Varied phenotypes and management of immune checkpoint inhibitor-associated neuropathies

Divyanshu Dubey, William S. David, Anthony A. Amato, Kerry L. Reynolds, Nathan F. Clement, Donald F. Chute, Justine V. Cohen, Donald P. Lawrence, Meghan J. Mooradian, Ryan J. Sullivan, Amanda C. Guidon

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)e1093-e1103
JournalNeurology
Volume93
Issue number11
DOIs
StatePublished - Sep 10 2019

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CTLA-4 Antigen
Adrenal Cortex Hormones
Brachial Plexus Neuritis
Polyradiculoneuropathy
Mononeuropathies
Phenotype
Cranial Nerve Diseases
Antineutrophil Cytoplasmic Antibodies
Cholangiocarcinoma
Polyneuropathies
Cranial Nerves
Poisons
Cytotoxins
Meningitis
Immunosuppression
Melanoma
Hospitalization
Drug Therapy
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Dubey, D., David, W. S., Amato, A. A., Reynolds, K. L., Clement, N. F., Chute, D. F., ... Guidon, A. C. (2019). Varied phenotypes and management of immune checkpoint inhibitor-associated neuropathies. Neurology, 93(11), e1093-e1103. https://doi.org/10.1212/WNL.0000000000008091

Varied phenotypes and management of immune checkpoint inhibitor-associated neuropathies. / Dubey, Divyanshu; David, William S.; Amato, Anthony A.; Reynolds, Kerry L.; Clement, Nathan F.; Chute, Donald F.; Cohen, Justine V.; Lawrence, Donald P.; Mooradian, Meghan J.; Sullivan, Ryan J.; Guidon, Amanda C.

In: Neurology, Vol. 93, No. 11, 10.09.2019, p. e1093-e1103.

Research output: Contribution to journalArticle

Dubey, D, David, WS, Amato, AA, Reynolds, KL, Clement, NF, Chute, DF, Cohen, JV, Lawrence, DP, Mooradian, MJ, Sullivan, RJ & Guidon, AC 2019, 'Varied phenotypes and management of immune checkpoint inhibitor-associated neuropathies', Neurology, vol. 93, no. 11, pp. e1093-e1103. https://doi.org/10.1212/WNL.0000000000008091
Dubey D, David WS, Amato AA, Reynolds KL, Clement NF, Chute DF et al. Varied phenotypes and management of immune checkpoint inhibitor-associated neuropathies. Neurology. 2019 Sep 10;93(11):e1093-e1103. https://doi.org/10.1212/WNL.0000000000008091
Dubey, Divyanshu ; David, William S. ; Amato, Anthony A. ; Reynolds, Kerry L. ; Clement, Nathan F. ; Chute, Donald F. ; Cohen, Justine V. ; Lawrence, Donald P. ; Mooradian, Meghan J. ; Sullivan, Ryan J. ; Guidon, Amanda C. / Varied phenotypes and management of immune checkpoint inhibitor-associated neuropathies. In: Neurology. 2019 ; Vol. 93, No. 11. pp. e1093-e1103.
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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.",
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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.

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N2 - 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.

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.

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