Introduction: Standard of care (SOC) Anti-CD19 chimeric antigen receptor (CAR) T-cell therapies such as axicabtagene ciloleucel (axicel) and tisagenlecleucel (tisa-cel) are associated with cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS). There is limited information available about cardiovascular (CV) events associated with SOC axi-cel or tisa-cel. In the clinical trials leading to their FDA approval, patients with CV comorbidities, organ dysfunction, or lower performance status were often not included. An improved understanding of CV toxicities in the real-world setting will better guide therapy selection and management of patients receiving these cellular therapies. Method(s): We retrospectively reviewed the characteristics and outcomes of adult patients with relapsed/refractory large B-cell lymphoma treated with SOC axi-cel or tisa-cel between 01/2018 and 4/ 2020 at MD Anderson Cancer Center. Major adverse CV events within 30 days after infusion (30-d MACE) included arrhythmias requiring intervention (ARI), new cardiomyopathy (NCMP), exacerbation of heart failure (HF), cerebrovascular accident (CVA), myocardial infarction (MI), or CV death. MACE, CRS, and ICANS were treated per institutional standards. Result(s): One-hundred and sixty-five patients were included in the analysis, and baseline characteristics are shown in the Table. Overall, 16% of patients developed at least one 30-d MACE: 60.6% ARI (atrial fibrillation/flutter 40.7%, non-sustained ventricular tachycardia 40.7%), 12.1% EHF, 12.1% CVA, 6.1% MI, 6.1% NCMP, and one patient died due to MI. The first 30-d MACE occurred in a median of 7 days (range 0-29) after CAR-T cell infusion. Moreover, 6 patients had one recurrence of 30-d MACE (2 EHF, 2 ARI, and 2 CVA), and 3patients experienced two recurrences of 30-d MACE (1 ARI and 2 NCMP). As displayed in the Table, age >60 years, baseline echocardiographic diastolic dysfunction, earlier start of CRS, CRS >= grade 3, long duration of CRS, and use of tocilizumab were significantly associated with an increased risk of 30-d MACE. No association between timing and/or magnitude of C-reactive protein or ferritin peak and occurrence of MACE was observed. After a median follow-up time of 16.2 months (range 14.3-19.1) for censored observations, the occurrence of 30-d MACE was not significantly associated with progression-free survival (PFS) (p-value = 0.55, log-rank test), or with overall survival (OS) (p-value = 0.52, log-rank test). Conclusion(s): Our results suggest that the occurrence of 30-d MACE is more frequent among patients who are elderly, with baseline diastolic dysfunction, early, severe and prolonged CRS, but had no statistically significant impact on PFS and OS. However, with limited follow-up, larger prospective studies are needed, and multidisciplinary management of these patients is recommended.
CITATION STYLE
Steiner, R., Banchs, J., Koutroumpakis, E., Becnel, M., Gutierrez, C., Strati, P., … Deswal, A. (2021). CARDIOVASCULAR EVENTS AMONG ADULT PATIENTS WITH AGGRESSIVE B‐CELL LYMPHOMA TREATED WITH STANDARD OF CARE AXICABTAGENE CILOLEUCEL AND TISAGENLECLEUCEL. Hematological Oncology, 39(S2). https://doi.org/10.1002/hon.177_2880
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