Efficacy and safety of nivolumab plus ipilimumab in patients with metastatic variant histology (non-clear cell) renal cell carcinoma

• DOI: 10.1136/jitc-2024-010958
• Publication Date: 2025-02-12T18:20:25Z
• Authors: Mohammad Jad Moussa; Jaanki Khandelwal; Nathaniel R Wilson; Kiran L Malikayil; Devaki Shilpa Surasi; Tharakeswara K Ba...; Yiyun Lin; Priya Rao; Pheroze Tamboli; Kanishka Sircar; Helen Ajufo; Khaled M Elsayes; Amishi Shah; Andrew C Johns; Sangeeta Goswami; Elshad Hasanov; Eric Jonasch; Pavlos Msaouel; Matthew T Campbell; Omar Alhalabi; Nizar M Tannir
• Keywords: Chromophobe cell; Progression-free survival

Background Nivolumab plus ipilimumab (nivo/ipi) is a standard of care first-line (1 L) therapy for patients with metastatic clear-cell renal cell carcinoma (ccRCC), but its role in metastatic, non-ccRCC has not been fully defined. We report single-institution experience nivo/ipi non-ccRCC. Methods Between November 2017 and February 2024, 55 received at MD Anderson Cancer Center. The tumor response was assessed by blinded radiologists using RECIST v1.1. overall rate (ORR), progression-free survival (PFS), PFS milestone, duration (DoR), (OS) were determined. Next-generation sequencing (NGS) performed on available specimens. Results Twenty-five (45.5%) had papillary histology (pRCC), 12 (21.8%) chromophobe (chRCC), 18 (32.7%) unclassified RCC (uRCC). Fifty-two (94.5%) 1 L. Sarcomatoid features (SF) found 20 (36.4%) cases. ORR 48% (12/25) pRCC, 25% (3/12) chRCC (all 3 cases SF), 27.8% (5/18) uRCC, 55% (11/20) across histologies SF. median 10.6 months (95% CI: 2.8 to 22.8) 3.6 0.9 – NE) chRCC, 2.1 7) uRCC; 6-month milestone 56% 36.3 75.7), 41.7% 22 61.3), 38.9% 21.7 56.1) respectively. DoR the entire cohort 8.5 8 NE). OS 36.7 11.5 54.8) 25.7 11.1 6.5 uRCC. Ten (18.2%) discontinued treatment due treatment-related adverse events (AEs). Grade 3/4 immune-mediated AEs noted 17 (30.9%) patients. NGS 26 cases: TP53 (42%), PTEN (23%), TERT (23%) alterations most frequently found, mutations enriched pRCC Conclusion Nivo/ipi produced favorable outcomes supporting use as L therapy. Responses exclusively Despite achieving an nivo/ipi, uRCC short inferior OS.