Dataset Information

Adverse Cardiovascular and Pulmonary Events Associated With Chimeric Antigen Receptor T-Cell Therapy.

ABSTRACT:

Background

Pivotal trials of chimeric antigen receptor T-cell (CAR-T) have identified common toxicities but may have been underpowered to detect cardiovascular and pulmonary adverse events (CPAEs).

Objectives

This study sought to investigate CPAEs associated with commercial CD19-directed CAR-T therapy.

Methods

In this retrospective, pharmacovigilance study, the authors used the Food and Drug Administration adverse event reporting system to identify CPAEs associated with axicabtagene-ciloleucel and tisagenlecleucel. The authors evaluated disproportionate reporting by the reporting odds ratio (ROR) and the lower bound of the information component 95% credibility interval (IC₀₂₅ >0 is deemed significant). Significant associations were further adjusted to age and sex (adj.ROR).

Results

The authors identified CAR-T reports of 2,657 patients, including 546 CPAEs (20.5%). CPAEs overlapped with cytokine release syndrome in 68.3% (373 of 546) of the reports. Compared with the full database, CAR-T was associated with overreporting of tachyarrhythmias (n = 74 [2.8%], adj.ROR = 2.78 [95% CI: 2.21-3.51]), cardiomyopathy (n = 69 [2.6%], adj.ROR = 3.51 [2.42-5.09]), pleural disorders (n = 46 [1.7%], adj.ROR = 3.91 [2.92-5.23]), and pericardial diseases (n = 11 [0.4%], adj.ROR = 2.26 [1.25-4.09], all IC₀₂₅ >0). Venous thromboembolic events (VTEs) were associated only with axicabtagene-ciloleucel therapy (n = 28 [1.6%], adj.ROR = 1.80 [1.24-2.62], IC₀₂₅ >0). Atrial fibrillation (n = 55) was the leading tachyarrhythmia, followed by ventricular arrhythmias (n = 14). Tachyarrhythmias and VTEs were reported more often following axicabtagene-ciloleucel than tisagenlecleucel in an age- and sex-adjusted model (adj.ROR = 1.82 [1.04-3.18] and adj.ROR = 2.86 [1.18-6.93], respectively). Finally, the fatality rate of CPAEs was 30.9%.

Conclusions

In this largest post-marketing study to date, the authors identified an association between CAR-T and various CPAEs, including tachyarrhythmias, cardiomyopathy, pericardial and pleural disorders, and VTEs. These findings should be considered in the multidisciplinary assessment for and monitoring of CAR-T therapy recipients.

SUBMITTER: Goldman A

PROVIDER: S-EPMC8562317 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Adverse Cardiovascular and Pulmonary Events Associated With Chimeric Antigen Receptor T-Cell Therapy.

Goldman Adam A Maor Elad E Bomze David D Liu Jennifer E JE Herrmann Joerg J Fein Joshua J Steingart Richard M RM Mahmood Syed S SS Schaffer Wendy L WL Perales Miguel-Angel MA Shouval Roni R

Journal of the American College of Cardiology 20211101 18

<h4>Background</h4>Pivotal trials of chimeric antigen receptor T-cell (CAR-T) have identified common toxicities but may have been underpowered to detect cardiovascular and pulmonary adverse events (CPAEs).<h4>Objectives</h4>This study sought to investigate CPAEs associated with commercial CD19-directed CAR-T therapy.<h4>Methods</h4>In this retrospective, pharmacovigilance study, the authors used the Food and Drug Administration adverse event reporting system to identify CPAEs associated with axi ...[more]

PMID: 34711339

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Project description:ImportanceAcute 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.ObjectiveTo 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 participantsA 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.ExposureTreatment with tisagenlecleucel or axicabtagene ciloleucel.Main outcomes and measuresData 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.ResultsThe 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 relevanceThis 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.

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Dataset Information

Adverse Cardiovascular and Pulmonary Events Associated With Chimeric Antigen Receptor T-Cell Therapy.

Background

Objectives

Methods

Results

Conclusions

Publications

Adverse Cardiovascular and Pulmonary Events Associated With Chimeric Antigen Receptor T-Cell Therapy.

Similar Datasets

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