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2025-04-03T09:22:00.000Z

Phase II study: Mosunetuzumab plus Pola-CHP vs Pola-R-CHP in DLBCL

Apr 3, 2025
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Learning objective: After reading this article, learners will be able to cite a new clinical development in diffuse large B-cell lymphoma.

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While the approval of Pola-R-CHP can improve PFS for patients with previously untreated DLBCL, a need remains for novel combination therapies to further improve outcomes for these patients. Replacing rituximab with the CD20xCD3 bispecific antibody mosunetuzumab may offer a combination with promising potential due to the distinct, non-overlapping mechanisms of action of Pola-CHP and mosunetuzumab.

A recent phase II trial (NCT03677141) compared the efficacy and safety of Pola-M-CHP vs Pola-R-CHP in patients with untreated DLBCL . Patients were randomly assigned in a 2:1 ratio to receive Pola-M-CHP (n = 40) or Pola-R-CHP (n = 22). The primary endpoint was the IRC-assessed CR rate by PET-CT. Key secondary endpoints included IRC-assessed CR rate at the PRA with CT, ORR, safety, and tolerability.    

Results were published by Westin et al. in Blood Advances.1


Key learnings
Patients in the Pola-M-CHP and Pola-R-CHP groups showed similar IRC-assessed CR rates (72.5% vs 77.3%) and ORR (75.0% vs 86.4%).
IRC-assessed CR rate (75.0% vs 68.2%) and ORR (80.0% vs 77.3%) at the PRA were also similar in the Pola-M-CHP and Pola-R-CHP groups, respectively.
The most common Grade ≥3 AE in both the Pola-M-CHP and Pola-R-CHP groups was neutropenia (63.2% vs 40.9%). Grade ≥3 AEs (86.8% vs 59.1%), SAEs (63.2% vs 13.6%), and AEs leading to treatment discontinuation (13.2% vs 0%) were higher in the Pola-M-CHP group than the Pola-R-CHP group.
Although Pola-M-CHP is an active combination, it did not show a clear efficacy advantage over Pola-R-CHP as a first-line treatment in patients with DLBCL. Future dose optimization studies may provide further insights.

Abbreviations: AE, adverse event; CR, complete response, CT, computer tomography; DLBCL, diffuse large B-cell lymphoma; IRC, independent review committee; ORR, overall response rate; PET-CT, positron emission tomography-computer tomography; PFS, progression-free survival; PRA, primary response assessment; Pola-M-CHP, polatuzumab vedotin, mosunetuzumab, cyclophosphamide, doxorubicin, and prednisone; Pola-R-CHP, polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone; SAE, serious adverse event.

  1. Westin JR, Phillips TJ, Mehta A, et al. Mosunetuzumab plus Pola-CHP compared with Pola-R-CHP in previously untreated DLBCL: Final results from a Phase II study. Blood Adv. 2025. Online ahead of print. DOI: 10.1182/bloodadvances.2024014907

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