Immunotherapy treatment adverse events in patients with metastatic melanoma reveals positive correlation with better treatment outcome

Abstract

Introduction: Immunotherapy with CTLA-4 inhibitors and PD1 checkpoint inhibitors has been turnover in the treatment and prognosis of the patients with metastatic melanoma. From the expected survival of less than 12 months, the survival of these patients has increased to forty months and more. However, the immunotherapy either with anti-CTLA-4 antibody or with PD1 inhibitors or as a combination of both, has a broad pallet of significant immune related adverse events. Our study was performed in order to assess the correlation of the immune related adverse events and the treatment outcome defined with significant difference in the overall response rate (ORR) and progression free survival (PFS) for the patients that developed immune related adverse events through the immunotherapy treatment.

Method: The retrospective analysis of patients with metastatic melanoma treated with immunotherapy in 2020 at the Oncology Institute of Ljubljana was perform with an aim to evaluate the correlation between the immune related adverse events and the treatment outcome. In this study were included only patients with radiological evaluations of the immunotherapy treatment response. The patients were divided into two cohorts, the cohort of patients with immune related adverse events (irAE group) and cohort of patients with no immune related adverse events (NirAE). The overall response and progression free survival to be significantly better in the iSE cohort define the primary point of our study.To investigate the differences of the progression free survival in the irAE cohort and NirAE cohort we used survival analysis.

Results: Out of 120 patients treated with immunotherapy, the radiological response evaluation was performed for 99 patients, 61 patients in the NirAE cohort and 38 patients in irAE cohort. The ORR for the irAE and NirAE cohorts was 57% and 37% respectively. The PFS was significantly better for irAE cohort with 301.6 days compared to 247.29 days in the NirAE cohort. Results from the survival regression analysis showed significant increased survival probability from less than 60% for NirAE cohort to almost 80% for irAE cohort.

Conclusion: Patients with metastatic melanoma treated with immunotherapy that develop immune related adverse events have a better treatment outcome with a longer time to disease progression and better overall response compared to patients treated with immunotherapy without immune related adverse events.