Mosunetuzumab plus Pola-CHP compared with Pola-R-CHP in previously untreated DLBCL: final results from a phase 2 study

This phase 2 study evaluated mosunetuzumab plus cyclophosphamide, doxorubicin, prednisone, and polatuzumab vedotin (Pola-M-CHP) vs Pola-rituximab (R)-CHP for first-line treatment of diffuse large B-cell lymphoma. Patients were randomized 2:1 to receive 6 cycles of Pola-M-CHP or Pola-R-CHP on day 1 of each 21-day cycle. Mosunetuzumab was administered intravenously via step-up dosing during cycle 1 and at 30 mg on day 1 of subsequent cycles. The primary end point was independent review committee-assessed complete response (CR) rate by positron emission tomography-computed tomography. Overall, 62 patients were enrolled and received Pola-M-CHP (n = 40) or Pola-R-CHP (n = 22). CR rates were similar in both arms (72.5% with Pola-M-CHP vs 77.3% with Pola-R-CHP); the 24-month investigator-assessed progression-free survival rate was 70.8% (95% confidence interval [CI], 55.6-86.1) with Pola-M-CHP vs 81.8% (95% CI, 65.7-97.9) with Pola-R-CHP. The most common adverse event (AE) was cytokine release syndrome (68.4%; mostly grade 1 [52.6%], and primarily confined to cycle 1) with Pola-M-CHP and neutropenia/neutrophil count decreased (54.5%) with Pola-R-CHP. Neutropenia/neutrophil count decreased was the most frequently observed grade ≥3 AE in both arms (Pola-M-CHP, 36.8%; Pola-R-CHP, 22.7%). Rates of grade ≥3 AEs (86.8% vs 59.1%), serious AEs (63.2% vs 13.6%), and AEs leading to treatment discontinuation (13.2% vs 0%) were higher with Pola-M-CHP than Pola-R-CHP, respectively. Pharmacodynamic changes were supportive of mosunetuzumab's mechanism of action and its addition to the Pola-CHP combination. Pola-M-CHP, although an active combination, did not demonstrate a clinical benefit over Pola-R-CHP in this small study. This trial was registered at www.clinicaltrials.gov as #NCT03677141.

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Journal
Blood Advances
Published
2025-02-05
DOI
https://doi.org/10.1182/bloodadvances.2024014907
Citations
10
Primary Topic
Lymphoma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
14.72

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article

Mosunetuzumab plus Pola-CHP compared with Pola-R-CHP in previously untreated DLBCL: final results from a phase 2 study

Marc Hoffmann, Enkhtsetseg Purev, Jason R. Westin, Amitkumar Mehta et al.
10 citations
Blood Advances
Lymphoma Diagnosis and Treatment
14.72
article

Mosunetuzumab plus Pola-CHP compared with Pola-R-CHP in previously untreated DLBCL: final results from a phase 2 study

Marc Hoffmann, Enkhtsetseg Purev, Jason R. Westin, Amitkumar Mehta, Catherine Thiéblemont, Mariana Bastos‐Oreiro, Richard Greil, Sebastian Giebel, Reinhard Bucher, Eva M. González-Barca, Tycel Phillips, Michael C. Wei, Juan Bergua, Donald L. Yee, Jason Sit, Elicia Penuel, Jue Wang
article en
10 citations

Abstract

This phase 2 study evaluated mosunetuzumab plus cyclophosphamide, doxorubicin, prednisone, and polatuzumab vedotin (Pola-M-CHP) vs Pola-rituximab (R)-CHP for first-line treatment of diffuse large B-cell lymphoma. Patients were randomized 2:1 to receive 6 cycles of Pola-M-CHP or Pola-R-CHP on day 1 of each 21-day cycle. Mosunetuzumab was administered intravenously via step-up dosing during cycle 1 and at 30 mg on day 1 of subsequent cycles. The primary end point was independent review committee-assessed complete response (CR) rate by positron emission tomography-computed tomography. Overall, 62 patients were enrolled and received Pola-M-CHP (n = 40) or Pola-R-CHP (n = 22). CR rates were similar in both arms (72.5% with Pola-M-CHP vs 77.3% with Pola-R-CHP); the 24-month investigator-assessed progression-free survival rate was 70.8% (95% confidence interval [CI], 55.6-86.1) with Pola-M-CHP vs 81.8% (95% CI, 65.7-97.9) with Pola-R-CHP. The most common adverse event (AE) was cytokine release syndrome (68.4%; mostly grade 1 [52.6%], and primarily confined to cycle 1) with Pola-M-CHP and neutropenia/neutrophil count decreased (54.5%) with Pola-R-CHP. Neutropenia/neutrophil count decreased was the most frequently observed grade ≥3 AE in both arms (Pola-M-CHP, 36.8%; Pola-R-CHP, 22.7%). Rates of grade ≥3 AEs (86.8% vs 59.1%), serious AEs (63.2% vs 13.6%), and AEs leading to treatment discontinuation (13.2% vs 0%) were higher with Pola-M-CHP than Pola-R-CHP, respectively. Pharmacodynamic changes were supportive of mosunetuzumab's mechanism of action and its addition to the Pola-CHP combination. Pola-M-CHP, although an active combination, did not demonstrate a clinical benefit over Pola-R-CHP in this small study. This trial was registered at www.clinicaltrials.gov as #NCT03677141.

Blood AdvancesVol. 9(10)
Roche (Switzerland) (CH), Amgen (United States) (US), The University of Texas MD Anderson Cancer Center (US), Inserm (FR), Université Paris Cité (FR), University of Michigan (US), Paracelsus Medical University (AT), Hospital General Universitario Gregorio Marañón (ES), University of Alabama at Birmingham (US), Institut d'Investigació Biomédica de Bellvitge (ES), Sorbonne Paris Cité (FR), The University of Kansas Cancer Center (US), Institut Català d'Oncologia (ES), Hospital San Pedro de Alcántara (ES), Michigan Medicine (US), National Institute of Oncology (HU), University of Kansas Medical Center (US), Hôpital Saint-Louis (FR), Cellular Therapeutics (United Kingdom) (GB), The Maria Sklodowska-Curie National Research Institute of Oncology (PL)
Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, Sanofi, Gilead Sciences, Celgene, F. Hoffmann-La Roche, TG Therapeutics, BeiGene, Incyte, Seagen, Fundación para la Formación y la Investigación de los Profesionales de la Salud de Extremadura, Sociedad Española de Hematología y Hemoterapia, Servier, Swedish Orphan Biovitrum, MorphoSys, Genentech, Pharmacyclics, Daiichi Sankyo Europe
Good health and well-being
Openalex Percentile: Top 1%
Lymphoma Diagnosis and Treatment
14.72
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