PD-1 Therapy for Cancer Increases Risk for Neurological Complications

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Neurological complications occur in approximately 4.2% of patients undergoing treatment with PD-1 therapy.
Neurological complications occur in approximately 4.2% of patients undergoing treatment with PD-1 therapy.

Anti-programmed death 1 (PD-1) therapy is associated with a small risk for neurological complications among patients treated for metastatic cancer, according to a retrospective study reported in JAMA Neurology.

Researchers included 347 patients who were treated with anti-PD1 monoclonal antibodies (pembrolizumab or nivolumab) for malignant melanoma or solid-organ tumors.

Subacute onset of neurological complications developed in 10 patients (2.9%) receiving treatment with either pembrolizumab (n=7) or nivolumab (n=3). The median age of these patients was 71 years (age range, 31-78 years). The investigators observed the occurrence of neurological complications after a median of 5.5 therapy cycles. Among these patients, complications included varied neuropathies (n=4), autoimmune retinopathy (n=1), myopathy (n=2), bilateral internuclear ophthalmoplegia (n=1), cerebellar ataxia (n=1), and headache (n=1).

Median modified Rankin Scale score, which measured dependence in daily activities, was 2.5 (range, 1-5), suggesting neurological complications associated with anti-PD-1 antibodies lead to mild to moderate disability. Discontinuation of anti-PD-1 therapy was reported in 7 patients, with 30 days representing the average duration of symptoms until the start of immune treatment. Of patients receiving corticosteroids (n=7), intravenous immunoglobulin (n=3), and plasma exchange (n=1), 9 improved and 1 patient died with severe necrotizing myopathy.

Because this study included a small number of patients and a specific focus on incidence of complications, the findings failed to provide conclusive evidence for an optimum treatment strategy of the therapy-associated complications.

Although neurological complications may rapidly evolve to becoming life-threatening, the investigators noted that early identification and treatment for these complications may generate favorable outcomes for patients. In addition, the researchers believe that clinicians "will likely encounter more cases [of complications] in the future as the use of these medications in the treatment of metastatic cancer continues to expand."

Reference

Kao JC, Liao B, Markovic SN, et al. Neurological complications associated with anti-programmed death 1 (PD-1) antibodies [published online September 5, 2017]. JAMA Neurol. doi: 10.1001/jamaneurol.2017.1912

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