Product-specific longitudinal cardiac functional and biomarker responses after CD19 CAR-T y in diffuse large B-cell lymphoma
I Sunayama, K D Min, Y Orihara, M Oboshi, S Yoshihara, K Yoshihara, H Tamaki, M Asakura, M IshiharaAbstract
Background
Chimeric antigen receptor T-cell (CAR-T) therapy is an established treatment for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Although cardiovascular toxicity following CAR-T therapy has been reported, whether longitudinal cardiac functional and biomarker responses differ among commercially available CD19 CAR-T products remains incompletely understood.
Purpose
To prospectively evaluate temporal changes in cardiac function and biomarkers following CAR-T therapy in DLBCL and to compare cardiac response profiles among three commercial CD19 CAR-T products (tisagenlecleucel, lisocabtagene maraleucel, and axicabtagene ciloleucel).
Methods
This prospective observational study enrolled 91 consecutive patients with DLBCL undergoing CD19-directed CAR-T therapy (tisagenlecleucel n=33, lisocabtagene maraleucel n=34, axicabtagene ciloleucel n=24). Left ventricular ejection fraction (LVEF), left ventricular global longitudinal strain (LVGLS), and serum biomarkers (troponin T and NT-proBNP) were assessed at baseline and on days 3, 7, 14, and 28 after CAR-T infusion. Longitudinal changes within each product were evaluated using paired comparisons with baseline as reference.
Results
The mean age was 63.2 years, and 32 patients (35%) were female. Distinct product-specific longitudinal cardiac phenotypes were observed. Patients treated with tisagenlecleucel exhibited a significant transient impairment in myocardial deformation, with LVGLS declining from baseline (17.7±2.6%) to day 7 (16.4±3.5%, p=0.02) and reaching a nadir at day 14 (15.2±2.9%, p<0.001), followed by partial recovery by day 28. In contrast, no significant LVGLS changes were observed in patients treated with lisocabtagene maraleucel or axicabtagene ciloleucel at any time point. NT-proBNP demonstrated divergent temporal response patterns across products. Significant early NT-proBNP elevation at day 3 was observed in patients receiving tisagenlecleucel (243±475 to 606±705 pg/mL, p<0.001) and lisocabtagene maraleucel (295±371 to 670±981 pg/mL, p=0.004), whereas patients treated with axicabtagene ciloleucelshowed a delayed and heterogeneous NT-proBNP response without statistically significant early elevation. Across all products, LVEF remained preserved, and troponin T did not show a significant rise throughout follow-up.
Conclusions
CD19 CAR-T therapy is associated with distinct product-specific longitudinal cardiac phenotypes. Tisagenlecleucel shows greater transient LVGLS impairment with early NT-proBNP elevation, whereas lisocabtagene maraleucel and axicabtagene ciloleucel demonstrate milder or delayed biomarker responses. Product-specific cardiac monitoring may improve cardio-oncology surveillance.Cardiac Changes by CD19 CAR-T Product