ASCO GU 2022: Safety and Differential Clinical Activity of Nivolumab plus Ipilimumab in Patients with Non-Clear Cell RCC

( The 2022 GU ASCO Annual meeting included a renal cell carcinoma (RCC) session highlighting work from Dr. Omar Alhalabi and investigators presenting results assessing safety and differential clinical activity of nivolumab plus ipilimumab in patients with non-clear cell RCC. Pembrolizumab monotherapy recently showed promising efficacy in non-clear cell RCC, with an objective response rate (ORR) by histology of 28.8% for papillary RCC, 9.5% for chromophobe RCC, and 30.8% for unclassified RCC.1 However, combination immunotherapy data are limited in non-clear cell RCC.

This study retrospectively evaluated the efficacy and safety of nivolumab + ipilimumab in patients with non-clear cell RCC treated at the MD Anderson Cancer Center. ORR and progression-free survival (PFS) was determined using RECIST, and overall survival (OS) was measured from therapy start to death or last follow up.

Between November 2017 and July 2020, 27 patients with non-clear cell RCC were treated with nivolumab + ipilimumab at the MD Anderson Cancer Center, 25 patients (93%) received nivolumab + ipilimumab as first-line therapy, and 14 patients (52%) had prior nephrectomy. Histology subtypes included 13 (48%) papillary (4 with sarcomatoid features), 7 (26%) chromophobe (4 with sarcomatoid features), and 7 (26%) unclassified. Sites of metastases included lung in 52%, bone-in 37%, and liver in 22% of patients. IMDC risk was favorable (8%), intermediate (48%), and poor (44%). ORR in all patients was 30%: 7 patients achieved a partial response (PR), and 1 patient achieved a complete response (CR). ORR by histology subtype was 54% for papillary, 14% for chromophobe, and 0% for unclassified:

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Clinical benefit (defined as PR, CR, or stable disease [SD] for > 6 months) was achieved in 62% for papillary, 57% for chromophobe, and 29% for unclassified. At a median follow-up time of 17.1 months, for all 27 patients, median PFS was 7.2 months:

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Median OS was 18.5 months:

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Median OS per each variant histology subtype was not reached in papillary, 25.7 months in chromophobe, and 7.4 months in unclassified. Median PFS per variant histology subtype was 11.8 months in papillary, 4.0 months in chromophobe, and 2.8 months in unclassified. Seven patients (26%) developed Grade ≥3 toxicity: pneumonitis (n = 2), colitis (n = 2), hepatitis (n = 1), rash (n = 1), and immune-mediated glomerulonephritis (n = 1).

These results are consistent with previous reports showing favorable clinical efficacy for nivolumab + ipilimumab in papillary RCC, however unclassified and chromophobe RCC remain areas of need with limited treatment options:

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Dr. Alhalabi concluded his presentation of the safety and differential clinical activity of nivolumab plus ipilimumab in patients with non-clear cell RCC with the following concluding statements:

  • In this small retrospective study, nivolumab + ipilimumab was well-tolerated in patients with non-clear cell RCC and yielded high ORR and prolonged PFS in papillary RCC but disappointing efficacy results in chromophobe and unclassified RCC
  • Molecular studies are ongoing to understand the mechanisms of response and resistance to nivolumab + ipilimumab in these tumor subtypes

Presented by: Omar Alhalabi, MD, The University of Texas MD Anderson Cancer Center, Houston, TX

Co-Authors: Nathaniel Wilson, Helen Ajufo, Michael Lehner, Elshad Hasanov, Matthew T Campbell, Amishi Yogesh Shah, Jennifer Wang, Eric Jonasch, John C. Araujo, Jianbo Wang, Jianjun Gao, Sangeeta Goswami, Pavlos Msaouel, Nizar M. Tannir

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 17 – Saturday Feb 19, 2022 


  1. McDermott DF, Lee JL, Ziobro M, et al. Open-label, single-arm, phase II study of pembrolizumab monotherapy as first-line therapy in patients with advanced non-clear cell renal cell carcinoma. J Clin Oncol. 2021 Mar 20;39(9):1029-1039.