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Soo Park, MD
Soo Park, MD
Posted: Wednesday, August 7, 2024
Because the prognosis of advanced melanoma with leptomeningeal disease remains less than ideal, Matthieu Faillot, MD, PhD, of Université Paris Cité, Assistance Publique hôpitaux de Paris, Beaujon Hospital, Clichy, and colleagues performed a study to determine whether intrathecally infused nivolumab is beneficial in this patient population. Presented during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 9522), the results of this study revealed three patients had a survival benefit, despite the survival data being inferior to prior analyses.
“Median nivolumab concentrations in cerebrospinal fluid were comparable to trough plasma concentrations at steady state after 3 mg/kg IV infusion,” concluded the investigators. “High plasma concentrations suggest rapid clearance of nivolumab from the cerebrospinal fluid, possibly related to reverse transcytosis of immunoglobulins.”
This retrospective study reviewed the data of 11 patients with advanced melanoma and leptomeningeal disease who were treated with a continuous intrathecal administration of the PD-1 inhibitor nivolumab. Participants received 10 to 13.5 mg/day of nivolumab administered through a catheter connected to an implanted pump, and nivolumab concentrations in cerebrospinal fluid were monitored.
The median follow-up was 2.5 months, and all patients experienced disease progression on systemic immunotherapy. Symptomatic leptomeningeal disease was identified in five patients, and eight had stable extracranial disease. The median duration of intrathecal treatment was 1.5 months. The median overall survival was 2.5 months, and survival rates at 3, 12, and 19 months were 36.4%, 27.3%, and 13.6%, respectively.
Extended survival, defined as at least 1 year, was reported in three patients; two patients had a survival duration of 19 months, and one had a survival duration of 12 months. Treatment-related adverse events included intracranial hypotension syndrome (n = 3), immune-mediated meningoencephalitis (n = 1), and hemorrhage on the catheter (n = 1). As expected, nivolumab concentrations in the plasma and cerebrospinal fluid among patients on 13.5 mg were higher than those on 10 mg.
Disclosure: Dr. Faillot reported no conflicts of interest. For full disclosures of the other study authors, visit coi.asco.org.
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