Divyanshu Dubey1, William S David1, Anthony A Amato1, Kerry L Reynolds1, Nathan F Clement1, Donald F Chute1, Justine V Cohen1, Donald P Lawrence1, Meghan J Mooradian1, Ryan J Sullivan1, Amanda C Guidon2. 1. From the Departments of Neurology (D.D., W.S.D., A.C.G.), Medicine (K.L.R., D.F.C., J.V.C., D.P.L., M.J.M., R.J.S.), and Pathology (N.F.C.), Massachusetts General Hospital; Department of Neurology (D.D., A.A.A.), Brigham and Women's Hospital, Boston, MA; and Department of Neurology (D.D.), Mayo Clinic, Rochester, MN. 2. From the Departments of Neurology (D.D., W.S.D., A.C.G.), Medicine (K.L.R., D.F.C., J.V.C., D.P.L., M.J.M., R.J.S.), and Pathology (N.F.C.), Massachusetts General Hospital; Department of Neurology (D.D., A.A.A.), Brigham and Women's Hospital, Boston, MA; and Department of Neurology (D.D.), Mayo Clinic, Rochester, MN. aguidon@mgh.harvard.edu.
Abstract
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.
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.
Authors: Elia Sechi; Svetomir N Markovic; Andrew McKeon; Divyanshu Dubey; Teerin Liewluck; Vanda A Lennon; A Sebastian Lopez-Chiriboga; Christopher J Klein; Michelle Mauermann; Sean J Pittock; Eoin P Flanagan; Anastasia Zekeridou Journal: Neurology Date: 2020-08-13 Impact factor: 9.910
Authors: Julie R Brahmer; Hamzah Abu-Sbeih; Paolo Antonio Ascierto; Jill Brufsky; Laura C Cappelli; Frank B Cortazar; David E Gerber; Lamya Hamad; Eric Hansen; Douglas B Johnson; Mario E Lacouture; Gregory A Masters; Jarushka Naidoo; Michele Nanni; Miguel-Angel Perales; Igor Puzanov; Bianca D Santomasso; Satish P Shanbhag; Rajeev Sharma; Dimitra Skondra; Jeffrey A Sosman; Michelle Turner; Marc S Ernstoff Journal: J Immunother Cancer Date: 2021-06 Impact factor: 13.751