Haematologica (Nov 2021)

Cardiovascular events in patients treated with chimeric antigen receptor T-cell therapy for aggressive B-cell lymphoma

  • 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

DOI
https://doi.org/10.3324/haematol.2021.280009
Journal volume & issue
Vol. 107, no. 7

Abstract

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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.