Prospective evaluation of cardiac function following anti-BCMA CAR-T therapy in multiple myeloma

Background Multiple myeloma (MM) is a plasma cell malignancy that remains incurable despite recent therapeutic advancements. Anti–B-cell maturation antigen (BCMA) chimeric antigen receptor T cell (CAR-T) therapy has emerged as a promising approach for relapsed/refractory MM (RRMM), demonstrating high response rates. Previous studies of CAR-T therapy in diffuse large B-cell lymphoma (DLBCL) have shown that cardiac dysfunction, potentially mediated by cytokine release syndrome (CRS), can occur after treatment (1-6). We previously reported prospective data on cardiac function after CAR-T therapy in DLBCL (7). However, no prospective study has evaluated changes in cardiac function following CAR-T therapy in MM. Objectives To prospectively investigate the sequential changes in cardiac markers and clarify the relationship between CRS severity and adverse cardiac manifestations in RRMM patients treated with anti-BCMA CAR-T therapy. Methods In this prospective study, 30 patients with RRMM who underwent anti-BCMA CAR-T therapy were enrolled. Cardiac biomarkers (NT-proBNP, troponin T) and echocardiographic parameters (left ventricular ejection fraction [LVEF] and global longitudinal strain [LVGLS]) were sequentially collected. Patients were classified into two groups based on the severity of CRS (low-CRS group: CRS < 2; high-CRS group: CRS ≥ 2). Cardiac biomarkers and echocardiographic parameters were compared between the two groups. Results The average age of participants was 64.8 years, and 14 (47%) were female. Of the 30 patients, 20 (67%) were in the low-CRS group and 10 (33%) were in the high-CRS group. Tocilizumab was administered to 18 patients in the low-CRS group and all 10 patients in the high-CRS group. At baseline, there were no significant differences in cardiac parameters between the two groups. On days 3 and 7 after CAR-T therapy, the high-CRS group exhibited significantly higher NT-proBNP levels compared to the low-CRS group (p = 0.033 and p = 0.023, respectively) (Figure 1). In contrast, troponin T, LVEF, and LVGLS did not differ significantly between the groups at any time point. Within the high-CRS group, one patient experienced a transient LVEF decline of more than 30% on day 7, which returned to baseline by day 28, suggesting a reversible process. Conclusions In this first prospective investigation of cardiac function in MM patients undergoing anti-BCMA CAR-T therapy, transient elevations in NT-proBNP were observed in the high-CRS group, whereas significant alterations in troponin T, LVEF, and LVGLS were not detected between the two groups. Although one patient exhibited a notable but transient decline in LVEF, these findings suggest that overall cardiac dysfunction post–CAR-T therapy in MM may be limited and largely reversible, warranting further studies to confirm the long-term clinical significance of these observations.