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

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.

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Journal
Blood
Published
2026-10-05
DOI
https://doi.org/10.1182/blood.2026035116
Primary Topic
Lymphoma Diagnosis and Treatment
Type
article
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article

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

Martin Janousek, Mayur Subhash Narkhede, Abraham Avigdor, Netanel A. Horowitz et al.
Blood
Lymphoma Diagnosis and Treatment
article

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

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

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.

Blood
Roche (Switzerland) (CH), University of Maryland, Baltimore (US), University of California, Los Angeles (US), University of Opole (PL), Duke University (US), Genentech, Hebrew University of Jerusalem (IL), Brown University (US), Sheba Medical Center (IL), Hadassah Medical Center (IL), Rambam Health Care Campus (IL), Shaare Zedek Medical Center (IL), Samsung Medical Center (KR), Seoul National University Hospital (KR), Bikur Cholim Hospital (IL), Hospital General Universitario Gregorio Marañón (ES), Hospital Universitario 12 De Octubre (ES), The Catholic University of Korea Yeouido St. Mary's Hospital (KR), Hospital San Pedro de Alcántara (ES), Pusan National University Hospital (KR), Duke Medical Center (US), The Maria Sklodowska-Curie National Research Institute of Oncology (PL), Mercy Health (US), Gdańsk Medical University (PL)
Openalex Percentile: Top 12%
Lymphoma Diagnosis and Treatment
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