# Delayed fatal neurotoxicity in post CAR-T cell therapy for multiple myeloma, a case report

## TL;DR

A patient with multiple myeloma experienced fatal delayed neurotoxicity after CAR-T cell therapy, highlighting the need for long-term monitoring and new treatment approaches.

## Contribution

This case report presents a rare fatal outcome of delayed neurotoxicity following CAR-T therapy, emphasizing the importance of prolonged vigilance.

## Key findings

- A 61-year-old patient developed severe neurotoxicity 50 days after CAR-T therapy and died 93 days post-infusion.
- MRI showed T2/FLAIR hyperintensities in the basal ganglia and brainstem, with post-mortem findings of hippocampal sclerosis and gliosis.
- The case suggests a need for novel strategies to manage late-onset neurotoxicity in CAR-T therapy.

## Abstract

Anti-BCMA CAR T-cell therapy, specifically ciltacabtagene autoleucel, has significantly improved outcomes for relapsed/refractory multiple myeloma (RRMM). While early-onset immune-effector cell–associated neurotoxicity syndrome (ICANS) is a recognized complication, delayed-onset and non-ICANS neurological syndromes, such as movement and neurocognitive toxicity (MNT), present unique diagnostic and therapeutic challenges.

We report a case of a 61-year-old female with a 15-year history of RRMM who developed severe, delayed neurotoxicity 50 days after ciltacabtagene autoleucel infusion. The clinical course began with confusion and rapidly progressed to grade 4 ICANS characterized by lethargy, rigidity, and parkinsonian features. Serial MRI imaging revealed evolving, symmetric T2/FLAIR hyperintensities in the basal ganglia and brainstem, and reactive pachymeningitis. Despite aggressive multi modal immunosuppression, the patient’s condition remained refractory and expired on day 93. Post-mortem autopsy confirmed severe bilateral hippocampal sclerosis, diffuse gliosis, and microglial infiltration.

This case highlights a fatal presentation of delayed neurotoxicity that overlaps with the emerging MNT phenotype. As CAR-T therapies expand, this case underscores the necessity for prolonged clinical vigilance and the urgent need for novel management strategies for refractory, late-onset neurotoxicity.