RT Journal Article
SR Electronic
T1 Varied phenotypes and management of immune checkpoint inhibitor-associated neuropathies
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP e1093
OP e1103
DO 10.1212/WNL.0000000000008091
VO 93
IS 11
A1 Dubey, Divyanshu
A1 David, William S.
A1 Amato, Anthony A.
A1 Reynolds, Kerry L.
A1 Clement, Nathan F.
A1 Chute, Donald F.
A1 Cohen, Justine V.
A1 Lawrence, Donald P.
A1 Mooradian, Meghan J.
A1 Sullivan, Ryan J.
A1 Guidon, Amanda C.
YR 2019
UL http://n.neurology.org/content/93/11/e1093.abstract
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