Zanubrutinib combined with R-CHOP in previously untreated diffuse large B-cell lymphoma with specific gene...

Area of Science:

• Oncology
• Hematology
• Genetics

Background:

• Diffuse large B-cell lymphoma (DLBCL) exhibits significant clinical heterogeneity.
• Standard R-CHOP therapy yields suboptimal outcomes for DLBCL patients with high-risk genomic alterations (e.g., MYD88, CD79B, NOTCH1, TP53 mutations, MYC rearrangements).
• Aberrant BCR signaling is implicated in high-risk DLBCL, suggesting potential sensitivity to Bruton's tyrosine kinase (BTK) inhibitors.

Purpose of the Study:

• To evaluate the efficacy and safety of zanubrutinib combined with R-CHOP (ZR-CHOP) in the frontline treatment of previously untreated DLBCL patients with specific high-risk molecular features.
• To assess treatment response, progression-free survival (PFS), and overall survival (OS) in this molecularly selected patient cohort.

Main Methods:

• A prospective, single-center, phase II clinical trial was conducted.
• 59 previously untreated DLBCL patients (aged 18-75) with high-risk molecular features received one initial R-CHOP cycle followed by five cycles of ZR-CHOP.
• Response was evaluated using Lugano 2014 criteria, with a primary endpoint of 3-year PFS.

Main Results:

• The overall response rate (ORR) was 91.4% (53/58), with a complete metabolic response (CMR) rate of 79.3% (46/58).
• After a median follow-up of 30.1 months, the estimated 3-year PFS was 80.3% and 3-year OS was 89.1%.
• The MCD-like subgroup showed a 100% 3-year OS, while the N1-like subgroup had poorer survival (2-year OS 33.3%).

Conclusions:

• ZR-CHOP demonstrates encouraging efficacy and an acceptable safety profile in molecularly selected high-risk DLBCL patients.
• The MCD-like subgroup exhibited particularly favorable responses and survival outcomes.
• Further investigation is warranted to optimize treatment strategies for different molecular subtypes of DLBCL.