Circulating cytokines and angiogenic factors have been associated with clinical outcomes in patients with metastatic renal cell carcinoma (RCC) receiving systemic therapy. However, none have yet examined cytokine concentrations in parallel cohorts receiving either immunotherapy or targeted therapy.
In this prospective correlative study, we enrolled 56 patients who were planned for treatment with either a vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI) or immune checkpoint inhibitor (ICI). Eligibility requirements permitted any RCC histologic subtype, International Metastatic Renal Cell Carcinoma risk classification, and line of therapy. Immunologic profile was assessed at baseline and after 1 month on treatment using a Human Cytokine 30-plex protein assay (Invitrogen). Clinical benefit was defined as complete response, partial response, or stable disease ≥6 months per RECIST (Response Evaluation Criteria in Solid Tumors) V.1.1 criteria.
Clinical benefit was similar between VEGF-TKI and ICI arms (65% vs 54%). Patients with clinical benefit from VEGF-TKIs had lower pretreatment levels of interleukin-6 (IL-6) (p=0.02), IL-1RA (p=0.03), and granulocyte colony-stimulating factor (CSF) (p=0.02). At 1 month, patients with clinical benefit from ICIs had higher levels of interferon-γ (IFN-γ) (p=0.04) and IL-12 (p=0.03). Among patients on VEGF-TKIs, those with clinical benefit had lower 1 month IL-13 (p=0.02) and granulocyte macrophage CSF (p=0.01) as well as higher 1 month VEGF (p=0.04) compared with patients with no clinical benefit.
For patients receiving VEGF-TKI or ICI therapy, distinct plasma cytokines were associated with clinical benefit. Our findings support additional investigation into plasma cytokines as biomarkers in metastatic RCC.
Journal for immunotherapy of cancer. 2021 Mar [Epub]
Alexander Chehrazi-Raffle, Luis Meza, Marice Alcantara, Nazli Dizman, Paulo Bergerot, Nicholas Salgia, JoAnn Hsu, Nora Ruel, Sabrina Salgia, Jasnoor Malhotra, Ewa Karczewska, Marcin Kortylewski, Sumanta Pal
Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California, USA., Department of Immuno-Oncology, City of Hope Comprehensive Cancer Center, Duarte, California, USA., Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA., Department of Medical Oncology, Cettro Cancer Center, Brasilia, Brazil., Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York, Brazil., Department of Computational and Quantitative Medicine, City of Hope Comprehensive Cancer Center, Duarte, California, USA., Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California, USA .