Abstract 100P
Background
Immunotherapy is currently the standard of care in the treatment of metastatic melanoma. Immune cells in the tumor microenvironment play a decisive role in tumor growth and response to therapy. NK and dendritic cells, monocytes, T and B lymphocytes exhibit circadian oscillations in the peripheral blood, as well as PD-L1 expression. Recent data from MEMOIR study suggests the effectiveness of immune checkpoint inhibitors in melanoma is lower when more than 20% of infusions are in the late afternoon.
Methods
Retrospective, unicentric, cohort study of stage IV melanoma patients under immunotherapy (ipilimumab, nivolumab or pembrolizumab) with PS 0-1, followed at our center between July 2016 and March 2022. Infusion times were obtained and dichotomized as morning (8am-2pm) or afternoon (2pm-8pm). Time to event outcomes were calculated using the Kaplan Meier method and tested using Cox regression model, using a 95% confidence interval (IC). Objective: To determine the impact of immunotherapy administration timing on the overall survival (OS) of patients with metastatic melanoma.
Results
In this time period, 73 patients were treated, and 37.0% of patients had at least three fourths (75%) of the immunotherapy infusions in the afternoon period. The median OS of the population was 24.2 months [CI 95%, 9.04 to 39.8), with a median follow-up time of 15.3 months. No significant demographic or tumor burden differences were found between the morning and afternoon groups. Having more than 75% of immunotherapy infusions in the afternoon results in a shorter median OS (13.8 vs 38.1 months; HR 1.94 [CI 95% 1.01 to 3.74]; p<0,01).
Conclusions
This study suggests that increasing the number of treatments in the afternoon period worsens the outcome of metastatic melanoma patients. Chrono-immunotherapy is a developing topic and could lead to higher survival rates in metastatic melanoma. Prospective randomized studies on immunotherapy timing should be performed.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A.R. Teixeira Sousa: Financial Interests, Personal, Invited Speaker: Roche, Merck Sharp & Dome, Novartis, Pierre-Fabre, Bristol-Myers Squibb, AstraZeneca, Glaxosmith, Lilly, Pfizer, Tesaro. A.B. Mansinho: Financial Interests, Personal, Invited Speaker: Amgen, Astellas, Bayer, BBraun, Bristol Myers-Squibb, Janssen, Merck-Serono, Merck Sharp & Dohme, Novartis, OMPharma, Pfizer, Pierre Fabre, Roche, Servier; Financial Interests, Personal and Institutional, Funding: Bayer, BBraun. All other authors have declared no conflicts of interest.