Pembrolizumab-induced Triple M Overlap Syndrome, example of indiscriminate immune activation

Triple M Overlap Syndrome is an ultra-rare and seldom-described immune-related adverse event (irAE) secondary to pembrolizumab therapy. This entity and its namesake are due to auto-immune phenomena involving myocardium, striated muscle and neuromuscular junction, yielding a syndrome of myocarditis, myositis and myasthenia gravis. Since it was first identified in 1975, only 100 cases of this syndrome are found in the literature. With the increasing use of immune checkpoint inhibitors (ICIs) for the treatment of various malignancies, however, more cases are likely to be diagnosed in the future. We present a patient who received her first cycle of pembrolizumab therapy 3 weeks prior to presentation with complaints of intense myalgias, diffuse muscle weakness and ptosis. Investigative workup revealed myocarditis, myositis and myasthenia gravis. Treatment with high-dose steroids plus plasma exchange drastically improved her symptoms. This case demonstrates the presenting symptoms, diagnostic findings, critical complications and management strategies of Triple M Overlap Syndrome.