Orelabrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Patients: Multi-center, Single-arm, Open-label, Phase 2 Study

Background: Orelabrutinib is a novel, small molecule, selective irreversible Bruton’s tyrosine kinase inhibitor. The aim of this study was to evaluate the efficacy as well as safety in patients with refractory or relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (R/R CLL/SLL). Methods: This is single-arm, multi-center, open-label, phase 2 study in 80 eligible Chinese patients, who were treated with monotherapy of orelabrutinib at 150 mg once daily. Overall response rate (ORR) that was evaluated by an independent review committee (IRC) was set as the study’s primary endpoint, with progression-free survival (PFS), overall survival (OS), and safety as the study’s major secondary endpoints. Results: IRC-assessed ORR was 92.5% (74/80); complete response 21.3% (17/80), partial response 60.0% (48/80), partial response with lymphocytosis 11.3% (9/80). At a 32.3-month median follow-up (mFu), the median PFS had not been achieved, while the 30-month PFS rate and OS rate were 70.9% (95% confidence interval [CI], 59.5-79.6) and 81.3% (95% CI, 70.8-88.2), respectively. Orelabrutinib also revealed substantial response in patients with high prognostic risks: ORRs of patients carrying positive TP53 mutational status or del(17p), del(11q), as well as unmutated immunoglobulin heavy-chain variable region gene ( IGHV ) were 100%, 94.7%, and 93.9%, respectively. Most adverse events (AEs) were in low grade, with 86.8% of AEs being Grade 1 or 2. Nearly 67% of patients were still receiving orelabrutinib after almost a 3-year follow-up. Conclusions: Orelabrutinib demonstrated compelling efficacy as well as safety profiles, with a noteworthy number of patients obtaining complete response in R/R CLL/SLL. Trial registration The study (NCT03493217) has been registered at ClinicalTrials.gov.