Favorable impact of zanubrutinib combined with R-CHOP regimen in MYD88-mutated new-diagnosed diffuse large B-cell lymphoma: a retrospective study with propensity score-matched analysis

TL;DR

Adding zanubrutinib to standard treatment may improve outcomes for patients with a specific mutation in a type of lymphoma.

Contribution

ZR-CHOP shows potential in MYD88-mutated DLBCL, particularly in patients with MYD88/CD79B double mutations.

Findings

ZR-CHOP group had a 75.0% complete response rate compared to 67.5% in the control group.

Patients with MYD88/CD79B double mutations had a 90.0% complete response rate.

ZR-CHOP showed similar progression-free and overall survival rates compared to standard treatment.

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, with MYD88 mutations associated with poor outcomes. Enhancing standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy with targeted agents such as zanubrutinib, a selective Bruton tyrosine kinase inhibitor, may improve patient prognosis. This retrospective study evaluated patients with MYD88-mutated DLBCL treated with zanubrutinib plus R-CHOP (ZR-CHOP). The ZR-CHOP group (n = 20) was compared with a propensity score-matched control group (n = 40) of patients without MYD88 mutation who received standard R-CHOP. Key outcomes included complete response rate (CRR), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Univariate logistic regression analyzed prognostic factors, and safety was assessed by comparing adverse events between groups. The ZR-CHOP group had a similar CRR of 75.0% compared to 67.5% in the control group and an ORR of 90.0% versus 97.5%. With a median follow-up of 26.5 months (range: 1–41), PFS and OS were analyzed. At 36 months, PFS was 61.9% in the ZR-CHOP group versus 63.8% in the control, while OS was 77.5% versus 76.7%. Among patients with MYD88/CD79B double mutations, the CRR was 90.0%. Elevated lactate dehydrogenase levels were linked to a lower likelihood of achieving a complete response. The most common treatment-related adverse events were infections (50%) and bleeding (15%) in the ZR-CHOP group. ZR-CHOP may improve outcomes in MYD88-mutated DLBCL, particularly in patients with MYD88/CD79B double mutations. Although further studies are needed, zanubrutinib shows promise as a targeted therapy in this population.

The online version contains supplementary material available at 10.1007/s00262-025-04090-4.

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