PT  - JOURNAL ARTICLE
AU  - Dubey, Divyanshu
AU  - David, William S.
AU  - Amato, Anthony A.
AU  - Reynolds, Kerry L.
AU  - Clement, Nathan F.
AU  - Chute, Donald F.
AU  - Cohen, Justine V.
AU  - Lawrence, Donald P.
AU  - Mooradian, Meghan J.
AU  - Sullivan, Ryan J.
AU  - Guidon, Amanda C.
TI  - Varied phenotypes and management of immune checkpoint inhibitor-associated neuropathies
AID  - 10.1212/WNL.0000000000008091
DP  - 2019 Sep 10
TA  - Neurology
PG  - e1093--e1103
VI  - 93
IP  - 11
4099  - http://n.neurology.org/content/93/11/e1093.short
4100  - http://n.neurology.org/content/93/11/e1093.full
SO  - Neurology2019 Sep 10; 93
AB  - Objective To describe the spectrum, clinical course, and management of neuropathies associated with immune checkpoint inhibitors (ICIs).Methods Patients with ICI-related neuropathy (irNeuropathy) were identified and their clinical characteristics compared to neuropathy attributed to cytotoxic agents.Results We identified 19 patients with irNeuropathies. ICIs included anti-programmed death–1 (PD1), 9; anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA4), 2; and combination of anti-CTLA4 and anti-PD1, 8. Median number of ICI doses prior to neuropathy onset was 4. Rate of neuropathies following ICI therapy was 0.7%. Underlying malignancies included melanoma (n = 15), lung adenocarcinoma (n = 3), and cholangiocarcinoma (n = 1). Neuropathy phenotypes were cranial neuropathies with or without meningitis (n = 7), nonlength-dependent polyradiculoneuropathies with and without cranial nerve involvement (n = 6), small-fiber/autonomic neuropathy (n = 2), ANCA-associated mononeuritis multiplex (n = 1), sensory neuronopathy (n = 1), length-dependent sensorimotor axonal polyneuropathy (n = 1), and neuralgic amyotrophy (n = 1). Immune-related adverse events involving other organ systems were common (58%). Corticosteroid use for management of neuropathy was associated with improvement in median modified Rankin Scale score (1 vs 0, p = 0.001) and Inflammatory Neuropathy Cause and Treatment Disability score (2 vs 0.5, p = 0.012) (Class IV). Significantly higher proportion of irNeuropathies had acute or subacute and nonlength-dependent presentations (p < 0.001) and rate of hospitalization for irNeuropathy was also higher (p = 0.002) compared to toxic neuropathy from chemotherapy.Conclusion Neuropathy is a rare complication of ICIs that often responds to immunosuppression. Recognition of its wide phenotypic spectrum and distinct clinical characteristics and prompt management with corticosteroids may lead to favorable outcomes.BWH=Brigham and Women's Hospital; CTCAE=Common Terminology Criteria for Adverse Events; CTLA4=cytotoxic T lymphocyte-associated antigen 4; ICI=immune checkpoint inhibitor; INCAT=Inflammatory Neuropathy Cause and Treatment; irAE=immune-related adverse event; IVIg=IV immunoglobulin; LP=lumbar puncture; MGH=Massachusetts General Hospital; mRS=modified Rankin Scale; PD1=programmed death–1 receptor; PDL1=programmed death–1 receptor ligand; TNC=total nucleated cell