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Complete response of hereditary leiomyomatosis and renal cell cancer (HLRCC)-associated renal cell carcinoma to nivolumab and ipilimumab combination immunotherapy by: a case report

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Abstract

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant disorder that results from a germline mutation in the fumarate hydratase gene (FH). Individuals with FH mutations are at risk of developing renal cell carcinoma (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) have aggressive clinical courses, but there is as yet no standardized therapy for advanced HLRCC-RCC. We report an aggressive RCC case in a 49-year-old man. Nine weeks after undergoing a total nephroureterectomy of the right kidney, he had a metastasectomy at port site. Within 14 weeks of the initial surgery, multiple recurrent tumors developed in the right retroperitoneal space. The pathological diagnosis was FH-deficient RCC. Genetic testing identified a heterozygous germline mutation of FH (c.641_642delTA), which confirmed the diagnosis of HLRCC-RCC. He received combination therapy with the immune checkpoint inhibitors (ICIs) nivolumab and ipilimumab as the first-line therapy. After 31 weeks of ICI treatment, a complete response was achieved. The disease-free condition has been prolonged for 24 months since the initial surgical treatment. This is the first case report of successful treatment of HLRCC-RCC with nivolumab plus ipilimumab. This combination immunotherapy is expected to be an effective approach to treat patients with advanced-stage HLRCC-RCC.

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Fig. 1
Fig. 2

Abbreviations

ccRCC:

Clear cell renal cell carcinoma

CR:

Complete response

CT:

Computed tomography

CTLA-4:

Cytotoxic T-lymphocyte-associated antigen-4

FH:

Fumarate hydratase

HLRCC:

Hereditary leiomyomatosis and renal cell cancer

ORR:

Objective response rates

OS:

Overall survival

RCC:

Renal cell carcinoma

ICI:

Immune checkpoint inhibitors

IMDC:

International Metastatic Renal Cell Carcinoma Database Consortium

PD-1:

Programmed death-1

PD-L1:

Programmed death-ligand 1

TIL:

Tumor infiltrating lymphocyte

TKI:

Tyrosine kinase inhibitor

TUR:

Transurethral resection

VEGF:

Vascular endothelial growth factor

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Acknowledgements

The authors thank Ms. Soeda H and Mr. T. Akagi for excellent assistance. This work was supported by JSPS KAKENHI Grant-in-Aid for Scientific Research: Grant Numbers 17K08745 and 20K07395 (M.F.), 17K11162 (Y.N.), 19K09694 (H.H.), 19K09717 (M.Y.) and 19K09676 (N.N.).

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Authors and Affiliations

  1. Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan

    Yasuhiro Iribe, Masato Yasui, Hisashi Hasumi, Narihiko Hayashi, Kazuhide Makiyama, Keiichi Kondo, Masahiro Yao & Noboru Nakaigawa

  2. Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan

    Mitsuko Furuya

  3. Department of Urology, Yokohama Municipal Citizen’s Hospital, Yokohama, Kanagawa, Japan

    Yousuke Shibata, Makoto Funahashi & Junichi Ota

  4. Department of Pathology, Yokohama Municipal Citizen’s Hospital, Yokohama, Kanagawa, Japan

    Hiromichi Iwashita

  5. Department of Surgical Pathology, Tokyo Women’s Medical University, Tokyo, Japan

    Yoji Nagashima

  6. Medical Mycology Research Center, Chiba University, Chiba, Japan

    Reiko Tanaka

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  1. Yasuhiro Iribe
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  2. Mitsuko Furuya
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Iribe, Y., Furuya, M., Shibata, Y. et al. Complete response of hereditary leiomyomatosis and renal cell cancer (HLRCC)-associated renal cell carcinoma to nivolumab and ipilimumab combination immunotherapy by: a case report. Familial Cancer 20, 75–80 (2021). https://doi.org/10.1007/s10689-020-00195-0

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