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Abstract: FR-PO265

Beyond Tumor Regression: Exploring the Fatal Consequences of Immune Checkpoint Inhibitor (ICI)-Induced Triple M Syndrome and Myoglobin Nephropathy

Session Information

Category: Onconephrology

  • 1700 Onconephrology


  • Sheikh, M. Salman, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Chowdhury, Raad Bin Zakir, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Leung, Nelson, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. Despite showing remarkable tumor regressions and anti-tumor efficacy, these agents can also lead to life-threatening immune-related adverse events (irAEs). One exceedingly rare irAE is ICI-induced myocarditis with myositis/myasthenia overlap, also known as Triple M Syndrome. We present a case of Triple M Syndrome with acute kidney injury and provide a review of the clinical course.

Case Description

A 76-year-old male with melanoma was treated with a single dose of adjuvant Nivolumab. Two weeks later, he was admitted with sudden-onset angina, respiratory failure requiring emergent intubation, and neurological symptoms. Physical exam revealed bilateral ptosis, diplopia, and proximal muscle flaccid paralysis. Laboratory workup was notable for increasing troponins to 4783ng/L, markedly elevated liver enzymes, and elevated creatinine kinase (CK) of 6806 U/L. Serum myoglobin was elevated to 3799 mcg/L, aldolase was 100 U/L, and acetylcholine receptor antibodies were detected. EKG did not show ischemic features. Electromyography demonstrated significant abnormalities. The patient was diagnosed with ICI-induced myocarditis, myositis, and myasthenia gravis. Pulse dose steroid therapy was administered followed by plasma exchange. Persistent elevation of serum and urine myoglobin, even after CK normalization, resulted in pigment nephropathy requiring continuous renal replacement therapy (CRRT). Anti-thymoglobulin was administered for refractory irAE- but no benefit was observed. He ultimately expired. Autopsy revealed severe tubular injury with myoglobin casts, no ICI related interstitial findings, and focal lymphocytic myocarditis.


This case presents Triple M Syndrome, an irAE characterized by myocarditis, myositis, and myasthenia overlap. The patient exhibited profound elevation in troponin and myoglobin levels, while CK levels were less remarkable. This suggests a predominant myocardial injury with a lesser extent of skeletal muscle involvement. Important to note is that the diagnosis of myositis relied on troponin and CK, while CK and myoglobin were necessary for diagnosing myoglobin pigment nephropathy. In summary, recognizing Triple M Syndrome as an irAE causing renal injury from myoglobin, and not necessarily only interstitial disease, is crucial.