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Elevated Risk of Atrial Fibrillation or Stroke in Patients With CLL Receiving Ibrutinib Treatment Has Minimal Impact on TTNT and TTD
A group of researchers investigated whether a high baseline risk of atrial fibrillation (AF) or stroke in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) has an effect on time to next treatment (TTNT) or time to discontinuation (TTD). The study included patients receiving first-line (1L) or second or later line (2L+) ibrutinib or other CLL/SLL treatment regimens (Clin Lymphoma Myeloma Leuk. 2022; 22(11):e959-e971. doi: 10.1016/j.clml.2022.07.004).
For patients with CLL/SLL, the use of oral targeted therapies such as Bruton’s tyrosine kinase inhibitors (BTKis), including ibrutinib and acalabrutinib, in real-world patient populations has confirmed the long-term efficacy and safety profile of these treatments. However, BTKis have been associated with cardiovascular (CV) events such as AF and hypertension.
“While CLL/SLL patients have a high baseline risk of AF, little is known about the effect this may have on real-world outcomes among patients treated with BTKis,” wrote Anna Narezkina, MD, University of California San Diego Health, San Diego, CA, and colleagues.
For this study, the researchers used the Cohorts for Aging and Research in Genomic Epidemiology-AF (CHARGE-AF) and CHA2DS2 -VASc risk scores to assess the patients’ risk of developing AF and stroke, respectively. They also utilized the Flatiron Health Electronic Health Record (EHR) deidentified database to select patients with CLL/SLL from approximately 280 US cancer clinics at community and academic medical centers (approximately 800 sites of care) who were actively receiving any line of therapy between February 12, 2014, and January 31, 2021. Kaplan-Meier survival analysis was used to assess TTD and TTNT among all patients, patients with high AF risk (CHARGE-AF risk score ≥ 10.0%), and patients at high risk of stroke (CHA2DS2-VASc risk score ≥ 3 [females] or ≥2 [males]).
For 1L and 2L+ treatment, 2190 and 1851 patients received ibrutinib, respectively, and 4388 and 4135 were treated with other regimens. The study found that regardless of baseline risk of AF or stroke, most of the patients remained on ibrutinib at 12, 24, and 36 months and had a longer median TTNT than those treated with other regimens (1L: not reached vs 45.9 months; 2L+: not reached vs 23.6 months; both P < .05). In 1L or 2L+ treatment, TTNT was similar between all the cohorts (all patients, high-risk AF, and high-risk stroke) receiving ibrutinib and between those receiving other regimens (P ≥ .05 for all). In addition, TTD was not affected by patients’ baseline risk of AF or stroke, and the median TTD for ibrutinib was similar regardless of AF- or stroke-related risk (1L: all patients, 15.7 months; high AF risk, 11.7 months; high stroke risk, 13.7 months; similar results in 2L+).
The results suggest that “BTKi-associated AF can and is being successfully managed (eg, with cardiology or cardio-oncology involvement), thereby allowing continued use of ibrutinib in these patients,” wrote Dr Narezkina and colleagues.
The authors acknowledged that the study had several limitations, which included that the EHR data may contain omissions or inaccuracies; the Flatiron Health database does not capture all comorbidity information, which could have affected available treatment information and accuracy of the number of patients with high CHARGE-AF and CHA2DS2-VASc because these calculations take comorbidities into consideration; and the results from the database mostly consist of information from community-based medical practices, which may not be applicable to other populations.
Based on their findings, the authors suggest that even patients with CLL/SLL who have a high risk of AF or stroke can benefit from using ibrutinib and can continue this treatment along with implementing strategies to manage BTKi-associated adverse CV events.
