Checkpoint Modulation in Melanoma: An Update on Ipilimumab and Future Directions

“Ipilimumab, an anti-cytotoxic T-lymphocyte antigen 4 antibody, was the first therapy demonstrated to improve overall survival in melanoma. Since ipilimumab’s approval by the FDA in 2011, a wealth of data has amassed, helping clinicians to optimize its use. We have learned how to mitigate the adverse effects of ipilimumab, identified its effects in melanoma subpopulations such as those with brain metastases, uveal melanoma, and mucosal melanoma, discovered potential biomarkers of activity, and investigated its use in combination with other therapeutic modalities. These discoveries have paved the way for rapid development of second-generation immunomodulatory antibodies such as inhibitors of the programmed cell death 1 receptor axis. These new agents hold promise as monotherapy, but perhaps the greatest allure lies in the possibility of combining these agents in synergistic multidrug regimens.”

Approved Immunotherapy Extends Life After Melanomas Have Spread to the Brain

An FDA-approved immunotherapy was thought to be too risky for people with melanomas that have spread to the brain—but a new study suggests otherwise. The therapy is high doses of interleukin-2, an immune system booster that can have nasty side effects, including seizures and abnormal heart rhythms. In a review of eight melanoma patients with tumors in their brains, this treatment doubled the average survival from 4 months to more than 8 months. The researchers call for extending use of this immunotherapy to melanoma patients with brain metastases.

Survival Patterns Following Brain Metastases for Patients with Melanoma in the Targeted Therapy Era

“Survival from metastatic melanoma (MM) has been significantly prolonged with the introduction of molecularly targeted therapy, including BRAF inhibitors (BRAFi) for patients (pts) with the V600E mutation. Here, we present the first data describing patterns of survival after diagnosis of brain metastases (BM) in a large cohort of these pts with long follow-up.”

Advances in Therapy for Melanoma Brain Metastases

Melanoma cells frequently metastasize to the brain, and approximately 50% of patients with metastatic melanoma develop intracranial disease. Historically, central nervous system dissemination has portended a very poor prognosis. Recent advances in systemic therapies for melanoma, supported by improved local therapy control of brain lesions, have resulted in better median survival for these patients. We review current local and systemic approaches for patients with melanoma brain metastases.”

Vemurafenib and radiation therapy in melanoma brain metastases

“Brain metastases in malignant melanoma carries a poor prognosis with minimal response to any therapy. The purpose of this pilot analysis was to find the effectiveness of vemurafenib, an oral BRAF inhibitor, and radiation therapy in V600 mutated melanoma with brain metastases. BRAF mutation status of the melanoma patients was determined by real-time PCR assay…”

Prognostic Factors for Overall Survival After Radiosurgery in Patients with Melanoma with Brain Mets

Brain metastases (BM) cause significant morbidity and mortality in patients with melanoma. This study identified serum LDH as an independent prognostic factor associated with overall survival. If this finding is confirmed in a prospective manner, the serum LDH level should be included in future prognostic algorithms for patients with melanoma and BM who are to receive stereotactic radiosurgery (SRS), according to the researchers.