1185 Immunotherapy associated neurotoxicity, and potential re-challenge in select cases: a single center experience

<h3>Background</h3> Immune checkpoint inhibitors (ICI) associated neurotoxicity is a rare but serious immune-related adverse event (IrAE), and literature on immunotherapy (IO) re-challenge in these patients remains sparse. <h3>Methods</h3> We performed a single center retrospective study of patients who received ICI therapy between 2012-2024 at the University of Virginia Comprehensive Cancer Center, and developed neurotoxicity. We analyzed demographics, disease characteristics, treatments received, irAE details and management, comorbidities, treatment interruption, re-challenge rates and subsequent outcomes. <h3>Results</h3> 1979 patients received IO during this time for various indications. Of these, 23 patients developed ≥ grade(G)1 neurotoxicity. Median age was 64 years, 16 (70%) were male and 21 (91%) were white. Most frequent primary cancers were melanoma (43%), HCC (8.7%), Hodgkin Lymphoma (8.7%), RCC (8.7%)(table 1). Twelve (52%) patients received single agent IO, 8 (35%) received combination IO and 3 (13%) received chemotherapy plus IO (table 2). 57% of cases were peripheral neuropathies (table 4). Most common ≥G3 neurotoxicity was encephalitis with 7 cases (30%). Median number of IO infusions prior to neurotoxicity was 3 (IQR 2–5). Intent of therapy was palliative in 57%. Hospitalization was needed in 61% of cases. IO was interrupted in all patients, and was permanently discontinued in 17 patients (74%). Additional irAEs were noted in 14 patients (61%), concurrent in 7 patients (30%), prior in 5 patients (22%), subsequent in 4 patients (17%). A total of 6 patients (26%) resumed IO following a neurologic irAE, and two-thirds of those tolerated IO without further irAEs. However, 33% (n=2) of those who received IO re-challenge developed subsequent irAE - 1 case of recurrent neurotoxicity and one serious alternate irAE. Compared to patients treated with single agent immunotherapy, those who received combination immunotherapy tended to have more severe neurologic irAEs defined as ≥ G3 (88% vs 33%). They also tended have a higher proportion of progressive disease at first assessment after irAE (50% vs 30%)(table 3). Median overall survival and progression free survival (PFS) for entire cohort was 46.8 months and 7.6 months, respectively (figure 1). Median PFS was numerically better for patients re-treated with immunotherapy after neurotoxicity [3.7 months vs 26.2 months (HR 0.60, 95% CI 0.19–1.9), p=0.38]. <h3>Conclusions</h3> ICI can cause a broad spectrum of neurologic irAEs with life threatening complications. There was a trend towards improved PFS for those who received ICI re-challenge. ICI re-challenge after neurologic irAE is feasible in a select proportion of patients and needs careful evaluation on an individual basis.