Ribociclib plus letrozole alters the blood immune profile in older patients with HR+/HER2- metastatic breast cancer


  • Yentl Lambrechts Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, Leuven, Belgium
  • Sigrid Hatse Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, Leuven, Belgium
  • Cindy Kenis Department of General Medical Oncology and Geriatric Medicine, University Hospitals Leuven, Leuven, Belgium - Department of Public Health and Primary Care, Academic Centre for Nursing and Midwifery, KU Leuven, Leuven, Belgium
  • Lore Decoster Department of Medical Oncology, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), Brussels, Belgium
  • Evandro de Azambuja Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B), Brussels, Belgium
  • Patrick Neven Multidisciplinary Breast Center, University Hospitals Leuven, Leuven, Belgium
  • Claire Quaghebeur Medical Oncology, UCLouvain, CHU Namur Site Sainte-Elisabeth, Namur, Belgium
  • Frank Cornelis Medical Oncology Department, King Albert II Cancer Institute, Cliniques Universitaires Saint-Luc and Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
  • Didier Verhoeven Department of Medical Oncology, AZ KLINA, Brasschaat, University of Antwerp, Antwerp, Belgium
  • Annelore Barbeaux Department of Medical Oncology, CHR Verviers East Belgium, Verviers, Belgium
  • Jeroen Mebis Department of Medical Oncology, Jessa Hospital, Hasselt, Belgium
  • Julie Van Dievel Department of General Medical Oncology and Hematology, Imelda hospital, Bonheiden, Belgium
  • Vincent Verschaeve Department of Medical Oncology, GHDC Grand Hôpital de Charleroi, Charleroi, Belgium
  • Lionel Duck Department of Oncology, Clinique Saint-Pierre, Ottignies, Belgium
  • Eveline De Cuypere Department of Medical Oncology, AZ Sint-Jan Hospital Bruges, Bruges, Belgium
  • Giuseppe Floris Laboratory for Cell and Tissue Translational Research, Department of Imaging and Radiology, KU-Leuven - Department of Pathology, University Hospitals Leuven, Leuven, Belgium
  • Christine Desmedt Laboratory for Translational Breast Cancer Research, Department of Oncology, KU Leuven, Leuven, Belgium
  • Annouschka Laenen Leuven Biostatistics and Statistical Bioinformatics Center, KU Leuven, Leuven, Belgium
  • Noam Pondé Department of Medical Oncology, A.C. Camargo Cancer Center, São Paulo, SP, Brazil
  • Hans Wildiers Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, Leuven, Belgium; Multidisciplinary Breast Center, University Hospitals Leuven, Leuven, Belgium; Medical Oncology, UCLouvain, CHU Namur Site Sainte-Elisabeth, Namur, Belgium




breast cancer, biomarkers, immunity, translational research, Geriatric oncology


Background – The combination of CDK4/6 inhibitors and endocrine therapy (ET) is a standard firstline therapy for hormone receptor positive (HR+)/HER2- metastatic breast cancer (mBC). Preliminary data suggest that CDK4/6 inhibitors can alter the host immune function and stimulate tumor cell-directed immunity. However, clinical data are scarce, and no data exist about the impact of age and frailty on this phenomenon. Material and methods – This biomarker substudy of the RibOB trial (NCT03956654) evaluated the impact of ribociclib and letrozole on circulating immune cell subsets and protein markers in older ( ≥ 70 years) patients with HR+/HER2- mBC. Peripheral blood mononuclear cell subtyping and analysis of plasma immune response and checkpoint markers were performed using flow cytometry at baseline and after three months of ribociclib + ET. Frailty status was assessed at baseline using G8 score. Results – 20 patients (median age: 76 years, range: 70–87 years), 8 considered fit (G8>14), and 12 frail (G8 ≤ 14), were included. After three months of treatment, the immune subset composition showed significant increases in naïve B-, T-regulatory (Tregs), and CD4+ T-cells, while memory B-cells and Tregs were significantly decreased. In addition, consistent upregulation was seen in costimulatory receptors CD27 and CD28. Plasma immune checkpoint markers B7.2 (CD86) and PD-1 were significantly decreased. The immune subset profiles of fit versus frail persons showed no statistically significant difference. Conclusions – The study shows that the combination of ribociclib and ET modulates the immune system in older patients, potentially reversing the age-related immunosenescence process by increasing naïve T-cell and B-cell populations and decreasing memory populations.


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