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Abstract Details

Immune checkpoint inhibitor-associated myopathy: Clinicoseropathological Phenotype and Survival Analysis
Neuromuscular and Clinical Neurophysiology (EMG)
Neuromuscular and Clinical Neurophysiology (EMG) Posters (7:00 AM-5:00 PM)
126
Expand current knowledge of immune checkpoint inhibitor-associated myopathy (ICIAM).
Immune checkpoint inhibitors (ICI) have revolutionized the landscape of cancer treatment. Alongside their many advantages, they elicit immune-related adverse events, including myopathy.

Five-year retrospective study of patients with ICIAM. Clinical features, survival and ancillary test findings were analyzed and compared with those of immune-mediated necrotizing myopathy (IMNM).
We identified 24 ICIAM (median age 69 years; range: 28-86) and 38 IMNM patients. Ocular involvement occurred in 9/24 ICIAM patients, without electrodiagnostic evidence of neuromuscular transmission defect, and in none of IMNM patients (P<0.001). Myocarditis occurred in 8 ICIAM and in none of IMNM patients (P<0.001). Median creatine kinase (CK) was significantly lower in ICIAM cohort, 686 IU/L (7 with normal CK), compared to IMNM cohort, 6456 IU/L (P<0.001). Myopathological findings were similar between ICIAM and IMNM patients, consisting of necrotic fibers with no or subtle inflammation. Necrotic fibers however arranged in clusters in 10/11 ICIAM patients but not in IMNM patients (P<0.001). Despite the lower CK levels in ICI exposed patients, the number of necrotic fibers was similar in both groups. Mitochondrial abnormalities were higher in ICIAM (P<0.001).  Anti-HMGCR (Hydroxy-3-Methylglutaryl-CoA Reductase) or SRP (signal recognition particle) antibodies were absent in ICIAM patients but positive in two-thirds of IMNM patients. Most patients with ICIAM responded favorably to immunomodulatory treatments, but 4 died from myopathy-related complications and 1 from myocarditis. Intubated patients had significantly shorter survival compared to non-intubated patients (median survival of 22 days; P=0.004).
ICIAM is a distinct, treatable immune-mediated myopathy with common ocular involvement and necrotizing histopathology, which contrary to IMNM, is featured by clusters of necrotic fibers and not accompanied by anti-HMGCR or SRP antibodies. Normal or mildly elevated CK level does not exclude the diagnosis.
Authors/Disclosures
Shahar Shelly, MD (Rambam Medical Center)
PRESENTER 		Dr. Shelly has or had stock in Remepy.
James D. Triplett, MBBS (Concord Hospital) Dr. Triplett has nothing to disclose.
Marcus Vinicius R. Pinto, MD (Mayo Clinic) Dr. Pinto has nothing to disclose.
Margherita Milone, MD, FÂ鶹´«Ã½Ó³»­ (Mayo Clinic) Dr. Milone has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cartesian Therapeutics. Dr. Milone has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Genetics, Â鶹´«Ã½Ó³»­. The institution of Dr. Milone has received research support from Mayo Clinic, CCaTS-CBD. The institution of Dr. Milone has received research support from Mayo Clinic, SGP Award. The institution of Dr. Milone has received research support from MDA for Care Center grant. The institution of Dr. Milone has received research support from Regenerative medicine Minnesota.
Felix E. Diehn, MD Dr. Diehn has nothing to disclose.
Anastasia Zekeridou, MD, PhD, FÂ鶹´«Ã½Ó³»­ (Neuroimmunology Laboratory, Mayo Clinic) The institution of Dr. Zekeridou has received research support from Roche/Genentech. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care.
Teerin Liewluck, MD, FÂ鶹´«Ã½Ó³»­ (Department of Neurology, Mayo Clinic) Dr. Liewluck has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta Therapeutics. Dr. Liewluck has received publishing royalties from a publication relating to health care.