Healthcare Resource Utilization and Costs in Patients with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Treated with Covalent Btki (cBTKi): Real-World Impact of Cardiovascular Adverse Events
Authors: Obeng-Kusi Mavis , De Nigris Enrico , Leng Siyang , Farooqui Mohammed Z. H. , Yapici Halit O. , Weimer Ian , Jiao Weiqi , Hyatt Hayden W. , Zhang Xuan , Lodaya Kunal , Dingli David 
Published: December 2024

Background:
Although Covalent BTKis have revolutionized treatment of CLL/SLL, cardiotoxicity is a known side effect, which can increase the total costs to the healthcare system. This study evaluated the real-world healthcare resource utilization (HCRU) and costs in patients who did and did not experience incident cardiovascular adverse events (CVAEs) during cBTKi treatment.
Methods:
Adult patients diagnosed with CLL/SLL who initiated ibrutinib or acalabrutinib treatment (index date) between 2020-2023 in the United States were identified using claims data from Optum's de-identified Clinformatics® Data Mart Database and followed up to 36 months post-index. Patients were stratified into two cohorts based on the presence of an incident CVAE during treatment with index cBTKi, defined as the occurrence of a CVAE not present in a patient's medical history. HCRU and costs were evaluated on a per 1,000 patient-months basis. Z tests and univariate gamma general linear models were used to compare HCRU and cost rates. HCRU between those who received ibrutinib or acalabrutinib were also assessed.
Results:
Overall, 2,069 eligible patients were identified with a mean ± SD age of 73.7 ± 9.1 years, and 40.4% were female. The mean ± SD [median] treatment-specific observation period was 11.4 ± 9.5 [8.5] months. Of the total cohort, 442 (21.4%) experienced at least one incident CVAE, while 1,627 patients (78.6%) experienced no CVAEs. Among those without a pre-index history of the specific CV AE of interest, the proportion of patients with incident events were 21.4% for hypertension, 9.8% for atrial fibrillation, 9.2% for atrial flutter, and 9.6% for ventricular arrhythmias.
Patients who experienced an incident CVAE had 4,334 total days with medical service compared to 3,138 days in those who did not (p&lt;0.001). The drivers of differences in total medical service days between those with and without CVAEs were inpatient days (690 vs 230), followed by outpatient days (2,798 vs 2,425), other visits (e.g., hospice; 662 vs 375), and emergency room (ER) visits (184 vs 109). Total days with medical service were 3,458 in those who received ibrutinib and 3,410 with acalabrutinib.
Total healthcare cost rates in those who experienced an incident CVAE were $20,250,560 compared to $17,413,460 in those without CVAEs (p&lt;0.001). Inpatient costs drove differences in total costs between those with CVAEs and those without ($3,417,948 vs $915,839, p&lt;0.001), followed by outpatient ($2,415,060 vs $1,769,628, p&lt;0.01) and ER costs ($186,820 vs $87,585, p&lt;0.001). Pharmacy costs were the largest contributor to total cost rates for both cohorts ($14,016,900 for those with a CVAE vs $14,473,270 without any CVAEs, p&lt;0.001).
Regarding specific incident CVAEs, the cost difference in total costs between those with and without the event were $3,789,820 for atrial fibrillation (higher in those with the event), $3,867,160 for atrial flutter, $3,674,860 for ventricular arrhythmias, and $721,840 for hypertension. Inpatient costs were the largest driver in total cost differences between those with and without the specific CVAE of interest; inpatient cost differences were $3,255,699 higher in those with atrial fibrillation, $3,436,913 with atrial flutter, and $3,299,371 with ventricular arrhythmia. For hypertension, pharmacy costs drove differences in total costs and were $346,570 higher in those with the CVAE.
Summary/Conclusion:
Overall, the economic burden remains high in patients treated for CLL/SLL, especially in cBTKi patients experiencing an incident CVAE. These findings highlight the importance of careful treatment selection, safety monitoring, and early management of CVAEs in order to improve patient outcomes and reduce the downstream impacts on healthcare resources and costs.