Baseline laboratory values and metastatic burden predict survival in addition to IMDC risk in real-world renal cell carcinoma patients treated with ipilimumab-nivolumab

Authors

  • Alaa Kheir Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Oncology, Akademiska University Hospital, Uppsala, Sweden https://orcid.org/0009-0000-0558-8622
  • Berglind Johannsdottir Department of Pelvic Cancer, Genitourinary Oncology, Karolinska University Hospital, Stockholm, Sweden; Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden
  • Alexandra Grönn-Weiss Department of Oncology, Karlstad Central Hospital, Karlstad, Sweden
  • Lisa L Liu Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden; Theme Cancer, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden
  • Anders Ullén Department of Pelvic Cancer, Genitourinary Oncology, Karolinska University Hospital, Stockholm, Sweden; Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden
  • Anna Laurell Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Oncology, Akademiska University Hospital, Uppsala, Sweden
  • Annika Håkansson Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Oncology, Akademiska University Hospital, Uppsala, Sweden
  • Ingrida Verbiené Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Oncology, Akademiska University Hospital, Uppsala, Sweden
  • Gustav Ullenhag Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Oncology, Akademiska University Hospital, Uppsala, Sweden https://orcid.org/0000-0003-4949-3267
  • Rickard Carlhed Department of Oncology, Karlstad Central Hospital, Karlstad, Sweden
  • Fernanda Costa Svedman Department of Pelvic Cancer, Genitourinary Oncology, Karolinska University Hospital, Stockholm, Sweden; Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden
  • Magnus Lindskog Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Pelvic Cancer, Genitourinary Oncology, Karolinska University Hospital, Stockholm, Sweden; Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden https://orcid.org/0000-0001-9484-1983
  • Ulrika Harmenberg Department of Pelvic Cancer, Genitourinary Oncology, Karolinska University Hospital, Stockholm, Sweden; Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden

DOI:

https://doi.org/10.2340/1651-226X.2025.44533

Keywords:

renal cell carcinoma, metastatic, immune checkpoint inhibitors, ipilimumab, nivolumab, biomarkers, survival rate

Abstract

Background and purpose: Clinical tools to optimally select real-world metastatic renal cell carcinoma (mRCC) patients for treatment with ipilimumab-nivolumab remain to be identified.

Patient and methods: Medical records of the first 100 mRCC patients treated with ipilimumab-nivolumab at three Swedish centers were retrospectively analyzed. Data on International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk, baseline levels of routine blood markers, and tumor burden were collected. Outcome variables were progression-free survival (PFS), overall survival (OS), and radiological response (RR) according to clinical routine imaging.

Results: At a median follow-up of 22 months, 65% had progressed or died with a median PFS of 7 months and an estimated median OS of 28 months. The RR rate was 45%, including 11% complete responses (CR). 29% had progressive disease as best response. IMDC poor-risk patients had shorter mPFS (4 vs 14 months; HR [hazard ratio] 1.90; P = 0.009), shorter mOS (12.5 months vs not reached; HR 4.27; P < 0.0001), and lower CR rate (3% vs 16%, P = 0.06) than IMDC intermediate/favorable patients. C-reactive protein (aHR 2.67; P = 0.040), albumin (aHR, 2.13; P = 0.039), neutrophil-lymphocyte-ratio (aHR, 2.8; P = 0.009), and > 2 metastatic sites (aHR, 2.13; P = 0.024) were associated with OS after adjusting for IMDC risk. Prior nephrectomy was not (aHR, 0.84; P = 0.62). A normal C-reactive protein was associated with an increased likelihood of CR (OR 7.2; P = 0.017).

Interpretation: Baseline blood markers and number of metastatic sites add prognostic value independently of IMDC risk in real-word mRCC patients treated with ipililmumab-nivolumab.

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2025-10-03

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Kheir, A., Johannsdottir, B., Grönn-Weiss, A., Liu, L. L., Ullén, A., Laurell, A., … Harmenberg, U. (2025). Baseline laboratory values and metastatic burden predict survival in addition to IMDC risk in real-world renal cell carcinoma patients treated with ipilimumab-nivolumab. Acta Oncologica, 64, 1355–1364. https://doi.org/10.2340/1651-226X.2025.44533

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Vol. 64 (2025): Acta Oncologica

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Copyright (c) 2025 Alaa Kheir, Berglind Johannsdottir, Alexandra Grönn-Weiss, Lisa L Liu, Anders Ullén, Anna Laurell, Annika Håkansson, Ingrida Verbiené, Gustav Ullenhag, Rickard Carlhed, Fernanda Costa Svedman, Magnus Lindskog, Ulrika Harmenberg

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