Повторное применение ингибиторов контрольных точек иммунного ответа у пациентов с метастатической меланомой кожи: обзор литературы и клинический пример

Abstract

The prognosis of patients with metastatic and/or unresectable melanoma has changed dramatically over the past decade. When using modern medications (immune checkpoint inhibitors and BRAF/MEK inhibitors), more than 50% of patients survive 6.5 years. The use of immune checkpoint inhibitors (anti-PD-1 monotherapy) as the first line of therapy reduces the risk of progression or death by 60% (5-year progression-free survival in the nivolumab group was 28%, and in the dacarbazine group 3%, OR 0.4, 95% CI: 0.33–0.54; p = 0.0001) in the CheckMate 066 study. Despite the high results of anti-PD-1 monotherapy and overall survival, approximately 15–20% of patients with a complete response to aPD1 monotherapy and up to 35–40% of patients with a partial response to aPD1 monotherapy developed disease progression after 3–7 years. If there is an activating mutation in the BRAF gene, patients can be prescribed effective therapy with BRAF and MEK inhibitors, which will support at least half of them for at least 12 months. In another part of patients, immunotherapy may be interrupted at an earlier date (usually even before the antitumor effect is assessed) due to the development of adverse events. And such patients can also benefit from combined targeted therapy and in about half of the cases, in the same time frame (about 12 months), they will again find themselves in the situation of choosing the next line of therapy.