Mixed Response to Nivolumab Among Different Metastatic Sites in Patients With Metastatic Renal Cell Carcinoma: Incidence and Clinical Implications

Discordant responses to immune checkpoint inhibition (ICIs) may occur at different sites in metastatic renal cell carcinoma (mRCC). This study investigated the incidence and prognostic significance of mixed response in mRCC patients treated with nivolumab.

We retrospectively analyzed 116 mRCC patients who underwent nivolumab monotherapy without prior ICIs. The best overall response (BOR) was evaluated for each patient using RECIST version 1.1, and organ-specific responses were assessed for each metastatic site. Patients were classified into three groups: responders (lesion shrinkage in one or more metastatic organs without growth in any organ), non-responders (no lesion shrinkage in any organ), and mixed responders (co-existence of metastatic organ with shrinking lesions and those with growing lesions).

The median age was 68 years, and 74.1% of patients were male. The IMDC risk was favorable/intermediate/poor in 17/79/20 patients, respectively. BOR was CR/PR/SD/PD in 2/24/38/52 patients, respectively; objective response rate (ORR) was 22.4%. In organ-specific responses, ORR was lower for bone (7.1%), kidney (8.8%), and brain (0%) metastases than for other sites (17.4%-50.0%). The analysis classified 49 (42.2%), 15 (12.9%), and 52 (44.8%) patients as responders, mixed responders, and non-responders, respectively. During a median follow-up of 20.9 months, the median overall survival (OS) was 45.7 months. Two-year OS rate was 72.7% overall, and 92.2%, 90.0%, and 46.4% for responders, mixed responders, and non-responders, respectively (p < 0.001).

Nivolumab yielded diverse organ-specific responses, with 12.9% of patients exhibiting mixed response. Further studies are required to explore optimal management of mixed responders to immune checkpoint inhibition in mRCC.