Abstract
Immune checkpoint inhibitors (ICPIs) have recently emerged as a novel treatment for cancer. These agents, transforming the field of oncology, are not devoid of toxicity and cause immune-related side effects which can involve any organ including the nervous system. In this study, we present 9 patients (7 men and 2 women) with neurologic complications secondary to ICPI treatment. These included meningoencephalitis, limbic encephalitis, polyradiculitis, cranial polyneuropathy, myasthenic syndrome and myositis. Four patients received dual ICPI therapy comprised of programmed cell death-1 and cytotoxic lymphocyte associated protein-4 blocking antibodies. Median time to onset of neurologic adverse event during immune checkpoint inhibitor treatment was 8 weeks (range 5 days–19 weeks). In all patients ICPIs were stopped and corticosteroids were initiated, resulting in a marked improvement in seven out of nine patients. Two patients, one with myositis and one with myasthenic syndrome, died. In two patients ICPI therapy was resumed after resolution of the neurological adverse event with no additional neurologic complications. This series highlights the very broad spectrum of neurological complications of ICPIs, emphasizes the need for expedited diagnosis and suggests that withholding treatment early, accompanied with steroid therapy, carries the potential of complete resolution of the neurological immune-mediated condition. Thus, a high level of suspicion and rapid initiation of corticosteroids are mandatory to prevent uncontrolled clinical deterioration, which might be fatal.
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This case study received an approval from the Head of Institutional Review Board (Helsinki Committee) of Rabin Medical Center, Petah Tikva, Israel. This study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
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Israeli regulations do not require consent for case report or case series, provided that they are anonymous. This manuscript is a retrospective study, does not contain clinical studies and the data in this case series do not disclose the identities of the patients.
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Fellner, A., Makranz, C., Lotem, M. et al. Neurologic complications of immune checkpoint inhibitors. J Neurooncol 137, 601–609 (2018). https://doi.org/10.1007/s11060-018-2752-5
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DOI: https://doi.org/10.1007/s11060-018-2752-5