American Journal of Hematology (AJH): Orelabrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Patients: Multi-center, Single-arm, Open-label, Phase 2 Study



Orelabrutinib is a novel, small molecule, selective irreversible Bruton's tyrosine kinase inhibitor. The aim of this study was to evaluate the efficacy and safety in patients with refractory or relapsed chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). 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 evaluated by an independent review committee was the primary endpoint, and secondary endpoints include progression-free survival, overall survival, and safety. Independent review committee assessed overall response rate 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, the median progression-free survival had not been achieved, while the 30-month progression-free survival rate and overall survival rates 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: overall response rates of patients carrying positive TP53 mutational status or del(17p), del(11q), as well as unmutated immunoglobulin heavy-chain variable region gene were 100%, 94.7%, and 93.9%, respectively. Most adverse events 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. In conclusion, Orelabrutinib demonstrated compelling efficacy as well as safety profiles, with a noteworthy number of patients obtaining complete response in refractory or relapsed CLL/SLL.


InnoCare Pharma Limited sponsored this study and was responsible for medical monitoring. Shuo Ma, Xinran Tang and Bin Zhang are employees of InnoCare Pharma Limited. The other authors declared that they have no conflict of interest.

Open Research


Additional information is reported in the supplementary materials. The sharing of individual participant data may be provided by reasonable request. Please contact the corresponding author.

Supporting Information

ajh26826-sup-0001-Supinfo.docxWord 2007 document , 197.8 KBFigure S1. Structure of orelabrutinibFigure S2. Best overall response at different follow-up times (assessed by IRC)Figure S3. Best percent change in sum of the products of diameters (SPD) of target lesions and corresponding response evaluation (assessed by IRC). Abbreviation: CR, complete response. IRC, independent review committee. PD, Progressive disease. PR, partial response. PR-L, partial response with lymphocytosis. SD, stable disease. SPD, sum of the products of diameters.Figure S4. Subgroup analysis of ORR (assessed by IRC)Figure S5. Kaplan-Meier plot of PFS and DOR by best overall response (assessed by IRC). (A) Progression-free survival in CR/CRi, others and overall. (B) Duration of response. (C) Progression-free survival in CR/CRi and PR/PR-L. Abbreviation: CR, complete response. CRi, complete response with incomplete bone marrow recovery. IRC, independent review committee. PR, partial response. PR-L, partial response with lymphocytosis.Table S1. Screen Failure CasesTable S2. Efficacy outcomesTable S3. Overview of TEAEs/TRAEsTable S4. Serious TEAEsTable S5. Summary of deaths
ajh26826-sup-0002-AppendixS1.docxWord 2007 document , 659.5 KBAppendix S1. Supplementary information.

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.


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