Recent studies have demonstrated that earlier time-of-day infusion of immune checkpoint inhibitors (ICIs) is associated with longer progression-free survival (PFS) and overall survival (OS) among patients with metastatic melanoma and non-small cell lung cancer. These data are in line with growing preclinical evidence that the adaptive immune response may be more effectively stimulated earlier in the day. We sought to determine the impact of time-of-day ICI infusions on outcomes among patients with metastatic renal cell carcinoma (mRCC).
The treatment records of all patients with stage IV RCC who began ICI therapy within a multicenter academic hospital system between 2015 and 2020 were reviewed. The associations between the proportion of ICI infusions administered prior to noon (denoting morning infusions) and PFS and OS were evaluated using univariate and multivariable Cox proportional hazards regression.
In this study, 201 patients with mRCC (28% women) received ICIs and were followed over a median of 18 months (IQR 5-30). The median age at the time of ICI initiation was 63 years (IQR 56-70). 101 patients (50%) received ≥20% of their ICI infusions prior to noon (Group A) and 100 patients (50%) received <20% of infusions prior to noon (Group B). Across the two comparison groups, initial ICI agents consisted of nivolumab (58%), nivolumab plus ipilimumab (34%), and pembrolizumab (8%). On univariate analysis, patients in Group A had longer PFS and OS compared with those in Group B (PFS HR 0.67, 95% CI 0.48 to 0.94, Punivar=0.020; OS HR 0.57, 95% CI 0.34 to 0.95, Punivar=0.033). These significant findings persisted following multivariable adjustment for age, sex, performance status, International Metastatic RCC Database Consortium risk score, pretreatment lactate dehydrogenase, histology, and presence of bone, brain, and liver metastases (PFS HR 0.70, 95% CI 0.50 to 0.98, Pmultivar=0.040; OS HR 0.57, 95% CI 0.33 to 0.98, Pmultivar=0.043).
Patients with mRCC may benefit from earlier time-of-day receipt of ICIs. Our findings are consistent with established mechanisms of chrono-immunology, as well as with preceding analogous studies in melanoma and lung cancer. Additional prospective randomized trials are warranted.
Journal for immunotherapy of cancer. 2024 Mar 26*** epublish ***
Jimmy S Patel, Yena Woo, Amber Draper, Caroline S Jansen, Jennifer W Carlisle, Pasquale F Innominato, Francis A Lévi, Layla Dhabaan, Viraj A Master, Mehmet A Bilen, Mohammad K Khan, Michael C Lowe, Haydn Kissick, Zachary S Buchwald, David C Qian
Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, Georgia, USA., University of Chicago Pritzker School of Medicine, Chicago, Illinois, USA., Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, Georgia, USA., Emory University School of Medicine, Atlanta, Georgia, USA., Cancer Research Centre, Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UK., Emory University, Atlanta, Georgia, USA., Department of Urology, Emory University School of Medicine, Atlanta, Georgia, USA., Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute of Emory University, Atlanta, Georgia, USA., Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, Georgia, USA .