Researchers at The University of Texas MD Anderson Cancer Center have made significant progress in treating leptomeningeal disease (LMD) caused by metastatic melanoma. LMD is a complication of cancer where cancer cells from primary tumors spread into the cerebrospinal fluid (CSF) and leptomeninges, the outer lining of the brain and spinal cord.
This condition affects around 10% of patients with stage IV melanoma and is also common in metastatic lung and breast cancer. Although there is no cure, targeted therapy and immunotherapy may improve the quality of life for patients.
In a first-of-its-kind study published in Nature Medicine, the researchers conducted a Phase I/Ib trial to assess the safety and effectiveness of a new approach that involved concurrent intrathecal (IT) and intravenous (IV) administration of immunotherapy using nivolumab (anti-PD-1). A total of 25 patients were enrolled, with a median overall survival (OS) of 4.9 months. The study showed encouraging OS rates of 44% at 26 weeks and 26% at 52 weeks, with four patients surviving significantly longer than expected.
The treatment was well tolerated, with only mild side effects and no dose-limiting toxicities. Common treatment-related adverse events included nausea, dizziness, and vomiting. This novel approach is considered a major step forward in addressing the unmet clinical need for better treatments for LMD patients.
Previous studies by the same researchers have shown that IT administration of interleukin-2 had promising results but was linked to serious side effects. The current trial demonstrated that injecting nivolumab directly into the spinal fluid increases its concentration within the CSF, as these antibodies cannot easily penetrate the blood-brain barrier.
The enrolled patients had a median age of 43, and most had received prior systemic therapy, including immune checkpoint inhibitors (84%), BRAF/MEK inhibitors (64%), and chemotherapy (12%). The trial evaluated four doses of IT nivolumab alongside a flat dose of IV nivolumab.
The researchers are optimistic that these results, combined with further clinical trials, will lead to a better understanding of LMD and more effective treatment options for patients. The study has recently completed enrollment for the dose-expansion cohort, and analysis is underway to provide further insights. Ongoing research will also aim to identify biomarkers that may predict which patients are most likely to benefit from this innovative treatment approach.
Key Takeaways in a Nutshell – Health Newstrack
– Researchers at The University of Texas MD Anderson Cancer Center have made progress in treating leptomeningeal disease (LMD) caused by metastatic melanoma, a complication affecting around 10% of stage IV melanoma patients.
– A first-of-its-kind study published in Nature Medicine involved concurrent intrathecal (IT) and intravenous (IV) administration of immunotherapy using nivolumab (anti-PD-1) in 25 patients, with encouraging survival rates and well-tolerated side effects.
– Injecting nivolumab directly into the spinal fluid increases its concentration within the cerebrospinal fluid (CSF), as these antibodies cannot easily penetrate the blood-brain barrier.
– The researchers are optimistic that these results, combined with further clinical trials, will lead to a better understanding of LMD and more effective treatment options for patients.
– Ongoing research aims to identify biomarkers that may predict which patients are most likely to benefit from this innovative treatment approach.