PD-1 Therapy for Cancer Increases Risk for Neurological Complications
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."
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