Researchers have found that a novel approach to administering intrathecal and intravenous nivolumab has proven safe and improved survival in a subset of patients who developed leptomeningeal disease from metastatic melanoma, according to a new study published by Glitza Olivia et al in Nature Medicine. In a phase I/Ib trial, researchers enrolled 25 patients with a median age of 43 years who had mostly received prior systemic therapy—including 84% who had received immune checkpoint inhibitors, 64% who had received BRAF/MEK inhibitors, and 12% who had received chemotherapy. The dose-expansion cohort evaluated four doses of intrathecal nivolumab concurrent with a flat dose of intravenous nivolumab. Among the 25 patients, median overall survival was 4.9 months, with a 44% overall survival rate after 26 weeks and 26% survival rate after 52 weeks. Four patients survived to 74, 115, 136, and 143 weeks, respectively, after their first intrathecal dose of nivolumab. Intrathecal nivolumab was well tolerated at its highest dose level, with only mild grade 1 or 2 side effects and no dose-limiting toxicities. The most common treatment-related adverse events were nausea, dizziness, and vomiting.
In a companion press release on the findings from The University of Texas MD Anderson Cancer Center, corresponding author Isabella Glitza Oliva, MD, PhD, Associate Professor of Melanoma Medical Oncology, commented, “This represents a major path forward for our patients, as there is a crucial unmet clinical need for better treatments for patients with leptomeningeal disease…. We are encouraged by these preliminary results for a disease that has been notoriously difficult to study due to its highly aggressive nature. This approach is safe, and we’re seeing a small subset of our patients who have had outstanding results, so we hope to learn from each and every one of them.”