Serious cardiovascular events rare after CAR T-cell therapy
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Key takeaways:
- Few patients experienced serious cardiovascular events after CAR T-cell therapy.
- The most common events included left ventricular dysfunction and supraventricular arrhythmia.
A meta-analysis of patients who underwent chimeric antigen receptor T-cell therapy for advanced blood cancers showed low prevalence of cardiovascular adverse events.
The two most common events — left ventricular dysfunction and supraventricular arrhythmia — occurred among less than 10% of patients.
“CAR T-cell therapies generally display relatively low cardiotoxic potential in adult populations with advanced hematologic malignant neoplasms,” David Koeckerling, MD, cardiology resident at University Hospital Heidelberg in Germany, and colleagues wrote.
Background and methods
CAR T-cell therapies are approved to treat multiple hematologic malignancies. However, the modality has been associated with adverse events, including cytokine release syndrome, neurotoxicity and hematotoxicity, according to study background.
“However, the cardiotoxic profile of CAR T-cell therapies remains poorly understood due to underrepresentation of patients with preexisting cardiovascular comorbidities in landmark clinical trials and the paucity of data generated in nontrial settings,” researchers wrote.
Koeckerling and colleagues aimed to assess the prevalence of adverse cardiovascular events among adults with advanced hematologic malignancies who underwent CAR T-cell therapy.
They searched the Embase, MEDLINE, Google Scholar and Cochrane Library databases to identify observational studies that included adults with advanced hematologic malignant neoplasms who underwent CAR-T and received systematic evaluation for cardiovascular complications.
The analysis included 13 studies that evaluated one of five CAR-T therapies: axicabtagene ciloleucel (Yescarta; Kite Pharma, Gilead Sciences), tisagenlecleucel (Kymriah, Novartis), lisocabtagene maraleucel (Breyanzi, Bristol Myers Squibb), brexucabtagene autoleucel (Tecartus, Kite Pharma/Gilead Sciences) or idecabtagene vicleucel (Abecma, Bristol Myers Squibb, 2seventy bio).
The studies also had to evaluate at least one of the following cardiovascular outcomes: cardiovascular death, ventricular arrhythmia, supraventricular arrhythmia, heart failure events, myocardial infarction or reduction in left ventricular ejection fraction.
The studies included a combined 1,528 patients (median age, 61 years; range, 58.7-63; 66% men). The majority (80%) had lymphoma, 85% had received prior anthracycline therapy, 27% had undergone stem cell transplantation and 17.5% received radiotherapy.
Prevalence of cardiovascular adverse events served as the primary outcome.
Results and next steps
After median follow-up of 487 days (range, 294-530), results showed a cardiovascular mortality rate of 0.63% (95% CI, 0.13-1.38).
Less than 1% of patients developed ventricular arrhythmia (0.66%; 95% CI, 0-2.28) or myocardial infarction (0.62%; 95% CI, 0.02-1.74).
The most prevalent cardiovascular adverse events included left ventricular dysfunction (8.68%; 95% CI, 2.26-17.97), supraventricular arrhythmia (7.79%; 95% CI, 4.87-11.27) and heart failure events (3.87%; 95% CI, 1.77-6.62).
Seven studies assessed all-cause mortality. A random-effects meta-analysis showed a pooled prevalence of all-cause mortality of 30.01% (95% CI, 19.49-41.68).
Researchers acknowledged study limitations, including the retrospective nature of most studies in the analysis, lack of pretreatment workups on patients, inconsistency in surveillance after CAR-T and the short duration of follow-up.
Prospective studies evaluating cardiovascular events for this population are needed, investigators wrote.
“Placing this study in the context of evolving immunotherapy technologies — such as bispecific T-cell effectors and off-the-shelf allogeneic CAR T-cell and CAR natural killer cell therapies — the recommendation of using prospective, multicenter, international registries for cardiovascular complications is an opportune one because the cardiometabolic and immuno-oncological paths show extensive connections that influence the immediate and potentially the long-term therapeutic outcomes,” Vlad G. Zaha, MD, PhD, MBA, associate professor in the department of internal medicine at UT Southwestern Medical Center, wrote in an accompanying editorial.
References:
- Koeckerling D, et al. JAMA Netw Open. 2024;doi:10.1001/jamanetworkopen.2024.37222.
- Zaha VG, et al. JAMA Netw Open. 2024;doI:10.1001/jamanetworkopen.2024.37157.
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