Tandem Meetings 2026 | Comparing the cardiovascular safety of approved CAR-T products for LBCL

The CARTiAC project is basically an international retrospective study that spanned across six tertiary centers, three different countries, looking at the cardiac complication landscape following the CD19 CAR-T therapy for large B-cell lymphoma. The published reports thus far indicate that the cardiac complications that happened in the context of CD19 CAR-T therapy ranged between 5% to 15%. However, most of the published reports do not address the particular cardiac complication per CAR-T products, and it does not compare the CAR-T products among each other with regards to the cardiac safety post-administration of these products. And the primary goal of this study is to first provide a large descriptive analysis of the cardiac complication landscape post-CAR-T and then compare different CAR-T products and establish the differences between them and if there is any distinct signal with regards to the safety and toxicity. And eventually reaching to establishing differences in product selection for patients, particularly patients with significant cardiovascular disease or at higher risk of having cardiovascular disease post-CAR T-cells. 

So the study included more than 900 patients distributed among the three FDA-approved CD19 CAR-T products for lymphoma. Most patients received axi-cel, and the second most common was liso-cel and then followed by tisa-cel. And the incidence of cardiovascular comorbidities or cardiovascular risk factors in the included patients was very high. So about at least half of the included patients have one or two cardiovascular risk factors coming into CD19 CAR-T therapy, and about one in five patients or almost 20% have more than three or more cardiovascular risk factors. Indicative of the real-world nature of this study and indicative of the patients that we see every day who are usually slightly older and have usually one or two cardiovascular risk factors. 

The incidence of cardiovascular complications between the start of fludarabine for depletion on day minus 5 and day 30 post CAR-T treatment was 9% in our study. We observed a slight increase in the cardiovascular complications in the tisa-cel compared to other products at more than 25% in the tisa-cel compared to other products. However, we also observed differences in the type of CV events that happen after each product. The most common cardiovascular complication was atrial arrhythmias, manifested by atrial flutters and atrial fibrillation. Supraventricular tachycardia was the second most common. And interestingly enough, we also saw differences in the median time to the first cardiovascular events among different CAR-T products. For example, while the tisa-cel was the earliest median time to the first cardiovascular events was five days post-infusion, the latest median time to first cardiovascular events in the liso-cel cohorts was up to nine days post-infusion. We also observed that the axi-cel and the tisa-cel cohorts cardiovascular events cluster early post-infusion in the first week and follows an early peak and then kind of slow down after that, while the liso-cel follows a more peakless, flat pattern of cardiovascular complication that goes all the way up to the one month after the CAR-T infusion. 

And finally, since this is a large group of patients who are heterogeneous in their characteristics, we performed a propensity score matching analysis in which we matched patients together to decrease the heterogeneity of these cohorts. And we adjusted for, we identified multiple covariates that we adjusted for in the propensity score matching analyses that include age, functional status, tumor burden, and the number of pre-CAR-T cardiovascular risk factors that we talked about in the beginning. And then we compared the cardiovascular safety of each CAR-T product using the propensity score matched analyses. The first one was comparing axi-cel to tisa-cel. Tisa-cel was associated with a higher cardiovascular complication within the first 30 days post CAR-T infusion compared to the Axicabtagene ciloleucel in an adjusted logistic regression model and also in propensity score matching analyses. And the second comparison was between axi-cel and liso-cel. And in that part, liso-cel was associated with lower cardiovascular complication, post-CAR-T infusion within the first 30 days in an adjusted logistic regression model, also in propensity score matching analysis. 

And the last thing, we looked at the overall survival of patients who developed cardiovascular complications in the first 30 days post-CAR T-cells to those who did not develop cardiovascular complications. And the overall survival was lower in the group who developed cardiovascular events, highlighting the significance of this complication and the impact overall on the outcome, with about 10% difference of overall survival by the end of first year. And this overall survival signal was mostly driven by an increase in non-relapse mortality. Despite that was not statistically significant in our cohorts, the patients who developed cardiac events within the first 30 days post-CAR T-cells demonstrated an increase in non-relapse mortality by the end of first year. 

I think the conclusion of this study is that many of our patients that we treat have significant cardiovascular comorbidities and particular attention should be paid to optimizing the cardiac safety of this group of patients, and involving and engaging the cardiovascular expert in that regard is important to mitigate the toxicity. And then our data suggests that, results suggest that it may actually inform product selection in a sense of patients with cardiovascular, pre-existing cardiovascular disease, or patients with a significant higher risk of developing cardiovascular post-CAR T-cells, liso-cel appears to be safer compared to axi-cel.

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