Abstract Details

Title Clinical, Instrumental, and Prognostic Definitions of de novo Central Nervous System Demyelinating Disorders Following Immune Checkpoint Inhibitor Therapy

Topic Autoimmune Neurology

Presentation(s) P6 - Poster Session 6 (5:00 PM-6:00 PM)

Poster/Presentation
Number 2-001

Objective We aimed to define the demographic, clinical, therapeutic and prognostic features of DEMirAEs.

Background Immune-related adverse events (irAEs) can occur after the administration of immune-checkpoint inhibitors (ICI). De novo demyelinating irAEs (DEMirAEs) are rare, poorly characterized and often challenging.

Design/Methods We conducted a multicentric retrospective study including patients with DEMirAEs consecutively seen from 2011 to 2024 in 9 neurology units in Europe. Additional cases were identified by a systematic literature review (PRISMA guidelines). Patients with a known multiple sclerosis diagnosis at ICI initiation, and patients with typical MS lesions on first brain MRI after symptoms onset were excluded. All statistical analysis were performed using Stata/SE and R version 4.0.3.

Results

We identified 80 patients who developed de novo DEM-irAEs, comprising 15 from the present series and 65 from a literature review. Median age was 59 years (range: 9-84), with a male predominance (52/80 patients, 65%). DEMirAEs manifested after a median of 18 (range, 2-178) weeks following ICIs initiation (anti-PD1 [n=49,61%], anti-PD-L1 [n=4,5%] anti-CTLA4 [n=5,6%] and anti-PD1 + anti-CTLA4 [n=22,28%]). Clinical manifestations included: i) optic neuritis (n=17,8 bilateral); ii) myelitis (n=29,24 LETM) iii) ADEM (n=6); vi) atypical DEM-irAEs (n=7); vii) overlapping syndromes (n=21) . CSF restricted oligoclonal bands (12/50,24%) and autoantibodies against glial antigens (11/80,14% [MOG-IgG 3/51,6%; AQP4-IgG 5/53,9% and GFAP-IgG 3/35,9%]) were uncommon. Immunotherapy was administered in 93% of patients (intravenous steroids [n=61], IVIg [n=16], plasmapheresis [n=23], rituximab [n=8], and cyclophosphamide [n=8]). Among these patients 15 (24%) achieved a complete response, 25 (40%) a partial response, and 22 (35%) showed no response. Nineteen patients (17/66,26%) relapsed and 14 (18%,2 due for DEMirAEs –12 for cancer-related complications) died after a median follow-up of 7 (range 1-66) months.

Conclusions DEMirAEs presented as rare, heterogenous complication of ICI treatment. Long term immunosuppression should be considered in selected cases, as approximately one-quarter of patients may experience relapses.

Authors/Disclosures
Matteo Gastaldi, MD, PhD (IRCCS Mondino Foundation) PRESENTER	Dr. Gastaldi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for alexion, Roche, UCB, J&J. The institution of Dr. Gastaldi has received research support from Italian Ministry of Health, FISM, AE alliance.
Stefano Masciocchi, MD	Dr. Masciocchi has nothing to disclose.
Antonio Malvaso, MD (IRCCS Mondino Foundation)	Dr. Malvaso has nothing to disclose.
Kevin BIHAN, PharmD	Dr. BIHAN has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for MEDINSPIRE. Dr. BIHAN has stock in MEDINSPIRE. Dr. BIHAN has received intellectual property interests from a discovery or technology relating to health care.
Alessandro Dinoto, MD	The institution of Dr. Dinoto has received research support from Encephalitis International . The institution of Dr. Dinoto has received research support from Autoimmune Encephalitis Alliance.
Antonio Farina	Mr. Farina has nothing to disclose.
Alberto Picca, MD	Dr. Picca has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Servier.
Cristina Izquierdo, PhD	Dr. Izquierdo has nothing to disclose.
Lorena Martín-Aguilar, Jr., MD, PhD	Mrs. Martín-Aguilar has nothing to disclose.
Jordi Bruna (Hospital Universitari De Bellvitge - ICO Duran I Reynals)	Jordi Bruna has nothing to disclose.
Valentina Damato, MD, PhD (Department of Neuroscience, University of Florence)	Dr. Damato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Damato has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Damato has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB Pharma.
Elia Sechi, MD (University of Sassari)	Dr. Sechi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Sechi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Argenx.
Simone Rossi, MD	Dr. Rossi has nothing to disclose.
Nicola De Rossi	Nicola De Rossi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Nicola De Rossi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for novartis. Nicola De Rossi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen.
Helena Arino, MD, PhD	Dr. Arino has nothing to disclose.
Alvaro Cobo Calvo	Alvaro Cobo Calvo has nothing to disclose.
Sara Mariotto, MD, PhD (Neurology Unit, University of Verona)	Dr. Mariotto has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen, Sanofi, Alexion, Roche, TSF, Dynamics, UCB, Novartis, Amgen, AAN. The institution of Dr. Mariotto has received research support from Ministero della Salute Italiano. The institution of Dr. Mariotto has received research support from TSF. The institution of Dr. Mariotto has received research support from GJF. The institution of Dr. Mariotto has received research support from Lundbeck. The institution of Dr. Mariotto has received research support from Euroimmun. The institution of Dr. Mariotto has received research support from FISM.
Bastien Joubert (Hospices Civils de Lyon)	The institution of Bastien Joubert has received research support from French Ministry of Health. The institution of Bastien Joubert has received research support from CSL-Behring Immunology Foundation. Bastien Joubert has received publishing royalties from a publication relating to health care.
Enrico Marchioni	Enrico Marchioni has nothing to disclose.
Alberto Vogrig, MD, PhD (University of Udine)	Dr. Vogrig has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Eisai. Dr. Vogrig has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Angelini. The institution of Dr. Vogrig has received research support from Ministero della Salute, Bando Ricerca Finalizzata.

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