Rapid remission of symptomatic brain metastases in melanoma by programmed-death-receptor-1 inhibition

Abstract

Although ∼40% of patients with metastatic melanoma develop brain metastases, the presence of brain metastases often precludes enrolment in clinical trials for advanced melanoma. However, the development of symptomatic brain metastases markedly increases mortality. The antiprogrammed-death-receptor-1 antibody pembrolizumab achieves extracranial metastases disease response rates of up to 50%. Here, we report the rapid and sustained response of symptomatic multifocal brain metastases in a melanoma ipilimumab-pretreated patient under pembrolizumab, combined with high-dose dexamethasone therapy during the induction phase of therapy. Complete remission has been maintained for over 1 year of follow-up and has correlated with the response rate observed in the extracranial metastases. Radiological disease response was identified during the first follow-up visit in the absence of adjuvant radiotherapy. This report highlights the need for further clinical studies to specifically address the therapeutic potential of antiprogrammed-death-receptor-1 monotherapy in the management of untreated brain metastases in melanoma.

History and current state of immunotherapy in glioma and brain metastasis

“…117,118 There were also warning signs that PD-1/PDL-1 inhibitors should be used with caution. In a case study of 32 patients with NSCLC treated with nivolumab, 12 (37%) had severe events, leading to treatment discontinuation (eight of whom had CNS metastasis).…”

“…Similar to other agents, early trials using PD-1 inhibitors did not include patients with active brain metastasis, however, there were encouraging case reports of response of brain metastasis from renal cell cancer and melanoma. 117,118 There were also warning signs that PD-1/PDL-1 inhibitors should be used with caution. In a case study of 32 patients with NSCLC treated with nivolumab, 12 (37%) had severe events, leading to treatment discontinuation (eight of whom had CNS metastasis).…”

Targeted Therapies for Melanoma Brain Metastases

“…No results from BM specific clinical trials, investigating the efficacy of nivolumab treatment in melanoma BM patients, are yet available. However, several case series indicate the safety and efficacy of nivolumab monotherapy [6, 37]. The currently recruiting clinical trials will provide a deeper and more profound insight in the value of immune checkpoint inhibitor therapy in melanoma BM patients (Table 2).…”