What question did this study set out to answer?

The study aims to develop a standardized protocol to mitigate ICANS in high-risk elderly patients treated with CD28-based CAR-T cells.

February 14, 2026Open Access

ICANS mitigation in high-risk elderly patients treated with CD28 co-stimulatory anti-CD19 CAR-T cells using a standardization protocol: a pilot study

Key Points

The study aims to develop a standardized protocol to mitigate ICANS in high-risk elderly patients treated with CD28-based CAR-T cells.
Single-arm prospective pilot study
Participants aged ≥75 years or ≥65 years with additional risk factors
Standardized protocol includes levetiracetam, thiamine, corticosteroids, and anakinra for ICANS
Endpoints measured were ICANS duration, refractoriness, and response.
67% of patients experienced grade ≥3 ICANS, with a median ICANS duration of 4 days
31% experienced refractory ICANS
No patient characteristics reliably predicted ICANS metrics except for LDH showing a trend
Cumulative steroid use was correlated with infections and non-relapse mortality.

Abstract

CAR-T has transformed relapsed/refractory LBCL treatment, with CD28-based products yielding rapid responses but higher ICANS rates. With Axicabtagene-ciloleucel and Brexucabtagene-autoleucel, overall and severe ICANS reach 78% and 35%, respectively. Older adults are vulnerable, yet mitigation strategies remain lacking. We aimed to develop and implement a standardized ICANS mitigation protocol for older adults receiving CD28- based anti-CD19 CAR-T, addressing this critical gap. We conducted a single-arm prospective pilot study in patients ≥75yr or ≥65 with additional risk factor receiving CD28-based CAR-T. The protocol included levetiracetam and thiamine prophylaxis, early grade-based corticosteroids and anakinra for grade ≥3 and refractory ICANS – defined as no improvement within 24hr. Endpoints were ICANS duration, refractoriness, response and toxicity. Forty-five patients met eligibility; median age 75 (65-86), 78% had ECOG ≥2 and 42% with neurologic comorbidity. Overall, grade ≥3, and refractory ICANS developed in 67%, 31%, and 20%, respectively. Median ICANS duration was 4 days, shorter than previous cohorts. Disease and patients’ characteristics did not predict ICANS metrics, excluding LDH showing trend for severe ICANS (p=0.07). mEASIX and ICANS-PSS scores were not predictive; expansion was not compromised. Cumulative steroids associated with infections (p=.002) and NRM (p

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