CLL-390 Persistence and Time to Next Treatment With Ibrutinib Treatment in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Including Patients at High Risk for Atrial Fibrillation or Stroke: A Real-World Study

Context: Atrial fibrillation (AF) is a recognized adverse consequence associated with all Bruton's tyrosine kinase inhibitors used to treat chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL); however, real-world time to discontinuation (TTD) and time to next treatment (TTNT) of CLL/SLL patients with a high baseline AF risk remain unknown. Objective: To describe TTNT and TTD for CLL/SLL patients who initiated a first-line (1L) or second-or-later-line (2L+) therapy with ibrutinib or other regimens, in all patients and for subsets of patients with high baseline risk of AF/AF-related events. Methods: Patients with CLL/SLL from the nationwide Electronic Health Record-derived database (02/12/2013–01/31/2021) initiating 1L or 2L+ treatment with ibrutinib or other regimens (e.g., chemoimmunotherapy, other novel targeted agents including acalabrutinib) on or after 02/12/2014 (index date) were analyzed. For each setting (1L and 2L+) and index regimen, Kaplan–Meier survival analysis assessed TTD and TTNT among all patients, patients with high risk of AF (CHARGE-AF risk score ≥10.0%), and patients at high risk of AF-related events (CHA2DS2-VASc risk score ≥3 [female patients] or ≥2 [male patients]). Results: A total of 2,190 (20.0%/49.3% high risk CHARGE-AF/CHA2DS2-VASc) and 1,851 (17.5%/44.5% high risk CHARGE-AF/CHA2DS2-VASc) patients received ibrutinib in 1L and 2L+, respectively, whereas 4,388 (15.6%/44.3% high risk CHARGE-AF/CHA2DS2-VASc) and 4,135 (20.8%/50.5% high risk CHARGE-AF/CHA2DS2-VASc) patients were treated with other regimens in 1L and 2L+, respectively. The mean TTD for ibrutinib was similar regardless of AF-related risk (1L: all patients, 20.0 months; high AF risk, 16.1 months; high risk of AF-related events, 18.0 months; similar results in 2L+). Median TTNT was significantly longer for ibrutinib versus other regimens (1L: not reached vs. 45.9 months; 2L+: not reached vs. 23.6 months; both P<0.05), including among those with high AF-related risk. TTNT was similar between all patients and high-risk cohorts in 1L and 2L+ (all P>0.05). Conclusions: This study demonstrates the real-world use of ibrutinib in patients at high baseline risk of AF/AF-related events and highlights that baseline AF-related risk does not adversely impact TTD and TTNT associated with ibrutinib use in CLL/SLL patients. In addition, TTNT was significantly longer for patients treated with ibrutinib-based regimens than other regimens.