Clinical characterization and outcome of 47 patients with neurologic adverse events of immune-checkpoint inhibitors (P4-5.026)

Abstract

<h3>Objective:</h3> To report the clinical spectrum, treatment, and outcome of a case series of neurologic iAEs. <h3>Background:</h3> Cancer treatment with immune checkpoint inhibitors (ICI) can associate with immune-related adverse events (iAEs) which can be life-threatening. <h3>Design/Methods:</h3> Retrospective assessment of patients with neurologic iAEs whose serum or CSF samples were studied in our laboratory (Jan2018–Sep2022). Clinical information was obtained through a structured questionnaire. Exclusion criteria were lack of clinical information and evidence of other causes of neurologic dysfunction. Treatment response was assessed within one month of symptom onset, and outcome at last follow-up visit. <h3>Results:</h3> 47 patients (29 males, 62%), median age 67 years (IQR60–74) were included. The most frequent tumors were lung cancer (28, 60%) and melanoma (9, 19%). 26 (55%) patients received anti-PD1, 13 (28%) PDL-1, and 8 (17%) both. Median time to neurologic iAEs was 15 weeks (IQR3–32). The initial presentations were: encephalopathy (30 patients, 64%), muscle weakness (9, 19%), ataxia (3, 6%), visual dysfunction (3, 6%), and constipation (2, 4%). Median mRS at nadir was 4 (3–5), and 7 (15%) patients required ICU. Abs were detected in 10 (21%; Ma2=3, Hu=2, GFAP=2, GABAbR=1, GAD65=1, AQP4=1). 42 (89%) were treated; all received steroids, 17 (36%) intravenous immunoglobulins, and 9 (21%) other immunosuppressants. Patients without early neurologic improvement (14, 30%) were more likely to be older, have lung cancer (p=0.01), and higher mRS at nadir (p=0.001) than those who improved. After a median follow-up of 107 days (45–356), mRS was 3 (0–6), and 26 (55%) patients had a poor outcome: 23 (49%) died (10 [21%] related to neurologic iAE) and the other 3 didn’t improve or worsened. Good outcome was associated with early neurologic improvement (p=0.001). <h3>Conclusions:</h3> In this case series with predominant CNS iAEs, half of the patients had poor clinical outcome, and in 20% the neurologic iAE was the cause of death. <b>Disclosure:</b> Elianet Fonseca has nothing to disclose. Mr. Cabrera Maqueda has nothing to disclose. Raquel Ruiz-Garcia has nothing to disclose. Dr. Naranjo Rondan has nothing to disclose. Dr. Blanco Morgado has nothing to disclose. Dr. Dalmau has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas Research Institute of America. Dr. Dalmau has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen Research &amp; Development . Dr. Dalmau has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Academy of Neurology. An immediate family member of Dr. Dalmau has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Dalmau has received research support from Sage Therapeutics. The institution of Dr. Dalmau has received research support from Edmond J.Safra Foundation . The institution of Dr. Dalmau has received research support from La Caixa Foundation. The institution of Dr. Dalmau has received research support from Spanish Ministry of Health (ISCIII). The institution of Dr. Dalmau has received research support from Euroimmun, Inc. Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care. Dr. Graus has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for MedLink. Dr. Graus has received intellectual property interests from a discovery or technology relating to health care. The institution of Dr. Martinez-Hernandez has received research support from Instituto de Salud Carlos III. Dr. Martinez-Hernandez has received personal compensation in the range of $0-$499 for serving as a travel and speaking honoraria with Biogen. Dr. Martinez-Hernandez has received personal compensation in the range of $0-$499 for serving as a travel honoraria with UCB.