Long-term cardiovascular outcomes in patients with lymphoma who had early post-CAR-T cardiovascular events: A multi-center, international study

Abstract Introduction: CAR-T is associated with a spectrum of acute toxicities, including acute cardiovascular events (CVE). The long-term cardiovascular outcomes after acute CVEs are not fully understood. Methods: We retrospectively studied adult patients with lymphoma who received CAR-T therapy from 2018-2024 at 5 international centers. We identified a cohort of patients who experienced an early acute CVE, defined as occurring from lymphodepletion through 30 days post-infusion. To assess long-term outcomes, patients who died within 30 days of infusion were excluded. CVEs were defined as arrhythmias [atrial fibrillation (Afib), atrial flutter, supraventricular tachycardia (SVT), ventricular arrhythmia, bradyarrhythmia], clinical heart failure (CHF), acute coronary syndrome, pericardial effusion, new onset valvular regurgitation, or cerebrovascular accident (CVA). At each site, a cardiologist adjudicated any complex cases. Patients who experienced more than one distinct early CVE were classified as having a single early CVE. Data on long-term cardiovascular outcomes were collected from medical records until death or last known follow-up. Results: Of the 785 patients with lymphoma who were treated with CAR-T, 66 (8.4%) experienced an early acute CVE and survived >30 days. Median follow-up for patients with an early acute CVE was 33.6 months (25.0-45.1). Median age was 70 years, 65% were male and 76% had Large B-Cell Lymphoma, 20% had Mantle Cell Lymphoma and 4% had Follicular Lymphoma. 69% of patients had 3 or fewer lines of treatment before CAR-T. At the time of CAR-T infusion, 62% had progression of disease and 24% were in partial remission. Axicabtagene ciloleucel was most common product (41%), followed by Tisagenlecleucel (26%), Brexucabtagene autoleucel (20%), and Lisocabtagene maraleucel (14%). 71% of patients had a pre-CAR-T Karnofsky performance status <90. Key baseline comorbidities included hypertension (56%), Afib (39%), diabetes (21%), coronary artery disease (14%), CHF (14%), SVT (8%), stroke (6%). The median time to first early CVE was 5 days after CAR-T infusion (IQR 3.8-7 days). The most common early CVEs were Afib (n=32), SVT (n=12), CHF (n=9), and ventricular arrhythmias (n=4). Of the 32 patients with early Afib, 13 (41%) were newly diagnosed. Of the 9 patients with acute CHF, 6 (67%) were newly diagnosed. Of the 9 patients with SVT, 8 (89%) were newly diagnosed. In this cohort of high-risk patients, 15/66 (23%) experienced at least one late CVE. Of those, 6 had Afib, 3 had atrial flutter (of which one patient also had a ventricular arrhythmia), 2 had CHF, 2 had SVT, 1 had a CVA, and 1 had new onset valvular regurgitation. Compared to the 51 patients with no late CVEs, the 15 patients who had late CVEs had higher rates of preexisting cardiac conditions. No cases of acute coronary syndrome were recorded in the late period. 37 patients died during our follow-up period; the cause of death for 26 (70%) was relapse/progression of disease. Conclusions: About 8% of patients had an acute CVE within 30 days of CAR-T. While most patients remained free of subsequent events, 23% of these survivors experienced a late CVE. Afib was the dominant CVE, both early and late. Further comparative studies are needed to determine the relative risk of late events compared to patients without early CVEs.