Melanoma Brain Metastases: Can Nivolumab and Ipilimumab Cross the Blood-Brain Barrier?
Posted: Tuesday, July 23, 2019
Immune checkpoint inhibitors such as nivolumab and ipilimumab are active in the treatment of brain metastases from melanoma, and both can penetrate an intact blood-brain barrier despite being a large monoclonal antibody. Mark T. J. van Bussel, MSc, of the Netherlands Cancer Institute, Amsterdam, and colleagues published a systemic review in BMC Cancer providing pharmacodynamic and pharmacokinetic information about the two drugs in this patient population.
“The highly promising clinical antitumor activity combined with the described mechanism of penetration of monoclonal antibodies into the [cerebrospinal fluid] opens novel strategies to treat malignant diseases in the central nervous system,” concluded the authors.
The study was conducted by a literature search to find prospective phase II and III studies on nivolumab and ipilimumab in patients with brain metastases from melanoma. Studies were included if they had information regarding cerebrospinal fluid (CSF) levels of the two drugs. The team identified two phase II studies with the combination of both drugs along with one phase II study with ipilimumab monotherapy for this indication. Only one of these three studies reported the CSF level with nivolumab.
The phase II study using nivolumab and ipilimumab showed intracranial responses in 16 of 35 total patients (46%). Another study showed a rate of intracranial benefit of 57% for the combination therapy. The ratio of CSF level to serum for nivolumab was 0.88% to 1.9% in a group of patients treated with 1 to 3 mg/kg of nivolumab. The concentration of nivolumab in patients ranged from 35 to 150 ng/mL of CSF, near the half maximal effective concentration of 0.64 nM.
Disclosure: The study authors reported no conflicts of interest.