Treatment-Emergent Cardiovascular Events Among Patients with Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) Treated with Bruton's Tyrosine Kinase Inhibitors (BTKi)

Background: The aim of this study was to describe treatment-emergent cardiovascular medical events (CV-E) among patients with CLL/SLL treated with acalabrutinib (acala) or zanubrutinib (zanu) in the community oncology setting. Methods: US adult patients diagnosed with CLL/SLL who initiated BTKi treatment between 01-Jan-2022 and 31-Dec-2023 were selected using the IntegraConnect PrecisionQ de-identified Database and followed between 01-Jan-2022 and 30-Apr-2024. Specific CV-E occurring after BTKi initiation were reviewed, with subanalyses performed for hypertension (HTN) and atrial fibrillation/flutter/arrythmia (Afib). Results: A total of 1476 patients were treated with acala (n=1039) or zanu (n=437) in the first-line setting. Overall, 142 (13.7%) patients in the acala group and 57 (13.0%) patients in the zanu group had a reported preexisting cardiac comorbidity during the year prior to BTKi initiation. Median follow-up from BTKi initiation was 13.1 (0.1, 27.4) months for the acala group and 7.9 (0.5, 25.8) months for the zanu group amongst patients treated in first-line setting. Among patients with at least 9, 12, or 15 months of follow-up who received acala (n=485, 384, and 274 respectively) or zanu (n=148, 72, and 33, respectively) in the first-line setting, the rate of treatment-emergent CV-E during the 9, 12, or 15 months after BTKi initiation was lower in the acala group (8.9%, 10.4%, and 11.0% respectively) than in the zanu group (12.2%, 15.3%, and 15.2%, respectively). The rate of treatment-emergent HTN was lower in patients receiving acala (5.2%, 5.7%, and 6.9%, respectively) compared to zanu (8.1%, 9.7%, and 9.1%, respectively) in patients with at least 9, 12, or 15 months of follow-up. The rate of treatment-emergent Afib was similar in patients receiving acala (3.1%, 4.2%, and 4.0%, respectively) and zanu (2.7%, 4.2%, and 6.1%, respectively) in patients with at least 9, 12, or 15 months of follow-up. A total of 386 patients were treated with acala (n=230) or zanu (n=156) in the second-line or later setting. Overall, 37 acala (16.1%) patients and 23 zanu (14.7%) patients had a preexisting cardiac comorbidity during the year prior to BTKi initiation. Median follow-up from BTKi initiation was 13.7 (0.3, 27.2) months for the acala group and 8.1 (0.5, 25.3) months for the zanu group amongst patients treated in second-line or later setting. Among patients with at least 9, 12, or 15 months of follow-up who received acala (n=101, 76, and 57, respectively) or zanu (n=51, 26, and 18, respectively) in the second line of therapy or later, the rate of treatment-emergent CV-E during the 9, 12, or 15 months after BTKi initiation was lower in the acala group (14.9%, 14.5%, and 12.3%, respectively) than in the zanu group (33.3%, 30.8%, and 33.3%, respectively). The rate of HTN was lower in patients receiving acala (7.9%, 7.9%, and 8.8%, respectively) compared to zanu (21.6%, 19.2%, and 16.7%, respectively) in patients with at least 9, 12, or 15 months of follow-up. The rate of Afib was lower in patients receiving acala (6.9%, 6.6%, and 5.3%, respectively) than zanu (13.7%, 11.5%, and 16.7%, respectively) in patients with at least 9, 12, or 15 months of follow-up. Conclusions: In first-line therapy, a lower percentage of patients who received acala experienced treatment-emergent CV-E, including HTN, compared to those who received zanu. In second-line therapy or beyond, a lower percentage of patients who received acala experienced treatment-emergent CV-E, including HTN and Afib, compared to those who received zanu.