A Case Report of Severe Type B Lactic Acidosis Following First Dose of Nivolumab in a VHL-Mutated Metastatic Renal Cell Carcinoma

Overview

Journal Kidney Cancer

Date 2018 Oct 19

PMID 30334008

Citations 1

Authors

Erica Nakajima

Paul Leger

Ingrid A Mayer

Michael N Neuss

David D Chism

W Kimryn Rathmell

Affiliations

Soon will be listed here.

Abstract

We report a case of severe type B lactic acidosis (LA) in a 51-year-old male, 12 days after he received his first dose of nivolumab for metastatic Von Hippel Lindau (-mutated, clear cell renal cell carcinoma. Throughout his hospital course, infection, hypoperfusion, and tissue necrosis were not identified. We propose that his LA may have resulted from either inherent tumor glycolysis or immune activation and enhanced metabolism. The patient's course was complicated by acute renal failure, and his LA rose progressively, eventually necessitating daily hemodialysis (HD). After receiving five consecutive days of HD, the patient started everolimus daily with the intent of reducing glycolytic metabolism. Subsequently, the rate of lactic acid production slowed, and HD was no longer required after two doses of everolimus. To our knowledge, this is the first reported case of type B LA following nivolumab administration, and the use of everolimus to treat type B LA in a patient with renal cancer.

Citing Articles

Type B lactic acidosis: a rare oncological emergency.

Liu Q, Harji F, Jones A, Tarnower A BMJ Case Rep. 2020; 13(3).

PMID: 32234853 PMC: 7167422. DOI: 10.1136/bcr-2019-233068.

References

Borghaei H, Paz-Ares L, Horn L, Spigel D, Steins M, Ready N . Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015; 373(17):1627-39. PMC: 5705936. DOI: 10.1056/NEJMoa1507643. View

Nickerson M, Jaeger E, Shi Y, Durocher J, Mahurkar S, Zaridze D . Improved identification of von Hippel-Lindau gene alterations in clear cell renal tumors. Clin Cancer Res. 2008; 14(15):4726-34. PMC: 2629664. DOI: 10.1158/1078-0432.CCR-07-4921. View

Wieman H, Wofford J, Rathmell J . Cytokine stimulation promotes glucose uptake via phosphatidylinositol-3 kinase/Akt regulation of Glut1 activity and trafficking. Mol Biol Cell. 2007; 18(4):1437-46. PMC: 1838986. DOI: 10.1091/mbc.e06-07-0593. View

Nishino M, Sholl L, Hodi F, Hatabu H, Ramaiya N . Anti-PD-1-Related Pneumonitis during Cancer Immunotherapy. N Engl J Med. 2015; 373(3):288-90. PMC: 4539956. DOI: 10.1056/NEJMc1505197. View

Gibbons J, Abraham R, Yu K . Mammalian target of rapamycin: discovery of rapamycin reveals a signaling pathway important for normal and cancer cell growth. Semin Oncol. 2009; 36 Suppl 3:S3-S17. DOI: 10.1053/j.seminoncol.2009.10.011. View

Chen J, Appelbaum D, Kocherginsky M, Cowey C, Rathmell W, Mcdermott D . FDG-PET as a predictive biomarker for therapy with everolimus in metastatic renal cell cancer. Cancer Med. 2013; 2(4):545-52. PMC: 3799289. DOI: 10.1002/cam4.102. View

Chism D, Rathmell W . Seeing the forest for the trees: kidney oncogenomes in relation to therapeutic outcomes. Clin Cancer Res. 2014; 20(7):1721-3. PMC: 4077661. DOI: 10.1158/1078-0432.CCR-14-0056. View

Donnelly R, Finlay D . Glucose, glycolysis and lymphocyte responses. Mol Immunol. 2015; 68(2 Pt C):513-9. DOI: 10.1016/j.molimm.2015.07.034. View

Tanaka R, Fujisawa Y, Maruyama H, Nakamura Y, Yoshino K, Ohtsuka M . Nivolumab-induced thyroid dysfunction. Jpn J Clin Oncol. 2016; 46(6):575-9. DOI: 10.1093/jjco/hyw036. View

10.

de Groot R, Sprenger R, Imholz A, Gerding M . Type B lactic acidosis in solid malignancies. Neth J Med. 2011; 69(3):120-3. View

11.

Ansell S, Lesokhin A, Borrello I, Halwani A, Scott E, Gutierrez M . PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2014; 372(4):311-9. PMC: 4348009. DOI: 10.1056/NEJMoa1411087. View

12.

Motzer R, Escudier B, Mcdermott D, George S, Hammers H, Srinivas S . Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015; 373(19):1803-13. PMC: 5719487. DOI: 10.1056/NEJMoa1510665. View

13.

Gnarra J, Tory K, Weng Y, Schmidt L, Wei M, Li H . Mutations of the VHL tumour suppressor gene in renal carcinoma. Nat Genet. 1994; 7(1):85-90. DOI: 10.1038/ng0594-85. View

14.

Hudes G . Targeting mTOR in renal cell carcinoma. Cancer. 2009; 115(10 Suppl):2313-20. DOI: 10.1002/cncr.24239. View

15.

Kibel A, Iliopoulos O, DeCaprio J, Kaelin Jr W . Binding of the von Hippel-Lindau tumor suppressor protein to Elongin B and C. Science. 1995; 269(5229):1444-6. DOI: 10.1126/science.7660130. View

16.

Pause A, Lee S, Worrell R, Chen D, Burgess W, Linehan W . The von Hippel-Lindau tumor-suppressor gene product forms a stable complex with human CUL-2, a member of the Cdc53 family of proteins. Proc Natl Acad Sci U S A. 1997; 94(6):2156-61. PMC: 20057. DOI: 10.1073/pnas.94.6.2156. View

17.

Vandiver J, Singer Z, Harshberger C . Severe Hyponatremia and Immune Nephritis Following an Initial Infusion of Nivolumab. Target Oncol. 2016; 11(4):553-6. DOI: 10.1007/s11523-016-0426-9. View

18.

Duan D, Pause A, Burgess W, Aso T, Chen D, Garrett K . Inhibition of transcription elongation by the VHL tumor suppressor protein. Science. 1995; 269(5229):1402-6. DOI: 10.1126/science.7660122. View

19.

Hakimi A, Ostrovnaya I, Reva B, Schultz N, Chen Y, Gonen M . Adverse outcomes in clear cell renal cell carcinoma with mutations of 3p21 epigenetic regulators BAP1 and SETD2: a report by MSKCC and the KIRC TCGA research network. Clin Cancer Res. 2013; 19(12):3259-67. PMC: 3708609. DOI: 10.1158/1078-0432.CCR-12-3886. View

20.

Linehan W, Srinivasan R, Schmidt L . The genetic basis of kidney cancer: a metabolic disease. Nat Rev Urol. 2010; 7(5):277-85. PMC: 2929006. DOI: 10.1038/nrurol.2010.47. View