Patients with metastatic melanoma developed fatigable ocular, bulbar and proximal muscle weakness 2 weeks after PD-1 inhibitor therapy.  Although their presentations were similar, patient 1 responded well to IVIG and systemic steroids (dosed on a gradually incrementing schedule appropriate for myasthenic exacerbation), while patient 2 failed to respond to aggressive immunotherapy including steroids, IVIG, plasmaphersis, and rituxan.

Patient 1, an 87 yo male, received pembrolizumab. Electrodiagnostic testing showed postsynaptic neuromuscular junction defect and needle EMG consistent with an irritable myopathy. CK was elevated to 1876 and anti-striated muscle antibody was positive at 1:1920.

Patient 2, a 79 yo male, received nivolumab.  Ice pack test was positive on initial examination but facial and spinal accessory motor responses could not be obtained for repetitive nerve stimulation.  Needle EMG was consistent with irritable myopathy.  CK was initially 3610 and striated muscle antibody was 1:245,760. Respiratory failure developed soon after presentation  requiring mechanical ventilation and the patient died 2 months later after developing complications of critical illness.

Both of these patients developed severe PD-1 inhibitor induced autoimmune neuromuscular disorders with overlap of primary muscle injury and post-synaptic neuromuscular junction dysfunction. These cases demonstrate the aggressive immune dysregulation that can occur with checkpoint inhibitors and the unique situation in which distinction between primary myositis and myasthenia is most challenging and important. This is not trivial as myositis, but not myasthenia, would arguably dictate aggressive high dose corticosteroids initially; similarly, persistent or progressive weakness would suggest escalation of immunotherapy in myasthenia but not advanced myositis where weakness is likely a result of degraded muscle fibers. The very high striated muscle antibody titer seen in case 1 may indicate a profound immune response predictive of poor response to therapy and higher mortality.