Product-dependent cardiac functional trajectories following CD19 CAR-T therapy 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
Cardiovascular toxicity is increasingly recognised after CD19 chimeric antigen receptor T-cell (CAR-T) therapy for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). However, whether different commercially available CD19 CAR-T products induce distinct patterns of subclinical myocardial dysfunction remains unclear.
Purpose
To prospectively define product-specific cardiac functional trajectories and biomarker responses following CD19 CAR-T therapy in patients with DLBCL.
Methods
We prospectively 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), global longitudinal strain (GLS), troponin T, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were assessed at baseline and on days 3, 7, 14 and 28 following infusion. Longitudinal changes were analysed using paired comparisons with baseline as reference, and product-by-time interactions were evaluated to compare temporal trajectories across products.
Results
The mean age was 63.2 years, and 32 patients (35%) were female. Distinct product-dependent cardiac trajectories were identified. Patients treated with tisagenlecleucel demonstrated a significant transient reduction in GLS (17.7±2.6% at baseline to 15.2±2.9% at day 14; p<0.001), followed by partial recovery by day 28. In contrast, patients treated with lisocabtagene maraleucel or axicabtagene ciloleucel showed no significant GLS changes at any time point. Patients treated with tisagenlecleucel (243±475 to 606±705 pg/mL; p<0.001) and lisocabtagene maraleucel (295±371 to 670±981 pg/mL; p=0.004) demonstrated early NT-proBNP elevation at day 3, whereas patients treated with axicabtagene ciloleucel showed a delayed and heterogeneous NT-proBNP response without significant early elevation. Across all treatment groups, LVEF remained preserved and troponin T did not significantly increase during follow-up.
Conclusions
CD19 CAR-T therapy demonstrates product-dependent differences in cardiac functional trajectories, characterised by transient impairment in GLS and distinct patterns of NT-proBNP elevation, without significant overall changes in LVEF. These findings indicate that cardiac responses following CAR-T therapy are not uniform across platforms and support the need for risk-adapted cardiac surveillance strategies.Cardiac Changes by CD19 CAR-T Product