikram Raghunathan, MD^1,2; Stephen D. Smith, MD^1,2; David Maloney, MD, PhD^1,2; Daria Gausman, BS^1,2; Heather Rasmussen, BS^1,2; David A. Russler-Germain, MD, PhD⁴; Todd A. Fehniger, MD, PhD⁴; David M. Kurtz, MD, PhD^5,6; Ash Alizadeh, MD, PhD⁵; Jenna Voutsinas, MPH²; Ajay K. Gopal, MD^1,2;

Source: DOI: 10.1200/JCO-25-02906

Dr. Anjan Patel's Thoughts

This is a really encouraging look at chemo-free frontline therapy for symptomatic or high-burden FL and MZL. Eight cycles of mosunetuzumab alone produced a 71% complete response (CR) rate, escalation to pola-obinutuzumab for PET-positive patients pushed CR to 86%, and 2-year progression-free survival (PFS) was 89% with no maintenance. Toxicity was impressively outpatient-friendly: CRS was all grade 1, no one needed tocilizumab, and there was no immune effector cell–associated neurotoxicity syndrome (ICANS), though the shingles and HSV reactivations make a good case for antiviral prophylaxis. It's a small single-center study with two CD20-negative relapses to keep in mind, but the ctDNA–PET concordance hints at an MRD-guided "treat less when you can" future.

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.

Author Affiliations

¹University of Washington, Seattle, WA; ²Fred Hutchinson Cancer Center, Seattle, WA; ³City of Hope, Duarte, CA; ⁴Washington University School of Medicine, Saint Louis, MO; ⁵Stanford University School of Medicine, Stanford, CA; ⁶Foresight Diagnostics, Boulder, CO

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