Prospective evaluation of cardiac function in relapsed/refractory multiple myeloma patients undergoing BCMA CAR-T therapy

Background Multiple myeloma (MM) is a plasma cell malignancy that, despite recent therapeutic advances, remains incurable. Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising treatment option for relapsed/refractory multiple myeloma (RRMM), resulting in high response rates. Previous studies in diffuse large B-cell lymphoma (DLBCL) have shown that cardiac dysfunction, possibly due to cytokine release syndrome (CRS), can occur after CAR-T therapy (1-6). We have previously reported prospective data on cardiac function after CAR-T therapy in DLBCL (7), but no prospective studies have yet examined changes in cardiac function after CAR-T therapy in MM. Objectives The aim of this study was to prospectively assess sequential changes in cardiac parameters in RRMM patients treated with anti-BCMA CAR-T therapy and to determine the relationship between CRS severity and cardiac dysfunction. Methods This prospective study enrolled 30 patients with RRMM treated with anti-BCMA CAR-T therapy. Cardiac biomarkers (NT-proBNP, troponin T) and echocardiographic parameters (left ventricular ejection fraction [LVEF], global longitudinal strain [LVGLS]) were sequentially assessed. Patients were divided into two groups according to CRS severity (low CRS: CRS <2, high CRS: CRS ≥2) and cardiac biomarkers and echocardiographic measurements were compared between these groups. Results The mean age of participants was 64.8 years, 14 (47%) were female; of the 30 patients, 20 (67%) were allocated to the low CRS group and 10 (33%) to the high CRS group. Tocilizumab was given to 18 patients in the low CRS group and to all 10 patients in the high CRS group. Cardiac parameters at baseline were not significantly different between the two groups. However, on days 3 and 7 after CAR-T treatment, the high-CRS group had significantly higher NT-proBNP levels than the low-CRS group (p = 0.033 and p = 0.023, respectively) (Fig. 1). In contrast, troponin T, LVEF and LVGLS did not show significant differences at any time point. Notably, among the high CRS group, one patient had a transient drop in LVEF of >30% on day 7, which improved on day 28, suggesting that this was a reversible event. Conclusions The first prospective assessment of cardiac function in MM patients treated with anti-BCMA CAR-T therapy showed a transient increase in NT-proBNP in the high CRS group, but no significant differences in troponin T, LVEF or LVGLS between groups; LVEF was markedly reduced but was reversible in one patient, but the overall findings indicated that cardiac dysfunction after CAR-T treatment in MM may be limited and mainly reversible. Further studies are needed to confirm the long-term clinical relevance of these findings.