Kao JC, et al. - An inquiry was set up with regard to the frequency, clinical spectrum, and optimum treatment approach to neurological complications linked with anti–programmed death 1 (PD-1) therapy. A diverse phenotype, with more frequent neuromuscular complications, were reported by the neurological adverse events related to anti–PD-1 therapy. In spite of being rare, they exhibited a tendency of being encountered with increasing frequency as anti–PD-1 therapy expanded to other cancers. It displayed unpredictable time of onset with a possible rapid evolution, which could be life-threatening. Hence, the data suggested prompt recognition and discontinuation of anti–PD-1 therapy. Few cases could warrant immune rescue treatment.

Methods

• The plot of this research was a single-center, retrospective cohort study.
• It was performed from either September or December 2014 (the approval dates of the study drugs by the US Food and Drug Administration) to May 19, 2016.
• It recruited patients receiving anti–PD-1 monoclonal antibodies through the Mayo Cancer Pharmacy Database.
• Patients with development of neurological symptoms within 12 months of anti–PD-1 therapy were selected.
• The exclusion criteria involved patients with neurological complications directly attributable to metastatic disease or other concurrent cancer-related treatments.The clinical and pathological characteristics, time to development of neurological symptoms, and modified Rankin Scale (mRS) score were included as the main outcome measure.

Results

• 10 (2.9%) patients developed subacute onset of neurological complications, among 347 patients treated with anti-PD1 monoclonal antibodies (pembrolizumab or nivolumab).
• Herein, seven patients were receiving pembrolizumab, and 3 patients were receiving nivolumab.
• The enrollees included 8 men and 2 women. Their median age was 71 years (age range, 31-78 years).
• During this study, neurological complications were reported following a median of 5.5 (range, 1-20) cycles of anti-PD-1 inhibitors.
• Complications presented with myopathy (n = 2), varied neuropathies (n = 4), cerebellar ataxia (n = 1), autoimmune retinopathy (n = 1), bilateral internuclear ophthalmoplegia (n?=?1), and headache (n?=?1).
• Axonal and demyelinating polyradiculoneuropathies (n?=?2), length-dependent neuropathies (n?=?1), and asymmetric vasculitic neuropathy (n?=?1) were the peripheral neuropathies.
• A variation was noted in the time to maximum symptom severity from 1 day to more than 3 months.
• It was noted that the median mRS score was 2.5 (range, 1-5), indicating mild to moderate disability.
• Five patients reported other systemic immune-mediated complications, including hypothyroidism (n?=?3), colitis (n?=?2), and hepatitis (n?=?1).
• Treatment with anti–PD-1 antibodies was discontinued in 7 patients.
• The therapy given included corticosteroids (n?=?7), intravenous immunoglobulin (n?=?3), and plasma exchange (n?=?1).
• An improvement was seen in nine patients, with a median mRS score of 2 (range, 0-6).
• One patient with severe necrotizing myopathy died.