Impact of autoimmune disease on toxicity and outcomes after idecabtagene vicleucel in patients with multiple myeloma.

Abstract

7552 Background: Idecabtagene vicleucel (ide-cel), an autologous BCMA-directed chimeric antigen receptor (CAR) T-cell therapy, has the potential to cure patients with relapsed/refractory multiple myeloma (RRMM). However, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are common treatment-related adverse events. Historically, patients with autoimmune disease (AD) have been excluded from CAR-T trials due to uncertain outcomes. This study evaluates differences in ICANS, relapse, and survival in RRMM patients with and without AD treated with ide-cel. Methods: A retrospective study of RRMM patients with AD treated with ide-cel at Moffitt Cancer Center in Tampa, FL between 2021-2024 was conducted. Clinically significant AD requiring medical management prior to apheresis included AIHA, autoimmune thyroiditis, ITP, RA, AIDP, CIDP, UC, SLE and PMR. T-tests and Kaplan-Meier estimates analyzed associations between AD, toxicities, and survival. Results: Of 179 patients with RRMM who received ide-cel, 13 (7%) had clinical AD with a median age of 72 years (range: 58 - 81 years, 54% female [n=7]). The incidence of ICANS was 23.1%, versus 23.6% for patients without AD (n = 166). The incidence (p = 1) and duration (p = 0.822) of ICANS was not significantly different in those with or without AD. Two patients (with AIHA and ITP) were tapered off of prednisone prior to ide-cel. Per medical records, the remaining patients were not on immunosuppressive medications for AD at treatment. All AD patients experienced CRS versus 85% of patients without AD (p = 0.225). For AD patients who experienced ICANS, median LDH (202 U/L vs 189 U/L, p = 0.061) and ferritin (528 ng/mL vs 284 ng/mL, p = 0.866) 5 days prior to infusion (day -5) was not significantly higher versus AD patients with no ICANS. However, median CRP at day -5 was significantly higher (1.2 mg/L vs 0.365 mg/L, p = 0.05). In AD patients who experienced ICANS, median LDH (872 U/L vs 268U/L, p = 0.01) and ferritin (10200 ng/ml vs 3000 ng/ml, p = 0.05) were significantly higher at the day of maximum grade ICANS versus patients without AD. However, there was no difference in median CRP (7.46 mg/L vs 7.72 mg/L, p = 0.9). Among patients who experienced ICANS, AD patients did not have significantly lower progression free survival (PFS) versus patients without AD at 30 days, 12 months, and 18 months (p = 0.07). There was no difference in overall survival between patients with or without AD. Conclusions: This retrospective study shows that pre-existing AD does not increase the risk of ICANS in patients with RRMM who were treated with ide-cel. Although LDH and ferritin levels were similar, levels of CRP were significantly higher in AD patients who experienced ICANS versus those that did not. Given notable differences in levels of inflammation and relapse rates among patients with AD, these patients may benefit from close monitoring.