Immune checkpoint inhibitors can elicit atypical responses such as pseudoprogression (psPD) and mixed responses (MR). We aimed to analyze the occurrence and prognostic impact of atypical responses in metastatic clear-cell renal cell carcinoma (m-ccRCC) patients treated with ipilimumab/nivolumab.
In this retrospective series of m-ccRCC patients treated with ipilimumab/nivolumab in first-line, we performed radiographic evaluation using Response Evaluation Criteria in Solid Tumors and iRECIST consensus guidelines and compared both methods.
We assessed 258 baseline target lesions in 100 eligible patients. MR occurred in 24% of patients. In 15 patients (62%), the MR evolved to confirmed progressive disease (cPD), while in nine patients (38%), the MR evolved toward a partial response (PR) and was thus a psPD. psPD occurred in 13% of patients: with increase of all lesions in four patients or with MR features in nine patients. psPD patients had the second best time-to-progression (TTP) and cancer-specific survival (CSS), slightly lower compared to TTP and CSS in patients with PR without a phase of psPD and better than TTP and CSS in patients with stable disease as best response. From all patients who presented with PD at first CT evaluation (n = 40), including 17 patients with unconfirmed progressive disease and 23 patients with MR, in 12 (30%) patients this was a psPD and led to a PR.
Atypical responses such as psPD and MR occurred in 13 and 24% of m-ccRCC patients treated with ipilimumab/nivolumab. Patients with psPD had favorable outcomes, while MR in most cases evolved to progression.
Acta oncologica (Stockholm, Sweden). 2026 May 06*** epublish ***
Aaron Caeyman, Giulia Mammone, Lisa Kinget, Marcella Baldewijns, Liesbeth De Wever, Maarten Albersen, Philip R Debruyne, Octavie Demeulenaere, Edward Scott McTaggart, Saurabh Saraswat, Charlien Berghen, Gert De Meerleer, Stefan Naulaerts, Abhishek D Garg, Benoit Beuselinck
Department of General Medical Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium., Department of Pathology, University Hospitals Leuven, Leuven, Belgium., Department of Radiology, University Hospitals Leuven, Leuven, Belgium., Department of Urology, University Hospitals Leuven, Leuven, Belgium., Medical Oncology Department, Kortrijk Cancer Centre, az groeninge, Kortrijk, Belgium; Medical Technology Research Centre (MTRC), School of Life Sciences, Anglia Ruskin University, Cambridge, UK; School of Nursing & Midwifery, University of Plymouth, Plymouth, UK., Laboratory of Cell Stress & Immunity (CSI), Department of Cellular & Molecular Medicine, KU Leuven, Leuven, Belgium., Department of Radiotherapy/Oncology, University Hospitals Leuven, Leuven, Belgium., Department of General Medical Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium. .