Oncolytic virotherapy, alone or in combination with immune checkpoint inhibitors, for advanced melanoma: A systematic review and meta-analysis

Int Immunopharmacol. 2020 Jan:78:106050. doi: 10.1016/j.intimp.2019.106050. Epub 2019 Dec 5.

Abstract

Background: Advanced melanoma, one of the most lethal forms of skin cancer, remains a difficult condition to treat, despite the substantial scientific progression in cancer treatment. Oncolytic virotherapy (OV), either alone or combined with immune checkpoint inhibitors (ICIs), has often been administrated in an attempt to cure this malignancy. However, the clinical outcomes dramatically vary among different reports.

Methods: In this study, we performed a meta-analysis to evaluate the clinical efficacy and safety profile of OV, combined with ICIs in some cases, in advanced melanoma patients. The original clinical studies were identified based on the online query in PubMed, Cochrane, and Web of Science before December 30, 2018.

Results: A total of 18 publications involving 1472 patients were included for the final meta-analysis. The data concerning objective response rate (ORR) and incidence rate of severe immune-related adverse events (irAEs) were extracted accordingly from the text or supplementary materials. The results illustrated that a single treatment of OV could generate a 25% ORR for advanced melanoma, and the ORR could be improved to 45% if combined with ICIs. Further analysis demonstrated that the introduction of ICIs in OV could increase the incidence rate of severe irAEs (AE ≥ 3) from 12% to 39%. However, the rate attributed to OV remains at 12% in the combination group.

Conclusion: The clinical efficacy of OV can be significantly improved by ICIs even though more onerous burden will be exerted simultaneously on the safety profile.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents, Immunological / administration & dosage*
  • Antineoplastic Agents, Immunological / adverse effects
  • CTLA-4 Antigen / antagonists & inhibitors
  • CTLA-4 Antigen / immunology
  • Clinical Trials as Topic
  • Combined Modality Therapy / adverse effects
  • Combined Modality Therapy / methods
  • Drug-Related Side Effects and Adverse Reactions / diagnosis
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Drug-Related Side Effects and Adverse Reactions / immunology
  • Humans
  • Immunotherapy / adverse effects
  • Immunotherapy / methods*
  • Incidence
  • Ipilimumab / administration & dosage
  • Ipilimumab / adverse effects
  • Melanoma / immunology
  • Melanoma / pathology
  • Melanoma / therapy*
  • Oncolytic Virotherapy / adverse effects
  • Oncolytic Virotherapy / methods*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology
  • Severity of Illness Index
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ipilimumab
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • pembrolizumab