Aggressive management may lead to fewer cardiac events after CAR T-cell therapy
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Key takeaways:
- Researchers found the rate of major adverse cardiovascular events after CAR-T to be lower than 5%.
- Major adverse cardiac events occurred in patients with cytokine release syndrome within 7 days of therapy.
Adults undergoing chimeric antigen receptor T-cell therapy are at low risk for major adverse cardiovascular events, according to data published in JACC: CardioOncology.
High occurrence of such events in prior retrospective studies indicated early intervention, aggressive treatment and close follow-up during cytokine release syndrome events as essential, according to researchers.
“CAR T-cell therapy appears safer than what was previously described, even as the prevalence of cardiovascular risk factors and diseases in our study was higher than in the general population,” Bénédicte Lefebvre, MD, assistant professor of clinical medicine in the department of medicine at Hospital of the University of Pennsylvania, told Healio.
“We believe that as the body of evidence [grows] and our understanding of CRS is more complete, treating sooner and more aggressively CRS events can possibly prevent future [major adverse cardiovascular events],” she added. “This is reassuring, as CAR T-cell therapy is being investigated for other types of cancers.”
Background and methodology
Previous retrospective studies have indicated that CAR-T could be associated with major adverse cardiovascular events (MACE), especially with regard to CRS events.
Therefore, researchers conducted a prospective observational study to define the occurrence of MACE in adults undergoing treatment with CAR-T to identify associated risk factors.
Researchers collected vital signs, blood samples and an echocardiogram prior to CAR-T infusion, as well as 2 days, 1 week, 1 month and 6 months after CAR-T infusion, with additional follow-up at 12 months.
In the event of CRS, health care professionals performed echocardiography within 72 hours.
Researchers defined MACE as cardiovascular death, symptomatic heart failure, acute coronary syndrome, ischemic stroke and newly diagnosed cardiac arrhythmia.
Study participants (n = 44; mean age 58 years; 77% men) had either lymphoma (n = 43 patients) or acute lymphoblastic leukemia (n = 1) and had a mean follow-up duration of 487 days (Q1-Q3: 258-622 days).
Results
Researchers noted 24 episodes of CRS in 23 patients (52%; 13 grade 1 events, 10 grade 2 events and one grade 3 event), with a median time to CRS of 4 days.
Meanwhile, two patients had a MACE following CAR-T infusion, including one patient who experienced heart failure with preserved ejection fraction 6 days after infusion and another who had atrial fibrillation 7 days after infusion.
Researchers noted no change in left ventricular ejection fraction but did observe a modest decrease in global longitudinal strain.
Next steps
Researchers observed a MACE incidence rate of less than 5%, with both events reported in patients with CRS occurring within 7 days of therapy. Prior studies alluded to potentially higher rates for CRS among those receiving CAR T cells; however, researchers stated that patients may have been less sick in this study due to receiving infusions sooner in their oncologic care plan that patients in prior studies, making them less likely to develop CRS.
More aggressive treatment can help mitigate cardiac complications, but more studies with larger patient pools are needed to better understand the potential risks, according to Lefebvre.
“We were surprised, yet relieved that the incidence of MACE and CRS were lower in this contemporary prospective study compared with our earliest work,” Lefebvre told Healio. “As a cardio-oncologist, in my higher risk patients receiving CAR-T, I will advise to treat aggressively and early these CRS events to avoid cardiac complications.”
A relatively small sample size served as a study limitation, Lefebvre said.
“Larger sample studies are needed to fully define the risks. It would also be interesting to follow patients with cardiac dysfunction (heart failure) undergoing CAR T-cell therapy,” she added. “Also, the long-term cardiac effects of CAR T cells are not well known, although we are not really expecting any based on previous work.”
For more information:
Bénédicte Lefebvre, MD, can be reached at the Department of Medicine, Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104, USA; email: benedicte.lefebvre@pennmedicine.upenn.edu.
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