CAR-T, baseline risk factors confer elevated rate of major adverse CV events
Click Here to Manage Email Alerts
Patients who were treated with chimeric antigen receptor T-cell therapy had increased risk for major adverse CV events, researchers found.
Elevated baseline creatinine and grade 3 or 4 cytokine release syndrome were risk factors for events that included HF, nonfatal ACS, nonfatal ischemic stroke, new arrhythmias and CV death.
“Our study demonstrates that adults treated with CAR T-cell therapy have a high rate of cardiac events, in particular HF and atrial fibrillation,” Marielle Scherrer-Crosbie, MD, PhD, professor of medicine and director of the cardiac ultrasound laboratory at the Hospital of the University of Pennsylvania, told Healio. “As CAR T-cell therapy use increases, it is crucial to understand the possible side effects and time frame in which they can occur. Understanding the incidence and the natural history of CAR T-induced side effects can allow for better screening and follow-up for these patients.”
In a study published in JACC: CardioOncology, researchers determined the incidence of major CV events among 145 adults (median age, 60 years; 74% men; 9% with diabetes) treated with CAR T-cell therapy for hematologic malignancies.
Participants who underwent CAR T-cell therapy had received a diagnosis of acute lymphoblastic leukemia, chronic lymphoblastic leukemia or diffuse large B-cell lymphoma.
Researchers observed 176 instances of cytokine release syndrome among 104 patients within a median time to 6 days. A multivariable analysis showed that patients with cytokine release syndrome of grade 3 (HR = 8.42; 95% CI, 3.48-20.4) or grade 4 (HR = 29.86; 95% CI, 9.8-90.94) experienced significantly greater risk for major adverse CV events compared with those who did not.
The multivariable analysis also showed patients with elevated creatinine levels before CAR T-cell therapy were also at greater risk for adverse events (HR = 15.54; 95% CI, 3.67-65.86) compared with patients with normal levels.
Moreover, in a univariate analysis, participants who were taking aspirin (HR = 3.13; 95% CI, 1.09-8.99), statins (HR = 2.29; 95% CI, 1.11-4.73) or insulin (HR = 5.7; 95% CI, 1.7-19.08) had greater risk for major adverse CV events compared with patients who were not prescribed them.
“To our knowledge, this is the largest retrospective study conducted in adult patients treated with CAR T-cell therapy evaluating the occurrence of and risk factors associated with adverse cardiovascular events,” Bénédicte Lefebvre, MD, cardiologist at the Hospital of the University of Pennsylvania, and colleagues wrote. “We determined that baseline creatinine and grade 3 or 4 [cytokine release syndrome] were independently associated with [major adverse CV events]. CAR T-cell therapy has opened a new field in the treatment of hematologic malignancies and is now under investigation for other indications, including solid tumors.”
Other measures of risk
In other findings, researchers identified several clinical, laboratory and echocardiographic parameters with greater prevalence among patients who received CAR T-cell therapy and experienced major adverse CV events:
- prior atrial fibrillation (HR = 2.83; 95% CI, 1.08-7.43);
- elevated diastolic BP (HR for each 1 mm Hg increase = 0.95; 95% CI, 0.91-0.99);
- elevated hemoglobin (HR for each 1 g/dL increase = 0.83; 95%CI, 0.69-0.99); and
- platelet count (HR for each 1,000/µL increase = 0.99; 95% CI, 0.99-1).
“As CAR T-cell therapy use becomes more available and accessible, it is crucial to understand not only the benefits but the possible side effects and the time frame in which they can occur,” the researchers wrote. “In contrast to radiation or other potentially cardiotoxic chemotherapies, no guidelines are currently available for screening or surveillance of cardiac function of patients treated with CAR T-cell infusion. Understanding the incidence and the natural history of treatment-induced side effects will allow better screening and follow-up for these patients. To this effect, an extensive monitoring program in the United Kingdom is underway.”
The next step
“Ultimately, prospective data with systematic cardiac monitoring (imaging and inflammatory and cardiac biomarkers) is the next step in helping to understand the frequency and pathophysiology of CAR T-cell therapy-related CV adverse events,” Anna B. Catino, MD, of the division of cardiovascular medicine in the department of medicine at the University of Utah, Salt Lake City, wrote in a related editorial. “This study is an excellent report of the founding institution’s experience and demonstrates the high rate of [cytokine release syndrome]-associated CAR T-cell therapy and its clear association with CV toxicity. Because the predominant associated adverse CV effect appears to be HF, CAR T-cell therapy and [cytokine release syndrome], in turn, may offer further insight to a greater understanding of HF, myocardial injury and cardiac recovery.”
Reference:
Collapse
Click Here to Manage Email Alerts