Atypical neurological complications of ipilimumab therapy in patients with metastatic melanoma.
BACKGROUND
Ipilimumab is a novel FDA-approved recombinant human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 and has been used to treat patients with metastatic melanoma. Immune-related neurological adverse effects include inflammatory myopathy, aseptic meningitis, posterior reversible encephalopathy syndrome, Guillain-Barré syndrome, myasthenia gravis-type syndrome, sensorimotor neuropathy, and inflammatory enteric neuropathy. To date, there is no report for ipilimumab-induced chronic inflammatory demyelinating polyneuropathy (CIDP), transverse myelitis (TM), or concurrent myositis and myasthenia gravis-type syndrome. Our objective is to raise early recognition of atypical neurological adverse events and to share our therapeutic approach.


METHODS
We report 3 cases of metastatic melanoma treated with ipilimumab in which the patients developed CIDP, TM, and concurrent myositis and myasthenia gravis-type syndrome, respectively, at the MD Anderson Cancer Center between July 2012 and June 2013. Patients consented to release of medical information for publication/educational purposes.


RESULTS
Our 3 cases of metastatic melanoma treated with ipilimumab developed CIDP, TM, and concurrent myositis and myasthenia gravis-type syndrome, respectively. The median time to onset of immune-related adverse events following ipilimumab treatment ranged from 1 to 2 weeks. Ipilimumab was discontinued due to the severe neurological symptoms. Plasmapheresis was initiated in the patients with CIDP and concurrent myositis and myasthenia gravis-type syndrome; high-dose intravenous steroids were given to the patient with TM, and significant clinical response was demonstrated.


CONCLUSIONS
Ipilimumab could induce a wide spectrum of neurological adverse effects. Our findings support the standard treatment of withholding or discontinuing ipilimumab. Plasmapheresis or high-dose intravenous steroids may be considered as the initial choice of treatment for severe ipilimumab-related neurological adverse events. Improvement of neurological symptoms may be seen within 2 weeks.
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (B.L., S.S., C.K.-M., S.T.); Department of Neurology, The University of Texas Medical Branch, Galveston, Texas (B.L., S.S., C.K.-M.).
Bing
B
Liao
Sheetal
S
Shroff
Carlos
C
Kamiya-Matsuoka
Sudhakar
S
Tummala
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000556:secondary; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D008113:Liver Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008545:Melanoma / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D011379:Prognosis
D000911:Antibodies, Monoclonal; D000074324:Ipilimumab
chronic inflammatory demyelinating polyneuropathy; immune-related adverse events; ipilimumab; metastatic melanoma; transverse myelitis