Inflammatory Biomarkers and Outcomes in Multiple Myeloma Patients after CAR T-Cell Therapy

Introduction: CAR T-cell therapy is an effective tool for the treatment of multiple myeloma but produces a systemic inflammatory response which can manifest as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and other neurologic toxicities, and hyperferritinemia. Understanding the factors associated with these complications can help clinicians better evaluate their patients' candidacy for CAR T-cell therapy. In this study, we assessed whether baseline values of inflammatory biomarkers were associated with outcomes after CAR T-cell therapy. Methods: We retrospectively reviewed multiple myeloma patients who underwent CAR T-cell therapy with commercial products or on clinical trials at The Mount Sinai Hospital between 2017 and 2023. We gathered data on lab parameters that we felt were indicative of patients' baseline inflammatory status including C-reactive protein (CRP), ferritin, D-dimer, fibrinogen, absolute lymphocyte count (ALC), and absolute neutrophil count (ANC). Baseline data were collected prior to lymphodepletion. Outcomes of interest were occurrence and maximum grade of CRS and ICANS, occurrence of delayed neurotoxicity, attainment of peak ferritin ≥5000 within 30 days of infusion, progression-free survival (PFS), and overall survival (OS). Univariate logistic regression was used to assess the association between baseline labs and CRS, ICANS, delayed neurotoxicity, and peak ferritin ≥5000. Ordinal logistic regression was used to assess the baseline labs' association with maximum grade of CRS and ICANS, while proportional cox regression was used to assess their association with OS and PFS. The percentage of bone marrow plasma cells pre-CAR T, which we used as a surrogate for tumor burden, was included as a covariate on multivariable analyses. Results: A total of 101 patients treated with CAR T cells were included - 45 with ciltacabtagene autoleucel, 37 with idecabtagene vicleucel, and 19 with other products on clinical trials. Median age was 63 (range 37-82), median baseline marrow plasma cells percentage was 5% (range 0%-95%), and median follow-up was 11.9 months. Patients had a median (IQR) CRP of 4.0 mg/L (1.8, 11.8), ferritin of 174 ng/mL (68, 364), D-dimer of 0.6 mcg/L (0.4, 1.2), fibrinogen of 397.0 mg/dL (334.0, 477.5), ALC of 0.8 x10 3/µL (0.5, 1.1), and ANC of 2.7 x10 3/µL (1.9, 3.6). CRS occurred in 88.2% of patients (3.9% grade ≥3), ICANS in 15.7% (all grade