Complete response of hereditary leiomyomatosis and renal cell cancer (HLRCC)-associated renal cell carcinoma to nivolumab and ipilimumab combination immunotherapy by: a case report.
Antineoplastic Agents, Immunological
/ therapeutic use
Carcinoma, Renal Cell
/ diagnostic imaging
Germ-Line Mutation
Humans
Immune Checkpoint Inhibitors
/ therapeutic use
Ipilimumab
/ therapeutic use
Leiomyomatosis
/ diagnostic imaging
Male
Middle Aged
Neoplastic Syndromes, Hereditary
/ diagnostic imaging
Nivolumab
/ therapeutic use
Pedigree
Skin Neoplasms
/ diagnostic imaging
Tomography, X-Ray Computed
Uterine Neoplasms
/ diagnostic imaging
Hereditary leiomyomatosis and renal cell cancer (HLRCC)
Ipilimumab
Kidney cancer
Metastasis
Nivolumab
Journal
Familial cancer
ISSN: 1573-7292
Titre abrégé: Fam Cancer
Pays: Netherlands
ID NLM: 100898211
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
04
12
2019
accepted:
07
07
2020
pubmed:
16
7
2020
medline:
30
11
2021
entrez:
16
7
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32666341
doi: 10.1007/s10689-020-00195-0
pii: 10.1007/s10689-020-00195-0
doi:
Substances chimiques
Antineoplastic Agents, Immunological
0
Immune Checkpoint Inhibitors
0
Ipilimumab
0
Nivolumab
31YO63LBSN
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
75-80Références
Alam NA, Bevan S, Churchman M, Barclay E, Barker K, Jaeger EE, Nelson HM, Healy E, Pembroke AC, Friedmann PS, Dalziel K, Calonje E, Anderson J, August PJ, Davies MG, Felix R, Munro CS, Murdoch M, Rendall J, Kennedy S, Leigh IM, Kelsell DP, Tomlinson IP, Houlston RS (2001) Localization of a gene (MCUL1) for multiple cutaneous leiomyomata and uterine fibroids to chromosome 1q42.3-q43. Am J Hum Genet 68(5):1264–1269. https://doi.org/10.1086/320124
doi: 10.1086/320124
pubmed: 11283798
pmcid: 1226106
Kiuru M, Launonen V, Hietala M, Aittomaki K, Vierimaa O, Salovaara R, Arola J, Pukkala E, Sistonen P, Herva R, Aaltonen LA (2001) Familial cutaneous leiomyomatosis is a two-hit condition associated with renal cell cancer of characteristic histopathology. Am J Pathol 159(3):825–829. doi: https://doi.org/10.1016/S0002-9440(10)61757-9
doi: 10.1016/S0002-9440(10)61757-9
pubmed: 11549574
pmcid: 1850481
Launonen V, Vierimaa O, Kiuru M, Isola J, Roth S, Pukkala E, Sistonen P, Herva R, Aaltonen LA (2001) Inherited susceptibility to uterine leiomyomas and renal cell cancer. Proc Natl Acad Sci USA 98(6):3387–3392. https://doi.org/10.1073/pnas.051633798
doi: 10.1073/pnas.051633798
pubmed: 11248088
Tomlinson IP, Alam NA, Rowan AJ, Barclay E, Jaeger EE, Kelsell D, Leigh I, Gorman P, Lamlum H, Rahman S, Roylance RR, Olpin S, Bevan S, Barker K, Hearle N, Houlston RS, Kiuru M, Lehtonen R, Karhu A, Vilkki S, Laiho P, Eklund C, Vierimaa O, Aittomaki K, Hietala M, Sistonen P, Paetau A, Salovaara R, Herva R, Launonen V, Aaltonen LA, Multiple Leiomyoma C (2002) Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet 30(4):406–410. doi: https://doi.org/10.1038/ng849
doi: 10.1038/ng849
pubmed: 11865300
Menko FH, Maher ER, Schmidt LS, Middelton LA, Aittomaki K, Tomlinson I, Richard S, Linehan WM (2014) Hereditary leiomyomatosis and renal cell cancer (HLRCC): renal cancer risk, surveillance and treatment. Fam Cancer 13(4):637–644. https://doi.org/10.1007/s10689-014-9735-2
doi: 10.1007/s10689-014-9735-2
pubmed: 4574691
pmcid: 4574691
Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM (2016) The 2016 WHO classification of tumours of the urinary system and male genital organs-Part A: renal, penile, and testicular tumours. Eur Urol 70(1):93–105. https://doi.org/10.1016/j.eururo.2016.02.029
doi: 10.1016/j.eururo.2016.02.029
pubmed: 26935559
Muller M, Ferlicot S, Guillaud-Bataille M, Le Teuff G, Genestie C, Deveaux S, Slama A, Poulalhon N, Escudier B, Albiges L, Soufir N, Avril MF, Gardie B, Saldana C, Allory Y, Gimenez-Roqueplo AP, Bressac-de Paillerets B, Richard S, Benusiglio PR (2017) Reassessing the clinical spectrum associated with hereditary leiomyomatosis and renal cell carcinoma syndrome in French FH mutation carriers. Clin Genet 92(6):606–615. doi: https://doi.org/10.1111/cge.13014
doi: 10.1111/cge.13014
Chen YB, Brannon AR, Toubaji A, Dudas ME, Won HH, Al-Ahmadie HA, Fine SW, Gopalan A, Frizzell N, Voss MH, Russo P, Berger MF, Tickoo SK, Reuter VE (2014) Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cancer: recognition of the syndrome by pathologic features and the utility of detecting aberrant succination by immunohistochemistry. Am J Surg Pathol 38(5):627–637. doi: https://doi.org/10.1097/PAS.0000000000000163
doi: 10.1097/PAS.0000000000000163
pubmed: 3984629
pmcid: 3984629
Merino MJ, Torres-Cabala C, Pinto P, Linehan WM (2007) The morphologic spectrum of kidney tumors in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. Am J Surg Pathol 31(10):1578–1585. doi: https://doi.org/10.1097/PAS.0b013e31804375b8
doi: 10.1097/PAS.0b013e31804375b8
pubmed: 17895761
Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C, Eigl BJ, Ruether JD, Cheng T, North S, Venner P, Knox JJ, Chi KN, Kollmannsberger C, McDermott DF, Oh WK, Atkins MB, Bukowski RM, Rini BI, Choueiri TK (2009) Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 27(34):5794–5799. doi: https://doi.org/10.1200/JCO.2008.21.4809
doi: 10.1200/JCO.2008.21.4809
pubmed: 19826129
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247. doi: https://doi.org/10.1016/j.ejca.2008.10.026
doi: 10.1016/j.ejca.2008.10.026
pubmed: 19097774
pmcid: 19097774
Motzer RJ, Tannir NM, McDermott DF, Aren Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthelemy P, Porta C, George S, Powles T, Donskov F, Neiman V, Kollmannsberger CK, Salman P, Gurney H, Hawkins R, Ravaud A, Grimm MO, Bracarda S, Barrios CH, Tomita Y, Castellano D, Rini BI, Chen AC, Mekan S, McHenry MB, Wind-Rotolo M, Doan J, Sharma P, Hammers HJ, Escudier B, CheckMate I (2018) Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med 378(14):1277–1290. https://doi.org/10.1056/NEJMoa1712126
doi: 10.1056/NEJMoa1712126
pubmed: 29562145
pmcid: 5972549
Escudier B, Porta C, Schmidinger M, Rioux-Leclercq N, Bex A, Khoo V, Grunwald V, Gillessen S, Horwich A, Committee EG (2019) Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-updagger. Ann Oncol 30(5):706–720. https://doi.org/10.1093/annonc/mdz056
doi: 10.1093/annonc/mdz056
pubmed: 30788497
Ljungberg B, Albiges L, Abu-Ghanem Y, Bensalah K, Dabestani S, Fernandez-Pello S, Giles RH, Hofmann F, Hora M, Kuczyk MA, Kuusk T, Lam TB, Marconi L, Merseburger AS, Powles T, Staehler M, Tahbaz R, Volpe A, Bex A (2019) European Association of urology guidelines on renal cell carcinoma: the 2019 update. Eur Urol 75(5):799–810. https://doi.org/10.1016/j.eururo.2019.02.011
doi: 10.1016/j.eururo.2019.02.011
pubmed: 30803729
Armstrong AJ, Halabi S, Eisen T, Broderick S, Stadler WM, Jones RJ, Garcia JA, Vaishampayan UN, Picus J, Hawkins RE, Hainsworth JD, Kollmannsberger CK, Logan TF, Puzanov I, Pickering LM, Ryan CW, Protheroe A, Lusk CM, Oberg S, George DJ (2016) Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial. Lancet Oncol 17(3):378–388. doi: https://doi.org/10.1016/S1470-2045(15)00515-X
doi: 10.1016/S1470-2045(15)00515-X
pubmed: 26794930
pmcid: 6863151
Tannir NM, Jonasch E, Albiges L, Altinmakas E, Ng CS, Matin SF, Wang X, Qiao W, Dubauskas Lim Z, Tamboli P, Rao P, Sircar K, Karam JA, McDermott DF, Wood CG, Choueiri TK (2016) Everolimus versus sunitinib prospective evaluation in metastatic non-clear cell renal cell carcinoma (ESPN): a randomized multicenter phase 2 trial. Eur Urol 69(5):866–874. https://doi.org/10.1016/j.eururo.2015.10.049
doi: 10.1016/j.eururo.2015.10.049
pubmed: 26626617
Geynisman DM (2015) Anti-programmed cell death protein 1 (PD-1) antibody nivolumab leads to a dramatic and rapid response in papillary renal cell carcinoma with sarcomatoid and rhabdoid features. Eur Urol 68(5):912–914. https://doi.org/10.1016/j.eururo.2015.07.008
doi: 10.1016/j.eururo.2015.07.008
pubmed: 26194044
Ruiz-Banobre J, Anido U, Abdulkader I, Antunez-Lopez J, Lopez-Lopez R, Garcia-Gonzalez J (2016) Long-term response to nivolumab and acute renal failure in a patient with metastatic papillary renal cell carcinoma and a PD-L1 tumor expression increased with sunitinib therapy: a case report. Front Oncol 6:250. https://doi.org/10.3389/fonc.2016.00250
doi: 10.3389/fonc.2016.00250
pubmed: 27921007
pmcid: 5118772
Adrianzen Herrera DA, Fleisig SB, Gartrell BA (2017) Impressive and durable response to nivolumab in a patient with metastatic type 2 papillary renal cell carcinoma: on-label but without evidence. Invest New Drugs 35(5):665–668. https://doi.org/10.1007/s10637-017-0469-5
doi: 10.1007/s10637-017-0469-5
pubmed: 28466375
McDermott DF, Lee J-L, Ziobro M, Gafanov R, Matveev VB, Suarez C, Donskov F, Pouliot F, Alekseev BY, Wiechno PJ, Tomczak P, Duran MAC, Shin SJ, Silverman RK, Perini RF, Schloss C, Atkins MB (2019) First-line pembrolizumab (pembro) monotherapy for advanced non-clear cell renal cell carcinoma (nccRCC): results from KEYNOTE-427 cohort B. J Clin Oncol 37(7):1. https://doi.org/10.1200/JCO.2019.37.7_suppl.546
doi: 10.1200/JCO.2019.37.7_suppl.546
Rini BI, Battle D, Figlin RA, George DJ, Hammers H, Hutson T, Jonasch E, Joseph RW, McDermott DF, Motzer RJ, Pal SK, Pantuck AJ, Quinn DI, Seery V, Voss MH, Wood CG, Wood LS, Atkins MB (2019) The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of advanced renal cell carcinoma (RCC). J Immunother Cancer 7(1):354. doi: https://doi.org/10.1186/s40425-019-0813-8
doi: 10.1186/s40425-019-0813-8
pubmed: 31856918
pmcid: 6924043
Choi Y, Keam B, Kim M, Yoon S, Kim D, Choi JG, Seo JY, Park I, Lee JL (2019) Bevacizumab plus erlotinib combination therapy for advanced hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinoma: a multicenter retrospective analysis in korean patients. Cancer Res Treat 51(4):1549-1556. https://doi.org/10.4143/crt.2019.086
doi: 10.4143/crt.2019.086
Srinivasan R, Gurram S, Al Harthy M, Singer EA, Sidana A, Shuch BM, Ball MW, Friend JC, Mac L, Purcell E, Vocke C, Kong HH, Cowen EW, Choyke PL, Malayeri AA, Long L, Shih JH, Merino MJ, Linehan MW (2020) Results from a phase II study of bevacizumab and erlotinib in subjects with advanced hereditary leiomyomatosis and renal cell cancer (HLRCC) or sporadic papillary renal cell cancer. J Clin Oncol 38:5004 (15_suppl). https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.5004
Park I, Shim YS, Go H, Hong BS, Lee JL (2019) Long-term response of metastatic hereditary leiomyomatosis and renal cell carcinoma syndrome associated renal cell carcinoma to bevacizumab plus erlotinib after temsirolimus and axitinib treatment failures. BMC Urol 19(1):51. doi: https://doi.org/10.1186/s12894-019-0484-2
doi: 10.1186/s12894-019-0484-2
pubmed: 31182090
pmcid: 6558845
Alaghehbandan R, Stehlik J, Trpkov K, Magi-Galluzzi C, Condom Mundo E, Pane Foix M, Berney D, Sibony M, Suster S, Agaimy A, Montiel DP, Pivovarcikova K, Michalova K, Daum O, Ondic O, Rotterova P, Dusek M, Hora M, Michal M, Hes O (2017) Programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) expression in fumarate hydratase-deficient renal cell carcinoma. Ann Diagn Pathol 29:17–22. doi: https://doi.org/10.1016/j.anndiagpath.2017.04.007
doi: 10.1016/j.anndiagpath.2017.04.007
pubmed: 28807336
Teng MW, Ngiow SF, Ribas A, Smyth MJ (2015) Classifying cancers based on T-cell infiltration and PD-L1. Cancer Res 75(11):2139–2145. https://doi.org/10.1158/0008-5472.CAN-15-0255
doi: 10.1158/0008-5472.CAN-15-0255
pubmed: 25977340
pmcid: 4452411
Curran MA, Montalvo W, Yagita H, Allison JP (2010) PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci USA 107(9):4275–4280. https://doi.org/10.1073/pnas.0915174107
doi: 10.1073/pnas.0915174107
pubmed: 20160101
Das R, Verma R, Sznol M, Boddupalli CS, Gettinger SN, Kluger H, Callahan M, Wolchok JD, Halaban R, Dhodapkar MV, Dhodapkar KM (2015) Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo. J Immunol 194(3):950–959. doi: https://doi.org/10.4049/jimmunol.1401686
doi: 10.4049/jimmunol.1401686
pubmed: 25539810
McGregor BA, McKay RR, Braun DA, Werner L, Gray K, Flaifel A, Signoretti S, Hirsch MS, Steinharter JA, Bakouny Z, Flippot R, Wei XX, Choudhury A, Kilbridge K, Freeman GJ, Van Allen EM, Harshman LC, McDermott DF, Vaishampayan U, Choueiri TK (2020) Results of a multicenter phase II study of atezolizumab and bevacizumab for patients with metastatic renal cell carcinoma with variant histology and/or sarcomatoid features. J Clin Oncol 38(1):63–70. https://doi.org/10.1200/JCO.19.01882
doi: 10.1200/JCO.19.01882
pubmed: 31721643
Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, Pouliot F, Alekseev B, Soulieres D, Melichar B, Vynnychenko I, Kryzhanivska A, Bondarenko I, Azevedo SJ, Borchiellini D, Szczylik C, Markus M, McDermott RS, Bedke J, Tartas S, Chang YH, Tamada S, Shou Q, Perini RF, Chen M, Atkins MB, Powles T, Investigators K- (2019) Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 380(12):1116–1127. https://doi.org/10.1056/NEJMoa1816714
doi: 10.1056/NEJMoa1816714
pubmed: 30779529
Motzer RJ, Penkov K, Haanen J, Rini B, Albiges L, Campbell MT, Venugopal B, Kollmannsberger C, Negrier S, Uemura M, Lee JL, Vasiliev A, Miller WH Jr, Gurney H, Schmidinger M, Larkin J, Atkins MB, Bedke J, Alekseev B, Wang J, Mariani M, Robbins PB, Chudnovsky A, Fowst C, Hariharan S, Huang B, di Pietro A, Choueiri TK (2019) Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 380(12):1103–1115. https://doi.org/10.1056/NEJMoa1816047
doi: 10.1056/NEJMoa1816047
pubmed: 30779531
pmcid: 6716603