Work

Early intrathecal dexamethasone and methotrexate as an effective approach for immune effector cell-associated neurotoxicity syndrome after CAR-T cell therapies

Year: 2025

Type: article

Abstract: Introduction: Chimeric antigen receptor T (CAR-T) cell therapies have demonstrated remarkable success in treating relapsed and refractory (R/R) B-cell hematological malignancies. Although the application of CAR-T therapy in acute myeloid leukemia (AML) is still restricted, we and other institutions have also demonstrated high complete remission rate of CAR-T targeting C-type lectin-like molecule 1 (CLL1) for R/R AML. However, CAR-T cell related toxicities such as steroid-refractory and severe immune effector cell-associated neurotoxicity syndrome (ICANS) can be life-threatening. Previous cases have reported potential efficacy of intrathecal corticosteroids alone or in combination with chemotherapy. Theoretically, intrathecal corticosteroids combined with intrathecal chemotherapy can control ICANS faster and better. Whether intrathecal dexamethasone and methotrexate (IDM) is beneficial for the patient with steroid-refractory or severe ICANS remains unclear. Methods: We retrospectively analyzed the clinical data of 13 patients with severe or steroid-refractory ICANS, and evaluated the effect of IDM in the treatment of severe ICANS or steroid-refractory ICANS by analyzing the changes in ICANS grade, ICE score, and laboratory indicators. Grade 3-4 ICANS downgraded to grade 1 and grade 1-2 ICANS recovery to an ICE score of 10 points is considered ICANS remission. Results: /kg. The median bone marrow blasts before lymphocyte depletion was 33.23%(5.34%-78.50%) and 9 patients had CNS involvement. All patients developed grade 1-2 CRS. Of the 13 patients, 5 had grade 3-4 ICANS and 8 had grade 1-2 ICANS. The median onset time of ICANS after CAR-T was 11(3-20) days. The median time of first IDM after ICANS was within 12 hours, and the median number of IDM was 1(1-3). The median time to ICANS remission was 1(1-7) days, with a response rate of 92.3% (12/13 patients). IDM significantly reduced CAR-T cells and tended to reduce protein and IL-6 levels in cerebrospinal fluid. As of June 30, 2025, the median OS and median PFS were 6 months and 5 months, respectively. Conclusion: Our data suggest that early administration of IDM may contribute to a rapid resolution of severe or steroid-refractory ICANS after CAR-T cell therapies, which may create opportunities for subsequent treatments in these patients. Larger sample and multicenter clinical trials are warranted to further validate these findings.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2025.1716317