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Orelabrutinib Monotherapy Found Effective For Patients With R/R CLL/SLL
Findings from an updated study have further confirmed that orelabrutinib is effective in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL); these data were presented at the 2021 American Society of Hematology (ASH) Annual Meeting.
“Orelabrutinib is a novel and highly selective irreversible Bruton tyrosine kinase (BTK) inhibitor. It was approved in China for the treatment of patients with R/R CLL, SLL. We previously reported that orelabrutinib had high bioavailability with ~100 percent BTK occupancy at 24 hours at 150mg daily dosing regimen, and had demonstrated excellent safety and efficacy profiles in a phase 2 trial of R/R CLL/SLL,” said Dr Wei Xu, Department of Hematology, Pukou CLL Center, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China, and co-investigators.
Thus, Dr Xu et al reported on updated long-term results of the open-label, multicenter, phase 2 study, which evaluated the safety and efficacy of orelabrutinib 150mg oral daily dose in 80 patients with R/R CLL/SLL. All patients (median age 60) received ≥1 prior treatment. The patient population included 70 percent with Rai stage III-IV disease, 22.5 percent with a del(17p) and/or a TP53 mutation, 41.3 percent with unmutated immunoglobin heavy chain variable region (IGHV), and 23.8 percent with a del(11q) mutation.
Responses were assessed per 2008 IWCLL criteria with modification for PR with lymphocytosis (PR-L) or the Lugano Classification for CLL and SLL, respectively.
The median follow-up time was 31.2 months, with 68.8 percent of patients remaining on the treatment. The overall response rate (ORR) was 93.8 percent (95% CI, 86.01%-97.94%) and was generally consistent across all subgroups, including those with unfavorable prognostic factors. Out of all patients, 23.8 percent had a complete response (CR), 2.5 percent had incomplete marrow recovery (CRi), 56.8 percent had a partial response (PR), and 11.3 percent had a PR with lymphocytosis (PR-L). The median time it took for patients to achieve a first response was 1.84 months. The median duration of response (DOR) and progression-free survival (PFS) were not met. However, the estimated DOR was 70.6 percent, and the 30-month PFS was 70.9 percent.
Comparing to the study’s previous CR/CRi rate of 8.8 percent at a median follow-up of 14.3 months, the updated CR/CRi rate reached 26.3 percent.
“Orelabrutinib showed a significant higher CR/CRi rate in R/R CLL/SLL in comparison with other BTK inhibitors at a similar median follow-up period,” noted Dr Xu et al.
The extended follow-up demonstrated no emerging safety concerns. Similar to the previously reported safety results, most adverse events (AEs) were mild to moderate. The most common (any grade >30%) included neutropenia, thrombocytopenia, upper respiratory tract infection, and urine red blood cells positive. There were no cases of atrial fibrillation or secondary malignancy, and no patient experienced grade ≥3 hypertension. Only 1 patient had grade ≥3 diarrhea, and 2 patients had major hemorrhage. There were 2 patients who discontinued treatment related to AEs, and 5 patients reported dose reductions related to AEs.
“This updated study result further confirms that orelabrutinib is efficacious in treating R/R CLL patients with significant higher CR rate than other BTK inhibitors, durable response and improved safety profiles. Orelabrutinib provides a favorable therapeutic choice for patients with R/R CLL/SLL and has great potential to be the best candidate for the combination therapy,” concluded Dr Wu et al.—Emily Bader
Xu W, Song Y, Wang T, et al. Orelabrutinib Monotherapy in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Updated Long Term Results of Phase II Study. Presented at: the 2021 ASH Annual Meeting; Dec. 11-14; 2021; Abstract 2638.
