Cardiovascular Events in Patients Treated With Chimeric Antigen Receptor T-cell Therapy for Aggressive B-cell Lymphoma

Authors

Raphael E Steiner
Jose Banchs
Efstratios Koutroumpakis
Melody Becnel
Cristina Gutierrez
Paolo Strati
Chelsea C Pinnix
Lei Feng
Gabriela Rondon
Catherine Claussen
Nicolas Palaskas
Kaveh Karimzad
Sairah Ahmed
Sattva S Neelapu
Elizabeth Shpall
Michael Wang
Francisco Vega
Jason Westin
Loretta J Nastoupil
Anita Deswal

Publication Date

7-1-2022

Journal

Haematologica

Abstract

Standard of care (SOC) chimeric antigen receptor (CAR) T-cell therapies such as axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are associated with multisystem toxicities. There is limited information available about cardiovascular (CV) events associated with SOC axi-cel or tisa-cel. Patients with CV comorbidities, organ dysfunction, or lower performance status were often excluded in the clinical trials leading to their Food and Drug Adminsitration approval. An improved understanding of CV toxicities in the real-world setting will better inform therapy selection and management of patients receiving these cellular therapies. Here, 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. Among the 165 patients evaluated, 27 (16%) developed at least one 30-day (30-d) major adverse CV event (MACE). Cumulatively, these patients experienced 21 arrhythmias, four exacerbations of heart failure/cardiomyopathy, four cerebrovascular accidents, three myocardial infarctions, and one patient died due to myocardial infaction. Factors significantly associated with an increased risk of 30-d MACE included age ≥60 years, an earlier start of cytokine release syndrome (CRS), CRS ≥ grade 3, long duration of CRS, and use of tocilizumab. After a median follow-up time of 16.2 months (range, 14.3-19.1), the occurrence of 30-d MACE was not significantly associated with progression-free survival or with overall survival. Our results suggest that the occurrence of 30-d MACE is more frequent among patients who are elderly, with early, severe, and prolonged CRS. However, with limited follow-up, larger prospective studies are needed, and multidisciplinary management of these patients is recommended.

Keywords

Adult, Aged, Antigens, CD19, Cardiovascular Diseases, Cell- and Tissue-Based Therapy, Humans, Immunotherapy, Adoptive, Lymphoma, Large B-Cell, Diffuse, Middle Aged, Receptors, Antigen, T-Cell, Receptors, Chimeric Antigen, Retrospective Studies

DOI

10.3324/haematol.2021.280009

PMID

34758610

PMCID

PMC9244830

PubMedCentral® Posted Date

11-11-2021

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes