Late Adverse Events After Chimeric Antigen Receptor T-Cell Therapy for Patients With Aggressive B-Cell Non-Hodgkin Lymphoma.

in JAMA network open by Lina Camacho-Arteaga, Gloria Iacoboni, Mi Kwon, Rebeca Bailén, Rafael Hernani, Ana Benzaquén, Lucía López-Corral, Estefania Pérez-López, Lina María Leguízamo-Martínez, Maria Calvo-Orteu, Manuel Guerreiro, Aitana Balaguer-Rosello, Carla Alonso-Martínez, Xavier Vidal, Pere Barba, Antònia Agustí

TLDR

  • A cohort study of 172 adults with large B-cell lymphoma treated with CD19-targeted CAR T cells found that infections, neutropenia, and thrombocytopenia were common late adverse events, with nonrelapse-related mortality due to infections reported in some cases.

Abstract

Acute adverse events (AEs) after chimeric antigen receptor (CAR) T-cell infusion are well documented, but less information is available regarding the long-term toxic effects. To assess the occurrence of late AEs for adult patients with large B-cell lymphoma (LBCL) treated with commercially available CD19-targeted CAR T cells. A prospective, observational, clinical practice cohort study was conducted from September 1, 2018, to December 31, 2022, among 172 adult patients in 6 Spanish hospitals who received CD19-targeted CAR T-cell therapy for relapsed or refractory LBCL and survived at least 3 months after infusion, without subsequent antilymphoma therapy. Treatment with tisagenlecleucel or axicabtagene ciloleucel. Data on any late AEs occurring in this patient population were collected until the patients received new antilymphoma therapy, were lost to follow-up, died, or reached 24 months after infusion, whichever occurred first. Data collection for each patient started at the third month after infusion and included new-onset AEs, as well as persistent AEs that started earlier but were still ongoing at that time point. The study enrolled 172 patients (mean [SD] age, 58.5 [13.7] years; 101 men [58.7%]), of whom 135 (78.5%) experienced at least 1 late AE of any grade. Infections were the late AEs with the highest incidence (5.6 per 100 person-months [95% CI, 4.5-7.0 per 100 person-months]), followed by neutropenia (3.6 per 100 person-months [95% CI, 2.9-4.5 per 100 person-months]) and thrombocytopenia (2.2 per 100 person-months [95% CI, 1.7-3.0 per 100 person-months]). The incidence of infectious episodes remained stable during the whole study period, while cytopenias decreased beyond 6 months after infusion. All cases of nonrelapse-related mortality were due to infections (COVID-19 pneumonia in 3 patients and sepsis or bacterial pneumonia in 4 patients). Twenty-three patients (13.4%) experienced 27 dermatologic AEs, all mild, with most of them (88.9% [24 of 27]) starting beyond 3 months after infusion. Fifteen neurologic AEs were reported in 15 patients (8.7%), and 10 patients (5.8%) developed 13 cardiovascular AEs. Five secondary neoplasms were reported in 4 patients (2.3%), with no cases of T-cell malignant neoplasms. This cohort study suggests that CAR T-cell therapy has a favorable safety profile. However, continuous follow-up of patients is needed, as serious AEs can occur years after infusion.

Overview

  • The study aims to assess the occurrence of late adverse events (AEs) in adult patients with large B-cell lymphoma (LBCL) treated with commercially available CD19-targeted chimeric antigen receptor (CAR) T cells.
  • The study uses a prospective, observational, clinical practice cohort design to collect data on late AEs in 172 adult patients who received CD19-targeted CAR T-cell therapy for relapsed or refractory LBCL and survived at least 3 months after infusion.
  • The primary objective of the study is to investigate the incidence of late AEs in patients receiving CD19-targeted CAR T-cell therapy and to evaluate the safety profile of this treatment.

Comparative Analysis & Findings

  • The study found that infections were the most common late AE, with an incidence rate of 5.6 per 100 person-months, followed by neutropenia and thrombocytopenia.
  • The incidence of infectious episodes remained stable throughout the study period, while cytopenias decreased beyond 6 months after infusion.
  • The study also reported cases of nonrelapse-related mortality due to infections, which highlights the importance of monitoring patients for serious AEs after CAR T-cell therapy.

Implications and Future Directions

  • The study suggests that CAR T-cell therapy has a favorable safety profile, but continuous follow-up of patients is necessary to identify and manage late AEs.
  • Future studies should investigate the underlying causes of late AEs and explore strategies to prevent or mitigate their occurrence.
  • The study's findings also emphasize the importance of monitoring patients for serious AEs years after infusion, and highlight the need for long-term follow-up regimens.
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