Efficacy of BTK inhibitor combined with rituximab and lenalidomide in newly diagnosed diffuse large B-cell lymphoma: a single-center, retrospective study.

The Smart Start trial demonstrated the combination of ibrutinib, rituximab, and lenalidomide resulted in impressive efficacy in newly diagnosed non-GCB diffuse large B-cell lymphoma (DLBCL). However, ibrutinib was associated with increased unexpected toxicity in elderly patients. Zanubrutinib and orelabrutinib have better target selectivity. This single-center, real-world, off-label study retrospectively included patients with newly diagnosed DLBCL who received SMART regimen (rituximab, lenalidomide plus BTK inhibitor) between January 2021 and June 2024. The outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. A total of 84 patients were analyzed for efficacy with a median follow-up of 13.5 (range, 2.5-42.2) months. The OR2 regimen (orelabrutinib, rituximab and lenalidomide) was administered to 60.7% (51/84) patients, and ZR2 regimen (zanubrutinib, rituximab and lenalidomide) to 39.3% (33/84) patients. The median PFS was 32.4 months, with PFS rates of 85.3% at 1-year, and 63.3% at 2-year. Median OS was not reached, with the estimated 1-, 2- and 3-year OS rates of 93.4%, 85.1%, and 84.7%, respectively. Fifty-one (60.7%) patients reported grade ≥ 3 adverse events, with the most common being neutropenia (54.8%). This real-world data support SMART regimen as a potential treatment option for DLBCL patients, with promising efficacy and acceptable safety.