Incidence and impact of pseudoprogression and mixed responses in metastatic renal cell carcinoma patients treated with ipilimumab/nivolumab: a retrospective analysis

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.