The impact of the time-of-day in the administration of immunotherapy and its efficacy in patients with advanced melanoma: A retrospective observational study

Background

Certain publications suggest that immunotherapy would be more effective if it were synchronised with the circadian oscillations of the immune system. We hypothesised that late treatment delivery in melanoma patients would correlate with worse survival outcomes.

Patients and methods

We conducted a monocentric retrospective study in patients with advanced cutaneous melanoma receiving immune checkpoint inhibitors as first-line therapy. We used the median clock time of all infusions (11:00) as the cut-off point to differentiate morning from afternoon. Patients were allocated to the morning or afternoon group depending on whether they had received >50% of their infusions before or after 11:00. A propensity score was calculated. Timing groups were assessed for association with overall and progression-free survival using a Cox proportional hazards model, survival curves were compared, and treatment-related adverse events (AEs) were analysed.

Results

We included 154 patients treated with frontline immunotherapy in a metastatic setting from 1 January 2013 to 1 January 2022, with a median age of 67 years (interquartile range: 56–75). Late treatment delivery was associated neither with worse overall survival (median not reached [34.9-not estimable] vs. 70.8 months; hazard ratio (HR) = 0.94 [0.63–1.39]) nor worse progression-free survival (22.3 vs. 26.5; HR = 0.99 [0.71–1.38]), and there were no differences in survival outcomes between the groups. Severe treatment-related AEs were significantly more frequent in the afternoon group than in the morning group (33 [34%] vs. 6 [11%] respectively, weighted p-value = 0.004).

Conclusion

Timing was not associated with worse efficacy outcomes, but morning administration appears to improve safety.