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Updated: Aug 13, 2025
Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
Orelabrutinib in relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma patients:
Wei Xu1, Keshu Zhou2, Tingyu Wang3
1Department of Hematology, Pukou CLL Center, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, People's Republic of China.
Abstract:
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.
Insights
Orelabrutinib shows high efficacy and safety in treating refractory or relapsed chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). The Bruton's tyrosine kinase inhibitor achieved a 92.5% overall response rate in a Phase 2 study.
Area of Science:
- Oncology
- Pharmacology
Background:
- Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) is a B-cell malignancy.
- Refractory or relapsed CLL/SLL presents significant treatment challenges.
Purpose of the Study:
- To evaluate the efficacy and safety of orelabrutinib in patients with refractory or relapsed CLL/SLL.
- To assess the overall response rate, progression-free survival, and overall survival.
Main Methods:
- A single-arm, multi-center, open-label, Phase 2 study.
- 80 eligible Chinese patients received orelabrutinib monotherapy at 150 mg once daily.
- Primary endpoint: Overall response rate (ORR) by independent review committee.
Main Results:
- ORR was 92.5% (74/80), with 21.3% complete response and 60.0% partial response.
- Median progression-free survival was not reached at 32.3-month follow-up; 30-month PFS rate was 70.9%.
- High response rates observed in high-risk subgroups (TP53, del(17p), del(11q), unmutated IGHV).
Conclusions:
- Orelabrutinib demonstrates compelling efficacy and a favorable safety profile in refractory/relapsed CLL/SLL.
- A significant proportion of patients achieved complete response.
- The drug shows sustained efficacy and tolerability, with 67% of patients continuing treatment after nearly 3 years.
