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.
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.
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).
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.
The authors.
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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.