Frontline therapy combining with intrathecal dexamethasone effectively alleviate immune effector cell-associated neurotoxicity syndrome in pediatric relapsed B-ALL receiving pCAR-19B-cases report

Abstract Background pCAR-19B is the first domestically approved CAR-T cell therapy for the treatment of children and adolescents targeting CD19. It has demonstrated efficacy and durability but is associated with significant side effects, particularly immune effector cell-associated neurotoxicity syndrome (ICANS). Currently, the frontline treatment for ICANS primarily involves intravenous corticosteroids and supportive care. However, some patients do not respond to this initial therapy, and there is a lack of treatment strategies for these non-responsive patients. Case presentation This case is registered on Clinicaltrials.gov under the number NCT05334823. Table 1 outlines the patient characteristics. Two patients achieved complete remission post CAR-T therapy. In Case 1, neurological symptoms began on the 6th day at grade 2 and progressed to grade 4 on the 8th day, accompanied by respiratory depression necessitating endotracheal intubation and ventilator-assisted ventilation due to cerebral edema. Case 2 experienced grade 3 ICANS on the 9th day, which quickly escalated to grade 4 the following day. Both patients were treated with frontline therapy, including antiseizure medications, steroid infusions, and intrathecal (IT) dexamethasone. Their ICANS gradually improved, and levels of temperature, IL-6, CRP, and PCT decreased progressively. For Case 1, steroid therapy lasted 10 days, after which ICANS returned to grade 2. The cumulative steroids administered reached 348 mg, but no significant effect on CAR copy number amplification was observed. For Case 2, steroid therapy lasted 3 days, and ICANS returned to grade 2 by the 3rd day post-steroid treatment. The cumulative steroid dose was 22.9 mg, with no impact on CAR amplification. Both patients are currently alive following bone marrow remission bridging. Their progression-free survival (PFS) was 150 days for Case 1 and 290 days for Case 2. As of October 1, 2023, their overall survival (OS) was 234 days for Case 1 and 305 days for Case 2. Conclusions A preliminary analysis suggests that the combination of frontline therapy and intrathecal dexamethasone is feasible, safe, and effective in these two patients receiving pCAR-19B for relapsed B-ALL. This approach may enhance the safety profile of pCAR-19B administration and broaden access to this treatment.