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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.
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