Tumor Inflammation-Associated Neurotoxicity Masquerading as Severe Immune Effector Cell-Associated Neurotoxicity...

Tarlatamab, a delta-like ligand 3-targeting bispecific T-cell engager, has demonstrated promising efficacy in relapsed SCLC. Data on immune effector cell-associated neurotoxicity syndrome (ICANS) in patients with central nervous system disease remain limited. In particular, tumor inflammation-associated neurotoxicity (TIAN), proposed in chimeric antigen receptor T-cell therapy as localized neurotoxicity linked to peritumoral inflammation, has not been characterized in this setting.

Here, we describe a single case of severe neurotoxicity in a young woman with SCLC and multiple brain metastases who had a history of symptomatic epilepsy and received tarlatamab as fourth-line therapy. She developed sudden loss of consciousness (immune effector cell-associated encephalopathy score: 0) and seizures 27 hours after the initial 1 mg dose of tarlatamab. The patient's presentation met the criteria for grade 4 neurotoxicity. Brain imaging revealed enlarged brain metastases with worsened peritumoral edema, and electroencephalography demonstrated focal epileptiform discharges at the tumor site. The symptoms resolved rapidly (within 36 h) after intensified corticosteroid therapy. Tarlatamab was cautiously continued without recurrence of severe neurotoxicity, and subsequent imaging revealed marked tumor regression. The event was interpreted as TIAN driven by local tumor inflammation rather than ICANS.

Severe acute neurotoxicity may indicate TIAN in patients with SCLC and brain metastases treated with tarlatamab. TIAN presents as severe but reversible symptoms that mimic high-grade ICANS. Differentiating TIAN from ICANS is crucial because TIAN may be manageable, and its recognition may inform individualized decisions regarding therapy continuation under careful monitoring.