Baseline PET-CT in predicting CRS and survival outcomes of R/R MM patients following CAR T-cell therapy

Abstract Background Patients with relapsed/refractory multiple myeloma (R/R MM) receiving chimeric antigen receptor (CAR) T-cell therapy are at high risk of toxicities, including cytokine release syndrome (CRS). The roles of positron emission-tomography computed tomography (PET-CT) in predicting these toxicities and outcomes remain unclear. Methods We retrospectively studied 62 patients with R/R MM who received B-cell maturation antigen (BCMA) CAR T-cell therapies at our center. Logistic regression analyses were employed to identify the predictive values of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) for severe CRS classified as grade 3 to 4. Additionally, Kaplan-Meier analyses and multivariate Cox regression analyses were performed to evaluate the predictive capability of MTV and TLG for survival outcomes of these patients. Results Baseline MTV of more than 107.2 cm3 and TLG exceeding 406.5 were classified as high MTV and high TLG, respectively. Both high MTV (P=0.008) and high TLG (P=0.011) were identified as independent risk factors for the development of severe CRS. Moreover, multivariate logistic regression analyses indicated that the administration of tocilizumab for the treatment of CRS was associated with high MTV (P=0.005) or high TLG (P=0.010). Similarly, the application of glucocorticoids was also related to high MTV (P=0.034) or high TLG (P=0.015). Additionally, patients with either low MTV (P=0.008) or low TLG (P=0.013) displayed superior progression-free survival (PFS) compared to those with high MTV or TLG. Notably, after a long-term follow-up period of 5.3 years, Kaplan-Meier analyses revealed that low TLG (P=0.034) but not low MTV (P=0.076) exhibited superior predictive capacity for long-term overall survival (OS). Nevertheless, our multivariate Cox models that incorporated either MTV (HR=2.144, 95% CI:1.019-4.521; P=0.044) or TLG (HR=2.544, 95% CI:1.203-5.380; P=0.015) along with high-risk cytogenetics demonstrated strong predictive capabilities for the long-term OS. Conclusions Baseline high MTV or TLG measured by PET-CT are recognized as adverse prognostic indicators for the incidence of severe CRS and poor survival outcomes in patients with R/R MM undergoing BCMA CAR T-cell therapy.