---
title: "Mosunetuzumab Followed by Response-Adapted Polatuzumab Vedotin and Obinutuzumab in Untreated Indol"
id: "pubmed-42600120"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42600120"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42600120/"
doi: "10.1200/JCO-25-02906"
published_at: "2026-09-20T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Mosunetuzumab Followed by Response-Adapted Polatuzumab Vedotin and Obinutuzumab in Untreated Indol
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42600120
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42600120/)
- **DOI:** [10.1200/JCO-25-02906](https://doi.org/10.1200%2FJCO-25-02906)
- **Published At:** 2026-09-20T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This study tested a chemotherapy‑free strategy for untreated indolent B‑cell non‑Hodgkin lymphoma using initial **mosunetuzumab** followed by response‑adapted **polatuzumab vedotin** plus **obinutuzumab** for patients without PET‑CT complete response. - Eligible patients had follicular lymphoma (FL) or marginal zone lymphoma (MZL) requiring therapy and received eight cycles of mosunetuzumab as first‑line treatment. - Patients without a PET‑CT defined complete response (CR) after mosunetuzumab could receive six cycles of polatuzumab vedotin combined with obinutuzumab. - The primary endpoint was best overall response rate (ORR) and CR by FDG‑PET‑CT. - Forty‑two patients were enrolled (median age 60 years, range 36–83); most had advanced stage (93% stage III–IV) and 88% had FL; 31% had bulky disease (>7 cm). - End‑of‑treatment responses were high: ORR 100% and CR 86% across the cohort. - Response to mosunetuzumab alone was ORR 100% and CR 71%; patients not achieving CR could escalate to the polatuzumab/obinutuzumab regimen. - With median follow‑up of 34 months, 2‑year progression‑free survival (PFS) was 89% (95% CI, 80 to 100) and 2‑year overall survival was 100%. - Four progression events occurred: two with CD20 loss and two with histologic transformation. - **Cytokine release syndrome** occurred in 64% of patients (27/42), but all events were grade 1. Other safety details beyond CRS grading were not reported in the abstract. - The study supports a potentially effective chemotherapy‑sparing approach in untreated indolent B‑cell lymphoma, with durable PFS and an acceptable short‑term safety profile in this cohort.
## Clinical Analysis & Structured Key Points
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Epub 2026 Aug 14. # Mosunetuzumab With Response-Adapted Polatuzumab Vedotin and Obinutuzumab in Untreated Indolent B-Cell Non-Hodgkin Lymphoma [Ryan C Lynch](https://pubmed.ncbi.nlm.nih.gov/?term=Lynch+RC&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [Christina Poh](https://pubmed.ncbi.nlm.nih.gov/?term=Poh+C&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-3 "City of Hope, Duarte, CA."), [Mazyar Shadman](https://pubmed.ncbi.nlm.nih.gov/?term=Shadman+M&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [Brian G Till](https://pubmed.ncbi.nlm.nih.gov/?term=Till+BG&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [Mengyang Di](https://pubmed.ncbi.nlm.nih.gov/?term=Di+M&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [Chaitra S Ujjani](https://pubmed.ncbi.nlm.nih.gov/?term=Ujjani+CS&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [Vikram Raghunathan](https://pubmed.ncbi.nlm.nih.gov/?term=Raghunathan+V&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [Stephen D Smith](https://pubmed.ncbi.nlm.nih.gov/?term=Smith+SD&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [David Maloney](https://pubmed.ncbi.nlm.nih.gov/?term=Maloney+D&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [Daria Gausman](https://pubmed.ncbi.nlm.nih.gov/?term=Gausman+D&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [Heather Rasmussen](https://pubmed.ncbi.nlm.nih.gov/?term=Rasmussen+H&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [David A Russler-Germain](https://pubmed.ncbi.nlm.nih.gov/?term=Russler-Germain+DA&cauthor_id=42600120)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-4 "Washington University School of Medicine, Saint Louis, MO."), [Todd A Fehniger](https://pubmed.ncbi.nlm.nih.gov/?term=Fehniger+TA&cauthor_id=42600120)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-4 "Washington University School of Medicine, Saint Louis, MO."), [David M Kurtz](https://pubmed.ncbi.nlm.nih.gov/?term=Kurtz+DM&cauthor_id=42600120)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-5 "Stanford University School of Medicine, Stanford, CA.")[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-6 "Foresight Diagnostics, Boulder, CO."), [Ash Alizadeh](https://pubmed.ncbi.nlm.nih.gov/?term=Alizadeh+A&cauthor_id=42600120)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-5 "Stanford University School of Medicine, Stanford, CA."), [Jenna Voutsinas](https://pubmed.ncbi.nlm.nih.gov/?term=Voutsinas+J&cauthor_id=42600120)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [Ajay K Gopal](https://pubmed.ncbi.nlm.nih.gov/?term=Gopal+AK&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#full-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA.") Affiliations Expand ### Affiliations * 1 University of Washington, Seattle, WA. * 2 Fred Hutchinson Cancer Center, Seattle, WA. * 3 City of Hope, Duarte, CA. * 4 Washington University School of Medicine, Saint Louis, MO. * 5 Stanford University School of Medicine, Stanford, CA. * 6 Foresight Diagnostics, Boulder, CO. * PMID: **42600120** * DOI: [ 10.1200/JCO-25-02906 ](https://doi.org/10.1200/jco-25-02906) Item in Clipboard # Mosunetuzumab With Response-Adapted Polatuzumab Vedotin and Obinutuzumab in Untreated Indolent B-Cell Non-Hodgkin Lymphoma Ryan C Lynch et al. J Clin Oncol. 2026. Show details Display options Display options Format Abstract PubMed PMID J Clin Oncol Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22J+Clin+Oncol%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22J+Clin+Oncol%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42600120/) . 2026 Sep 20;44(27):2625-2633. doi: 10.1200/JCO-25-02906. Epub 2026 Aug 14. ### Authors [Ryan C Lynch](https://pubmed.ncbi.nlm.nih.gov/?term=Lynch+RC&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [Christina Poh](https://pubmed.ncbi.nlm.nih.gov/?term=Poh+C&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-3 "City of Hope, Duarte, CA."), [Mazyar Shadman](https://pubmed.ncbi.nlm.nih.gov/?term=Shadman+M&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [Brian G Till](https://pubmed.ncbi.nlm.nih.gov/?term=Till+BG&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [Mengyang Di](https://pubmed.ncbi.nlm.nih.gov/?term=Di+M&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [Chaitra S Ujjani](https://pubmed.ncbi.nlm.nih.gov/?term=Ujjani+CS&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [Vikram Raghunathan](https://pubmed.ncbi.nlm.nih.gov/?term=Raghunathan+V&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [Stephen D Smith](https://pubmed.ncbi.nlm.nih.gov/?term=Smith+SD&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [David Maloney](https://pubmed.ncbi.nlm.nih.gov/?term=Maloney+D&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [Daria Gausman](https://pubmed.ncbi.nlm.nih.gov/?term=Gausman+D&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [Heather Rasmussen](https://pubmed.ncbi.nlm.nih.gov/?term=Rasmussen+H&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [David A Russler-Germain](https://pubmed.ncbi.nlm.nih.gov/?term=Russler-Germain+DA&cauthor_id=42600120)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-4 "Washington University School of Medicine, Saint Louis, MO."), [Todd A Fehniger](https://pubmed.ncbi.nlm.nih.gov/?term=Fehniger+TA&cauthor_id=42600120)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-4 "Washington University School of Medicine, Saint Louis, MO."), [David M Kurtz](https://pubmed.ncbi.nlm.nih.gov/?term=Kurtz+DM&cauthor_id=42600120)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-5 "Stanford University School of Medicine, Stanford, CA.")[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-6 "Foresight Diagnostics, Boulder, CO."), [Ash Alizadeh](https://pubmed.ncbi.nlm.nih.gov/?term=Alizadeh+A&cauthor_id=42600120)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-5 "Stanford University School of Medicine, Stanford, CA."), [Jenna Voutsinas](https://pubmed.ncbi.nlm.nih.gov/?term=Voutsinas+J&cauthor_id=42600120)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA."), [Ajay K Gopal](https://pubmed.ncbi.nlm.nih.gov/?term=Gopal+AK&cauthor_id=42600120)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-1 "University of Washington, Seattle, WA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42600120/#short-view-affiliation-2 "Fred Hutchinson Cancer Center, Seattle, WA.") ### Affiliations * 1 University of Washington, Seattle, WA. * 2 Fred Hutchinson Cancer Center, Seattle, WA. * 3 City of Hope, Duarte, CA. * 4 Washington University School of Medicine, Saint Louis, MO. * 5 Stanford University School of Medicine, Stanford, CA. * 6 Foresight Diagnostics, Boulder, CO. * PMID: **42600120** * DOI: [ 10.1200/JCO-25-02906 ](https://doi.org/10.1200/jco-25-02906) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract **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.
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