Early Intrathecal Therapy for High-Grade ICANS in Patients Receiving CAR T-Cell Therapy

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In a single-institution retrospective review reported in JAMA Oncology, Zurko et al found that early intrathecal therapy with hydrocortisone with or without intrathecal chemotherapy was effective in treating grade ≥ 3 immune effector cell–associated neurotoxicity syndrome (ICANS) in patients receiving chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory B-cell non-Hodgkin lymphoma.

Study Details

The analysis included 74 patients receiving commercial anti-CD19 CAR T cells or bispecific lentiviral anti-CD19 and anti-CD20 CAR T cells between 2018 and 2021. Of 74 patients, 15 (20.3%) developed grade ≥ 3 ICANS.

Key Findings

Seven patients with steroid-refractory ICANS received intrathecal therapy (including chemotherapy in four) within 5 days of developing high-grade ICANS. CAR T cells were detected in each of six cerebrospinal fluid specimens tested. Three patients also received anakinra.

The results of this case series suggest that early intrathecal therapy is feasible and has clinical efficacy in the management of high-grade ICANS.
— Zurko et al

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All patients recovered from ICANS. The median cumulative corticosteroid dose was 713 mg (range = 446–914 mg) of dexamethasone-equivalents, and the median duration of corticosteroid use was 35 days (range = 22–43 days). Improvement to grade 1 ICANS occurred at a median of 6 days (range = 1–15) after development of high-grade ICANS and at a median of 2 days (range = 1–11 days) after intrathecal therapy. Estimated 1-year progression-free and overall survival was 57.1%, with a median follow-up of 611 days (range = 184–953 days) from CAR T-cell infusion among surviving patients. All surviving patients remained in complete remission at last follow-up. All patients who received anakinra died from infectious complications.

Seven patients did not receive intrathecal therapy and one received late intrathecal hydrocortisone 24 days after developing ICANS; of these patients, four had steroid-refractory ICANS. Estimated 1-year progression-free and overall survival was 18.8% among all eight patients and 0% for those with steroid-refractory ICANS. Two patients with non­–steroid refractory ICANS were alive and remained in complete remission at last follow-up (308 and 580 days). Three patients with steroid-refractory ICANS received additional treatment, consisting of cyclophosphamide in two and anakinra in one. The four patients with steroid-refractory ICANS had a median of 50 days (range = 23–62 days) of corticosteroid use and received a median cumulative dose of 962.5 mg (range = 876–1,083 mg) of dexamethasone-equivalents, both greater (P = .01) than among patients who received intrathecal therapy. Among these four patients, ICANS did not resolve in two and improved to grade 1 after 13 and 22 days in the remaining two, respectively.

The investigators concluded, “The results of this case series suggest that early intrathecal therapy is feasible and has clinical efficacy in the management of high-grade ICANS. For patients with steroid-refractory ICANS in this study, the duration and cumulative dose of corticosteroids was lower, the time to recovery to grade 1 ICANS was shorter, and progression-free and overall survival were greater among patients who received early intrathecal treatment. This data set is limited by the heterogeneity of the patients, disease, and ICANS treatments. However, our findings suggest there is a correlation among early intrathecal treatment and improved clinical outcomes.”

Nirav N. Shah, MD, MS, of the Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, is the corresponding author for the JAMA Oncology article.

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