ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicNovel Insights into CAR T-cell Associated Neurotoxicity - Volume IIView all articles
Early intrathecal dexamethasone and methotrexate as an effective approach for immune effector cell-associated neurotoxicity syndrome after CAR-T cell therapies
Provisionally accepted
- Tianjin First Central Hospital, Tianjin, China
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Introduction:Chimeric antigen receptor T (CAR-T) cell therapies have demonstrated remarkable success in treating relapsed and refractory (R/R) hematological malignancies. 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: Among the 13 patients, there were 7 cases of AML, 3 cases of ALL, 1 case of MM, 1 case of B-cell lymphoma, and 1 case of BPDCN, with a median age of 39 (11-65) years. The median number of prior lines of therapy was 7(1-16). There were 6 CAR-T products . The median CAR-T cell infusion dose was 2.0×106/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.
Keywords: car-t, immune effector cell-associated neurotoxicity syndrome (ICANS), Intrathecal dexamethasone and methotrexate, efficacy, safe
Received: 30 Sep 2025; Accepted: 03 Dec 2025.
Copyright: © 2025 Meng, Lv, Bai, Zhu, Pu, He, Xiao and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xiaoyuan He
Xia Xiao
Mingfeng Zhao
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