Clinical activity of ipilimumab plus nivolumab in patients with metastatic non-clear cell renal cell carcinoma

Abstract Introduction Ipilimumab plus nivolumab are approved for intermediate and poor risk metastatic renal cell carcinoma (mRCC) patients, but activity in patients with non-clear cell RCC remains unknown. Methods Patients from Cleveland Clinic and UT Southwestern who received ipilimumab plus nivolumab for metastatic non-clear cell RCC between October 2017 and May 2019 were retrospectively identified. Ipilimumab plus nivolumab were administered per CHECKMATE 214. Imaging was obtained at baseline and every 12 weeks. Baseline patient characteristics, objective response per RECIST version 1.1 and treatment-related adverse events (TRAEs) per CTCAE version 5.0 were analyzed. Results Eighteen patients were identified. The median age was 59 years (range, 32-81), 77.8% male and ECOG PS 0 (38%) or 1 (50%). Median duration of treatment was 2.4 (range, 0.7 -12.3) months. Non-clear cell histologies included 6 papillary, 5 chromophobe, 3 unclassified, 2 adenocarcinoma of renal origin, 1 translocation and 1 medullary. The majority had intermediate (66%) or poor (22%) IMDC risk. Best objective response included 6 (33.3%) PR and 3 (16.7 %) SD. Among PR patients, the median time to best response was 3.0 months and median duration of PR was 4.3 months. Median progression-free survival (PFS) was 7.1 months. All grade TRAEs were noted in 11 (61.1%) patients and included colitis (22%), hepatotoxicity (16%), rash (11%) and fatigue (11%). Eleven patients (61%) had TRAEs requiring high-dose glucocorticoids (> 40 mg of prednisone equivalent per day. Conclusions Ipilimumab plus nivolumab demonstrated objective responses and notable toxicity in patients with non-clear cell RCC.