Patients with advanced melanoma who receive less than 20% of their immune checkpoint inhibitor (ICI) infusions in the evening have superior overall survival (OS), according to a study published in The Lancet Oncology.

With the ongoing MEMOIR study, researchers are attempting to determine whether specific time-of-day patterns of ICI infusions might affect treatment efficacy in patients with advanced melanoma.

The researchers reported results in 299 adults with stage IV melanoma who were treated with 4001 infusions of ipilimumab, nivolumab, or pembrolizumab. Patients had a median age of 61 years, and 66% were men.


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The median follow-up was 27 months, and the primary outcome was OS. The researchers calculated the association between OS and the proportion of infusions received after 4:30 pm using Cox regression and propensity score matching.

Results showed that each additional 20% of ICI infusions received after 4:30 pm was associated with a crude OS hazard ratio (HR) of 1.31 (95% CI, 1.00-1.71; P =.046).

After propensity score matching, there were 73 patients who received 20% or more of their ICI infusions after 4:30 pm and 73 patients who received less than 20% of their ICI infusions after 4:30 pm.

In the matched analysis, receiving at least 20% of ICI infusions after 4:30 pm was significantly associated with shorter OS. The median OS was 4.8 years in this group and was not reached in patients who received less than 20% of their ICI infusions after 4:30 pm (HR, 2.04; 95% CI, 1.04-4.00; P =.038).

The 5-year OS rate was 49% in patients who received at least 20% of their infusions after 4:30 pm and was 68% in patients who received less than 20% of their infusions after that time. 

In multivariable analyses, receiving at least 20% of ICI infusions after 4:30 pm was significantly associated with shorter OS in both the matched cohort (HR, 2.16; 95% CI, 1.10-4.25; P =.025) and the full unmatched sample (HR, 1.80; 95% CI, 1.08-2.98; P =.023).

Adverse events (AEs) that led to treatment modifications or discontinuation were similar between the treatment groups. Overall, the most common AEs were colitis (18%), hepatitis (9%), and hypophysitis (5%). No treatment-related deaths occurred.

The researchers noted that this study was limited by its single-center and retrospective nature, the distribution of ICI infusion times across patients and for each patient, and variations in the sequence of infusions.

“In the absence of randomized evidence, the results presented here could be used to guide immunotherapy infusion scheduling with the goal of optimizing treatment response,” the researchers wrote.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Qian DC, Kleber T, Brammer B, et al. Effect of immunotherapy time-of-day infusion on overall survival among patients with advanced melanoma in the USA (MEMOIR): A propensity score-matched analysis of a single-centre, longitudinal study. Lancet Oncol. Published online November 12, 2021. doi:10.1016/S1470-2045(21)00546-5