Zanubrutinib plus R-CHOP for the treatment of newly diagnosed double-expressor lymphoma: A phase 2 clinical study.

BACKGROUND: Double-expressor lymphoma (DEL) has a poorer prognosis than other subtypes of diffuse large B-cell lymphoma (DLBCL). This study is a multicenter, prospective, single-arm, phase 2 clinical study initiated by investigators to evaluate the efficacy and safety of combined zanubrutinib with R-CHOP, which includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone for patients with DEL (stage II or more), as well as to explore factors related to efficacy preliminarily.

METHODS: From November 2020 to July 2022, 48 newly diagnosed patients were enrolled. All patients received twice-daily oral zanubrutinib (160 mg) for 6 months and standardized R-CHOP regimen for six to eight cycles.

RESULTS: The objective response rate (ORR) was 89.6%, with a complete response rate (CRR) of 83.3%. The median follow-up was 29.3 months. The median progression-free survival (PFS) and overall survival (OS) were not reached. The PFS and OS were 81.25% and 93.75% at 2 years, respectively. Grade ≥3 adverse events (AEs) were reported in 23 of 48 (47.9%) patients. Next-generation sequencing (NGS) results of 33 patients showed that TP53, MYD88, and PIM1 were the most common mutated gene. Multivariate analysis revealed that BCL-6 gene rearrangement was an adverse prognostic factor for both PFS (hazard ratio [HR], 0.247; 95% confidence article [CI], 0.068-0.9; p = .034) and OS (HR, 0.057; 95% CI, 0.006-0.591; p = .016), whereas the number of extranodal involvements also significantly influenced OS (HR, 15.12; 95% CI, 1.07-213.65; p = .044).

CONCLUSIONS: Zanubrutinib in combination with R-CHOP is an effective option for DEL patients, and the toxicity of zanubrutinib is entirely acceptable for patients.