Efficacy of ipilimumab after anti-PD-1 therapy in sequential treatment of metastatic melanoma patients - Real world evidence

Adv Med Sci. 2020 Sep;65(2):316-323. doi: 10.1016/j.advms.2020.05.005. Epub 2020 Jun 15.

Abstract

Purpose: Immunotherapy has become a standard treatment option for patients with metastatic melanoma, and the use of checkpoint inhibitors significantly improves the treatment outcomes in this group.

Patients and methods: A total of 116 patients with metastatic melanoma were enrolled in the study. In the first line, they were treated with an anti-PD-1 inhibitor (nivolumab or pembrolizumab), following which ipilimumab was used as the second-line therapy.

Results: BRAF mutation was detected in 12 patients (10%). The median progression-free survival (PFS) of ipilimumab treatment was 2.8 months, the overall survival (OS) was 5.1 months. The rate of 6-month survival was 45%, 1-year survival was 24%, and 2-year survival was 3%. The responses to treatment were: complete response in 2 cases (2%), partial response in 7 cases (6%), stable disease in 39 cases (34%). In multivariate analysis, normal levels of lactate dehydrogenase (LDH) were associated with a longer median OS and PFS (p = 0.02 and p = 0.009, respectively), while 2 or less number of metastatic locations and the presence of BRAF mutations were correlated with a longer OS (p = 0.041 and p = 0.024, respectively).

Conclusions: Ipilimumab could be considered after anti-PD-1 treatment. Treatment with ipilimumab following anti-PD-1 therapy showed beneficial effects in patients with normal levels of LDH, 2 or less number of metastatic locations, and BRAF-mutated melanoma. However, further studies are required to confirm our results as the study included a low number of patients with BRAF mutation-positive melanoma. No significant increase in toxicity was detected with the use of ipilimumab after anti-PD-1 therapy.

Keywords: Anti-PD-1; Immunotherapy; Ipilimumab; Metastatic melanoma; Sequential treatment.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / secondary
  • Female
  • Follow-Up Studies
  • Humans
  • Ipilimumab / administration & dosage
  • Male
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Middle Aged
  • Nivolumab / administration & dosage
  • Prognosis
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Retrospective Studies
  • Survival Rate

Substances

  • Antibodies, Monoclonal, Humanized
  • Ipilimumab
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab
  • pembrolizumab