Mosunetuzumab and Polatuzumab Vedotin as First-line Treatment for Large B Cell Lymphoma in Older Unfit or Frail Patients.

Authors

Adam J Olszewski, Herbert A Eradat, Abraham Avigdor, Netanel A Horowitz, Matthew S McKinney, Seung Tae Lee, Juan Miguel Bergua Burgues, Antonia Rodriguez Izquierdo, Mariana Bastos-Oreiro, Chezi Ganzel, Tae Min Kim, Youngwoo Jeon, Michał Taszner, Mayur S Narkhede, Won Seog Kim, Ho-Jin Shin, Dariusz Woszczyk, Neta Goldschmidt, Avrita Singh, Michael C Wei, Jue Wang, Connie Lee Batlevi, Wahib Ead, Martin Janousek, Gila Sellam, Wojciech Jurczak

Published in

Blood. Oct 05, 2026. Epub Oct 05, 2026.

Abstract

Older or medically unfit patients with diffuse large B-cell lymphoma (DLBCL) frequently cannot tolerate standard anthracycline-based immunochemotherapy, creating a persistent unmet clinical need. We conducted a multicenter, international, open-label phase I/II trial evaluating an immunotherapy-based first-line approach using subcutaneous mosunetuzumab in combination with polatuzumab vedotin in previously untreated patients classified as unfit or frail by simplified geriatric assessment (sGA). Participants received six cycles of polatuzumab vedotin with step-up-dosing of subcutaneous mosunetuzumab, followed by mosunetuzumab monotherapy for a planned total of eight cycles. The primary endpoint was objective response rate (ORR) at end of treatment, assessed by independent review using PET-CT Lugano 2014 criteria. Among participants treated at full dose (n=101), the median age was 81 years with 58% classified as unfit and 41% as frail by sGA. The ORR at the end of treatment was 61.4% (95% CI, 51.1-70.9), with a complete response (CR) rate of 56.4%. The best observed ORR and CR rates on therapy were 80.2% and 66.3%, respectively. With a median follow-up of 36.5 months, median investigator-assessed duration of response and overall survival were not reached; estimated 2-year progression-free and overall survival were 52.2% and 62.4%, respectively. Cytokine release syndrome occurred in 30.6% of participants and was predominantly grade 1. Infection-related mortality was observed, largely during the COVID-19 pandemic and among participants classified as frail. This geriatric assessment-guided treatment demonstrated durable efficacy and may represent a potential first-line treatment option for carefully selected unfit or frail patients with newly diagnosed DLBCL. Trial registration: #NCT03677154.

PMID:
42832423
Bibliographic data and abstract were imported from PubMed on 06 Oct 2026.

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