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

Abstract

IMPORTANCE 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. OBJECTIVE 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. DESIGN, SETTING, AND PARTICIPANTS 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. EXPOSURE Treatment with tisagenlecleucel or axicabtagene ciloleucel. MAIN OUTCOMES AND MEASURES 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. RESULTS 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. CONCLUSIONS AND RELEVANCE 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.