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
Fridberg et al. (Thu,) studied this question.