Recognition of the wide phenotype spectrum in immune checkpoint inhibitor-related neuropathy (irNeuropathy) and prompt management with corticosteroids may lead to favorable outcomes, according to results published in Neurology.

In this study, researchers used the Partners Research Patient Data Registry to search for relevant diagnostic codes or evaluations among patients who received immune checkpoint inhibitors at the Massachusetts General Hospital and Brigham and Women’s Hospital. Researchers identified 19 patients with Inhibitor-Related Neuropathy (Massachusetts General Hospital [n=16], Brigham and Women’s Hospital [n=3]) and compared their clinical characteristics with neuropathy caused by cytotoxic agents.

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Patients received immune checkpoint inhibitors including antiprogrammed death-1 (n=9), programmed death–1 receptor ligand (pembrolizumab [n=4], nivolumab [n=4], atezolizumab [n=1]), anti-cytotoxic T lymphocyte-associated antigen 4 (n=2), and both anti-cytotoxic T lymphocyte-associated antigen 4 and anti-programmed death-1 therapy (ipilimumab and nivolumab [n=7], ipilimumab and pembrolizumab [n=1]) in combination or sequentially. Patients received a median number of 4 doses (range 1 to 26) before the development of neuropathy.

Results revealed the median time of initiation with immune checkpoint inhibitor to symptom onset was 9 weeks (range 1-104 weeks). The rate of irNeuropathies following therapy onset was 0.7%. Underlying malignancies included melanoma (n=15), lung adenocarcinoma (n=3), and cholangiocarcinoma (n=1). Neuropathy phenotypes included cranial neuropathies with or without meningitis (n=7), nonlength-dependent polyradiculoneuropathies (n=6) with or without cranial nerve involvement, small-fiber/autonomic neuropathy (n=2), neuralgic amyotrophy (n=1), sensory neuronopathy (n=1), antineutrophil cytoplasmic antibody-associated mononeuritis-multiplex (n=1), and length-dependent sensorimotor axonal polyneuropathy (n=1).

The most common cranial neuropathy phenotype was facial nerve palsy with or without meningitis (n=5). Immune-related adverse events involving other organ systems were seen in 58% of patients (n=11), and central nervous system or meningeal involvement was seen in 36% of patients (n=7).

Oral or intravenous corticosteroids were used to manage irNeuropathy in 11 patients, all of whom experienced improvements in modified Rankin Scale score (P =.001). Corticosteroid use for the management of irNeuropathy was also associated with improvement in inflammatory neuropathy cause and treatment disability scores (P =.012). Rate of hospitalization for irNeuropathy was higher (P =.002) compared with toxic neuropathy from chemotherapy.

Limitations of this study included its retrospective design and the fact that cases were limited to those from Massachusetts General Hospital. Further, the rate of immune-related adverse events may have been influenced by the doses of immune checkpoint inhibitors used and the rate of neuropathy may have been underestimated and lesser-grade neuropathies missed due to mild numbness or weakness not identified by search criteria. The varied doses of corticosteroids used limited the researcher’s recommendations for an optimal management strategy of irNeuropathies.

The researchers note that while neuropathy is a rare complication of immune checkpoint inhibitors that often responds to immunosuppression,” it is important to recognize the phenotypic spectrum is wide. Evaluate the distinct clinical characteristics of each presentation and “prompt management with corticosteroids” may result in to favorable outcomes.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Dubey D, David WS, Amato AA, et al. Varied phenotypes and management of immune checkpoint inhibitor-associated neuropathies [published online August 12, 2019]. Neurology. doi: 10.1212/WNL.0000000000008091