Impact of Blood Type and Administration Timing on Therapeutic Outcomes of Immune Checkpoint Inhibitors for Patients with Lung Cancer in the Chinese Alpine Region

Background: Although immune function and tumor biology follow circadian rhythms, it is unclear whether optimizing the timing of immunotherapy can enhance clinical outcomes. This study evaluated the association between time-of-day administration of immune checkpoint inhibitors (ICIs) and treatment efficacy, and explored whether blood type modifies ICI response in Chinese lung cancer patients living in an alpine region. Methods: We performed a retrospective analysis of 1247 Chinese lung cancer patients treated with first-line chemoimmunotherapy between January 2016 and March 2021 at Harbin Medical University Cancer Hospital (Cohort 1, n = 839) and the Fourth Affiliated Hospital of Harbin Medical University (Cohort 2, n = 408). Primary endpoints were overall survival (OS) and progression-free survival (PFS) estimated by the Kaplan–Meier method. Secondary endpoints included immune-related adverse events (irAEs), disease control rate (DCR), and objective response rate (ORR). Results: Patients treated before 13:00 had superior outcomes compared with those treated later, with longer mOS (34.3 vs. 22.0 months, p < 0.0001) and mPFS (16.7 vs. 12.7 months, p < 0.001). The ORR was significantly higher in the before 13:00 group of Cohort 1 (64.4% vs. 55%, p = 0.005). Additionally, blood type O was associated with a higher irAEs rate (35.6% vs. 20.1%, p < 0.01) and longer mOS (34.5 vs. 23.1 months, p < 0.0001) than non-O types. Conclusions: Time-of-day administration and blood type may influence ICI efficacy, supporting circadian-informed and patient-tailored immunotherapy. These findings support incorporating circadian timing and patient-specific factors into cancer immunotherapy strategies.