Table 7

irMyopathy

Subtypes:
(Median 8, range 7–9)
Possible symptoms:
(Median 8, range 7–9)
Supportive examination findings:
(Median 8, range 7–9)
Diagnostic criteria: All levels of diagnostic certainty for irMyopathy require a supportive history, examination, and timing relative to ICI therapy plus:
(Accuracy median 8, range 6–9; usability median 8, range 7–9)
  • Immune-mediated necrotizing myopathy

  • Inflammatory myopathy/myositis

Evaluate for overlapping irNMJ disorder and myocarditis; classify each disorder separately if present
  • Non-fluctuating weakness (ocular, bulbar, limb-girdle, axial, generalized, focal)

  • Absence of sensory symptoms

  • Myalgias

  • Dyspnea

  • Ptosis, diplopia

  • Head drop

  • Dysarthria, dysphonia

  • Dysphagia, nasal regurgitation

  • Fatigue

  • Myoglobinuria

  • Skin rash, scaling or dryness

  • Oculomotor weakness, ptosis

  • Dysarthria, dysphonia

  • Head drop (neck extension weakness), neck flexion weakness

  • Extremity weakness (proximal>distal, predilection for hip flexors)

  • Abnormally reduced pulmonary function testing (NIF/FVC)

  • Weakness is fixed without fatigability

  • Normal sensory examination

  • Skin changes associated with dermatomyositis (eg, heliotrope rash, malar rash, shawl sign, Gottron papules)

Definite
Required (1 of the following):
  1. Muscle tissue pathology (biopsy or autopsy) consistent with myositis or immune-mediated necrotizing myopathy OR

  2. EMG showing fibrillation potentials/positive sharp waves AND myopathic motor unit potentials (ie, short duration±low amplitude±early recruitment) OR

  3. MRI showing muscle STIR hyperintensity or contrast enhancement AND EMG showing myopathic motor units


Supportive when present but not required:
  1. Elevated CK

  2. Concurrent diagnosis of myocarditis


Required exclusion:
  1. No recent new exposure to other drugs associated with muscle necrosis or inflammation

  2. In the event of focal symptoms, no traumatic injury or mass lesion to explain

Evaluation may include:
(Median 8, range 7–9)
Probable
Required (1 of the following):
  1. EMG showing myopathic motor units (ie, brief duration, low amplitude, early recruitment) OR

  2. MRI showing muscle STIR hyperintensity or contrast enhancement OR

  3. Elevated CK OR

  4. Meets required criteria for definite category, but with an exclusion (ie, another plausible etiology may exist)

Common:
  1. CK, LFTs (with GGT if AST/ALT elevated)

  2. Electrodiagnostic studies (EMG/NCS) including needle EMG of clinically weak muscles and thoracic paraspinals. Repetitive nerve stimulation (RNS) of proximal nerve-muscle combinations often included

  3. Troponin, CK-MB, EKG, echocardiogram

Possible:
  1. Muscle biopsy of affected muscle

  2. MRI of affected limbs (with contrast if not contraindicated)

  3. Myositis-specific antibodies, anti-HGMCR ab

  4. ESR, CRP, ANA, aldolase

  5. AChR antibodies

  6. Complete or bedside pulmonary function tests (NIF/FVC)

  7. Fluoroscopic swallow evaluation

  8. Cardiac MRI if myocarditis suspected

Possible
Required:
  1. Supportive history and examination within timeframe of expected irAE but no additional workup performed OR

  2. Workup was not conclusive for irMyopathy but no other explanation for symptoms

Uncommon:
  1. Genetic testing

  2. Whole body FDG-PET (focus on skeletal muscle)

  • EMG, electromyography; FDG, fluorodeoxyglucose; ICI, immune checkpoint inhibitor.