Mosunetuzumab (CD20xCD3 bispecific) + response-adapted polatuzumab vedotin (CD79b ADC) drives 86% PET-CR and 89% 2y PFS in untreated indolent NHL

Mosunetuzumab is an IV CD20xCD3 T-cell–engaging bispecific antibody; polatuzumab vedotin is a CD79b-directed antibody–drug conjugate, and obinutuzumab is a type II anti-CD20 mAb. In this single-arm, response-adapted frontline study in follicular lymphoma (FL) and marginal zone lymphoma (MZL) requiring therapy, patients received 8 cycles of mosunetuzumab, with PET-CT non-CRs eligible to add 6 cycles of polatuzumab vedotin + obinutuzumab (n=42; 88% FL; 93% stage III–IV; 31% bulky >7cm). End-of-treatment ORR/CR was 100%/86% (mosunetuzumab alone ORR/CR 100%/71%), and at median follow-up 34 months, 2-year PFS was 89% (95% CI, 80–100) with 2-year OS 100%. Cross-trial comparisons with established frontline regimens are difficult because GALLIUM and RELEVANCE report longer 3-year PFS landmarks; the more distinctive signal here is the 86% PET-CR rate and encouraging early disease control achieved with a chemotherapy-free, response-adapted strategy rather than evidence yet of superior PFS. Safety was driven by cytokine release syndrome (CRS) in 64%, all grade 1, with no tocilizumab use reported; only 4 progressions were seen, including CD20 loss (n=2) and histologic transformation (n=2).