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J Neurooncol. 2018 May;137(3):601-609. doi: 10.1007/s11060-018-2752-5. Epub 2018 Jan 13.

Neurologic complications of immune checkpoint inhibitors.

Author information

1
Department of Neurology, Rabin Medical Center, Beilinson Hospital, 39 Jabotinski St., Petah Tikva, Israel. avi.fellner@gmail.com.
2
Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel. avi.fellner@gmail.com.
3
Department of Oncology, Leslie and Michael Gaffin Center for Neuro-Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
4
Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
5
Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
6
Neuro-Oncology Service, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
7
Oncology Institute, Sheba Medical Center, Ramat-Gan, Israel.
8
Department of Neurology, Baylor College of Medicine, Houston, TX, USA.
9
Department of Pathology, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel.
10
Department of Neurology, Rabin Medical Center, Beilinson Hospital, 39 Jabotinski St., Petah Tikva, Israel.
11
Neuro-Oncology Unit, Davidoff Cancer Center at Rabin Medical Center, Petah Tikva, Israel.

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.

KEYWORDS:

CTLA-4; Immune checkpoint inhibitors; Neurological complications; PD-1

PMID:
29332184
DOI:
10.1007/s11060-018-2752-5
[Indexed for MEDLINE]

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