Zanubrutinib Monotherapy for Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pooled Analysis of Three Studies

Autor: Wei Xu, Shenmiao Yang, Constantine S. Tam, John F. Seymour, Keshu Zhou, Stephen Opat, Lugui Qiu, Mingyuan Sun, Tingyu Wang, Judith Trotman, Ling Pan, Sujun Gao, Jianfeng Zhou, Daobin Zhou, Jun Zhu, Yuqin Song, Jianda Hu, Ru Feng, Haiwen Huang, Dan Su, Miao Shi, Jianyong Li
Rok vydání: 2022
Předmět:
Zdroj: Advances in Therapy. 39:4250-4265
ISSN: 1865-8652
0741-238X
Popis: Zanubrutinib is a highly selective irreversible inhibitor of Bruton tyrosine kinase which has shown significant activity in lymphoid malignancies in early phase studies. We report here the long-term follow-up outcomes of zanubrutinib in various lines of therapy in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).This post hoc analysis pooled patients with treatment-naïve (TN) or relapsed/refractory (R/R) CLL/SLL receiving zanubrutinib monotherapy from three phase 1/2 studies (BGB-3111-1002, BGB-3111-AU-003, BGB-3111-205).A total of 211 patients with CLL/SLL (TN 19, R/R 192) were included. After weighting (TN 19, R/R 24), the overall response rate (ORR) was 95.4% and significantly higher in the TN group than in the R/R group (100 vs. 91.0%, p 0.0001). ORR was also significantly higher in the TN group than in the one prior line of therapy group (100 vs. 98.9%, p 0.0001). Among those with R/R disease, the ORR was 97.8% in patients with one prior line of therapy (n = 79) and 90.7% in those with 1 prior lines of therapy (n = 85; p = 0.080). The median follow-up times were 50.1, 35.7, and 45.9 months for TN, R/R and all cohorts, respectively. Progression-free survival and overall survival were significantly longer in the TN group and only one prior line of therapy group compared with the 1 prior lines of therapy group (all p 0.05) and were similar in the TN group compared with the one prior line therapy group. Efficacy was similar regardless of the presence of genomic aberrations. Most frequent grade ≥ 3 adverse events were infections (41.7%), neutropenia (34.1%), and thrombocytopenia (9.4%). Atrial fibrillation occurred in only 1.9% of patients.With extended follow-up, zanubrutinib yielded long-term benefits and demonstrated a favorable safety profile for patients with TN or RR CLL/SLL. Earlier utilization of zanubrutinib was associated with better outcomes.Clinical Trials.gov identifiers, NCT03189524, NCT02343120 (retrospectively registered), and NCT03206918 (retrospectively registered).
Databáze: OpenAIRE
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