(202) Real-World Comparative Evaluation of Ibrutinib, Acalabrutinib, and Zanubrutinib Tolerability in Patients with Chronic Lymphocytic Leukemia

Poster Abstract:

Background: Chronic lymphocytic leukemia (CLL) remains the most common type of chronic leukemia in adults. Over the last decade, the development of Bruton’s tyrosine kinase inhibitors (BTKi) have revolutionized frontline therapy. Although the use of second-generation BTKi have improved overall treatment tolerability; discontinuation rates due to toxicity, resistance, or progression remain present in real-world patients. Despite the notable results presented in trial participants, clinical trials may challenge the generalizability when applying care to a non-trial patient population. This study aims to assess the tolerability of BTKi in a real-world setting while overcoming the limitations of tightly controlled trials.

Objectives: The primary objective is to assess the time to first dose reduction or dose interruption due to toxicity. Secondary objectives include progression free survival (PFS), overall survival (OS), incidence of dose reductions, incidence of therapy interruption, and tolerability.

Methods: A single center, retrospective chart review of adult patients with CLL, who were initiated on ibrutinib, acalabrutinib, or zanubrutinib between January 1, 2020 to August 31, 2023 was performed to evaluate the differences in tolerability between agents in real-world patients at The University of Kansas Health System.

Results: One hundred fourteen patients were included in the final analysis. The median age at treatment initiation was 72 years (range, 41-92). Of these patients, 68 (59.6%) were male and 101 (88.6%) were Caucasian. At treatment initiation, 41 (35.9%) patients received ibrutinib, 56 (49.1%) received acalabrutinib, and 17 (12.1%) received zanubrutinib. The median duration of ibrutinib, acalabrutinib, and zanubrutinib therapy before first dose reduction or dose interruption due to toxicity was 205 (range, 5-1135), 252 (range, 8-1186), and 90.5 (range, 83-98) days, respectively. The incidence of dose reductions was 34%, 11%, and 6% (p = 0.004) with ibrutinib, acalabrutinib, and zanubrutinib, respectively. Incidence of at least one therapy interruption was 51%, 39%, and 17% (p = 0.059), with ibrutinib, acalabrutinib, and zanubrutinib, respectively. The most common reason for discontinuation was toxicity for ibrutinib (34.6%) and acalabrutinib (42.1%), while death unrelated to therapy was the only reason for zanubrutinib discontinuation (100%). PFS and OS results will be reported pending statistical analyses.

Discussion/

Conclusion: Real-world patients initiated on acalabrutinib or zanubrutinib have lower rates of dose reductions and therapy interruptions when compared to ibrutinib therapy. Results from this analysis support current literature surrounding the enhanced tolerability of selective BTK inhibitors. Additional conclusions will be based upon the results of statistical analyses.

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