Immunotherapy in metastatic sarcomatoid renal cell carcinoma: A single institution experience

INTRODUCTION: Immune checkpoint inhibitors (CPIs) were recently approved in advanced clear cell renal cell carcinoma (RCC) and could be a promising option for metastatic RCC with sarcomatoid differentiation (sRCC) which otherwise carry a poor prognosis. We sought to compare outcomes between patients who received immunotherapy (IO) including CPIs or high dose interleukin-2 (HD IL2) for metastatic sRCC versus those who did not. PATIENTS AND METHODS: We performed a single-center retrospective data analysis of 44 consecutive sRCC patients with any percentage of sarcomatoid differentiation from our institutional RCC database of whom 34 received IO and 10 patients did not. RESULTS: Baseline variables between the two groups were not significantly different except for a greater percentage of patients with ≥40% sarcomatoid differentiation in the non-IO cohort. At a median follow-up of 27.6 months, patients treated with IO had a median overall survival of 57.6 months compared to 6.6 months in patients not treated with IO (p = 0.0002). Overall response rates (ORR) between the IO and non-IO group were 35.3% and 0% respectively (p = 0.06). When IO was given in the 1st line setting, the ORR was 25.0%, as compared to 44.4% in the 2nd line setting and beyond though limitations of small sample sizes apply. Immune-related adverse events (IRAE) occurred in 38.2% of patients in the IO group, with grade 3 events (mostly gastrointestinal) in 20.6% with no grade 4 or 5 events. IRAEs led to interruption or discontinuation of immunotherapy in 26.5%. CONCLUSION: Our results support IO as an effective therapeutic option for patients with metastatic sarcomatoid RCC. Further study of various IO regimens, including those affecting the interleukin-2 signaling pathway, and their efficacy in neoadjuvant and adjuvant settings are warranted in sRCC.