Multiple Sclerosis Disease Activity is Uncommon in Individuals With Pre-existing Multiple Sclerosis Exposed to Immune Checkpoint Inhibitor Therapy
Alexander Gill1, Jonathan Krett2, Carson Quinn3, Prashanth Rajarajan3, Lyndsey Babcock4, Anna Kaiser5, Andrew Morrison6, Thomas Pisano6, Atika Paracha7, Cory Dodson8, Hannah Kopinsky9, Iwalewa Moninuola10, Said Alhassan11, Wendy Stewart12, Maria Aguilera-Pena13, Sofia Ramierz Guerrero13, Nikhil Modak10, Maxime Jean14, Jessica Lamb15, Yoav Piura16, Jordan CARRIER14, Muhammed Ikbal Arvas17, Celeste Camargo18, Vikram Bhise18, Jenny Linnoila5, Vinay Chaudhry11, Shamik Bhattacharyya3, Enrique Alvarez4, Daniel Kantor19, Flavia Nelsion20, Kottil Rammohan20, Patricia Coyle15, Lauryn Hemminger14, Nicole Baldwin20, George Hutton17, Alexandra Simpson12, Paula Barreras13, Irena Dujmovic Basuroski11, Cole Harrington10, Anne Douglas6, Gregory Day16, Ilya Kister9, Kristin Galetta8, Sarah Conway3, Shuvro Roy7, Sachin Gadani5, Andrew Wolf4, John Probasco2
1Autoimmune Neurology Research Consortium (ANRC), 2Department of Neurology, Johns Hopkins School of Medicine, 3Department of Neurology, Mass General Brigham, 4Department of Neurology, University of Colorado School of Medicine, 5Department of Neurology, University of Pittsburgh, 6Department of Neurology, Hospital of the University of Pennsylvania, 7Department of Neurology, University of Washington, 8Department of Neurology, Stanford University, 9Department of Neurology, New York University Grossman School of Medicine, 10Department of Neurology, The Ohio State University Wexner Medical Center, 11Department of Neurology, University of North Carolina School of Medicine, 12Department of Neurology, University of Virginia School of Medicine, 13Department of Neurology, Cedars-Sinai Medical Center, 14Department of Neurology, University of Rochester, 15Department of Neurology, Stony Brook Medicine, 16Department of Neurology, Mayo Clinic, 17Department of Neurology, Baylor College of Medicine, 18Department of Neurology, Rutgers-Robert Wood Johnson Medical School, 19Medical Partnership 4 MS+, 20Department of Neurology, University of Miami
Objective:
To determine neurologic outcomes in people with multiple sclerosis (pwMS) after exposure to immune checkpoint inhibitors (ICIs) for comorbid oncologic indications.
Background:
ICI therapy is associated with immune-related adverse events (irAEs) including de novo CNS demyelinating events and pre-existing autoimmune diseases exacerbations.
Design/Methods:
PwMS treated with ICIs for comorbid oncologic indications were identified by systematic retrospective chart review at 18 tertiary medical centers and outcomes were obtained using a structured data instrument.
Results:
We identified 165 individuals (72% female) with MS who were treated with ICIs. Median age at time of ICI initiation was 63 years old. During a median of 6 months of ICI therapy, 6 pwMS (3.6%) were diagnosed with an MS clinical relapse after ICI initiation, 2 of which occurred > 6 months after last ICI dose. Of these, 3 had full and 3 had partial clinical recovery. Seven additional subjects (4.2%) had new MS lesions on MRI post-ICI without associated clinical relapse, 2 of which occurred > 6 months after last ICI dose. One of 33 (3%) and 8 of 132 (6%) pwMS who were ≤55yo or >55yo, respectively, had evidence of MS disease activity post-ICI and within 6 months of last ICI dose. Ten of 33 (30%) and 34 of 132 (26%) pwMS who were ≤55yo or >55yo, respectively, were continued on disease-modifying therapy at ICI initiation. One of 19 (5.3%) and 3 of 68 (4.4%) of pwMS with their last documented MS clinical relapses ≤5 or >5 years pre-ICI, respectively, had evidence of disease activity post-ICI and within 6 months of last ICI dose. Eleven pwMS (6.7%) had non-MS neurologic irAEs and 36 (21%) had non-neurologic irAEs.
Conclusions:
In this retrospective cohort study of pwMS, MS disease activity following ICI treatment was uncommon, including in younger individuals and those with more recent MS clinical disease activity.
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