Orelabrutinib in relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma patients: Multi‐center, single‐arm, open‐label, phase 2 study

Abstract

BackgroundOrelabrutinib is a novel, small molecule, selective irreversible Bruton's tyrosine kinase inhibitor. The aim of this study was to evaluate the e cacy as well as safety in patients with refractory or relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (R/R CLL/SLL). MethodsThis 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. ResultsIRC-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% con dence 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. ConclusionsOrelabrutinib demonstrated compelling e cacy as well as safety pro les, with a noteworthy number of patients obtaining complete response in R/R CLL/SLL.

Bruton’s tyrosine kinase inhibition for the prevention of anaphylaxis: an open-label, phase 2 trial

“…Interestingly, many of these side-effects are thought to be due to off-target effects, and could theoretically be avoided by the use of compounds with higher speci city for BTK. Encouragingly, next-generation BTK inhibitors that are currently in development for chronic urticaria and autoimmune diseases are more selective for BTK with fewer off-target effects, and therefore show more favorable sideeffect pro les [22][23][24][25] . For example, 12 weeks of remibrutinib (manufacturer: Novartis) was well-tolerated in a phase 2 trial for chronic urticaria with no observed bleeding, arrhythmia, or hypertension events in the treatment arms 22 , as well as during the open-label extension of this trial for up to 52 weeks.…”

A pilot study of orelabrutinib treatment in three cases of refractory/relapsed autoimmune haemolytic anaemia/Evans syndrome

“…Orelabrutinib is a novel BTK inhibitor, 12 which is effective in the treatment of small B‐cell lymphoma, 13 central nervous system lymphoma 14 and Fahrenheit macroglobulinaemia 15 . Although ibrutinib has been applied to several autoimmune diseases, there is no relevant data on orelabrutinib yet.…”

Orelabrutinib for the treatment of relapsed or refractory marginal zone lymphoma: A phase 2, multicenter, open‐label study

“…Orelabrutinib is a novel, oral, and covalent next‐generation BTK inhibitor with high target selectivity. Orelabrutinib has shown favorable efficacy and safety in other B cell malignancies and has been approved in China for the treatment of r/r chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and r/r mantle cell lymphoma (MCL) 11,12 . To further investigate the efficacy and safety of orelabrutinib in MZL, we conducted a phase 2, multicenter, open‐label clinical trial of orelabrutinib monotherapy in patients with r/r MZL, which was the first pivotal trial of a BTK inhibitor treating r/r MZL patients conducted in China.…”