Top

Published in:

01-02-2021 | Multiple Myeloma | Original Article

A new parameter in multiple myeloma: CYP3A4*1B single nucleotide polymorphism

Authors: Istemi Serin, Sacide Pehlivan, Ilknur Gundes, Yasemin Fidan Oyaci, Mustafa Pehlivan

Published in: Annals of Hematology | Issue 2/2021

Abstract

Multiple myeloma (MM) is a disease caused by malignant plasma cells, causing free light chain release accompanying the increase in monoclonal immunoglobulin. Cytochrome P450 (CYP) is one of the large and functional enzyme families composed of various hemoproteins. This protein network has been shown to play a role in many treatment steps in current practices. We aimed to investigate the relationship between genotypes of CYP3A4*1B and treatment response and prognosis of MM. Seventy-two patients diagnosed with MM between January 2016 and 2020 and 100 healthy people to create a control group participated in our study. Genotypes were classified in 3 separate groups as NN, MN, and MM. Both PFS and OS were significantly higher in the NN genotype (p = 0.001, p = 0.014). Being under the age of 65 was 27.988 times more protective for OS and 4.496 times for PFS (p = 0.006, p = 0.017). NN genotype was shown to be 41.666-fold protective for OS and 3.144-fold protective for PFS (p = 0.004, p = 0.030). This study demonstrated that CYP3A4*1B NN genotype, which is an important cytochrome p450 member for the treatment of MM, was 41.666-fold protective for OS and 3.144-fold protective for PFS. It was shown in this study for the first time in the literature as a valuable contribution.

Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV et al (2014) International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 15(12):e538–e548. https://doi.org/10.1016/S1470-2045(14)70442-5CrossRefPubMed

Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin. 69(1):7–34. https://doi.org/10.3322/caac.21551CrossRefPubMed

Palumbo A, Anderson K (2011) Multiple myeloma. N Engl J Med. 364(11):1046–1060. https://doi.org/10.1056/NEJMra1011442CrossRefPubMed

Kazandjian D (2016) Multiple myeloma epidemiology and survival: a unique malignancy. Semin Oncol. 43(6):676–681. https://doi.org/10.1053/j.seminoncol.2016.11.004CrossRefPubMedPubMedCentral

Alzahrani AM, Rajendran P (2020) The multifarious link between cytochrome P450s and cancer. Oxid Med Cell Longev. 2020:3028387. https://doi.org/10.1155/2020/3028387CrossRefPubMedPubMedCentral

Guengerich FP, Waterman MR, Egli M (2016) Recent structural insights into cytochrome P450 function. Trends Pharmacol Sci. 37(8):625–640. https://doi.org/10.1016/j.tips.2016.05.006CrossRefPubMed

Nelson DR, Koymans L, Kamataki T, Stegeman JJ, Feyereisen R, Waxman DJ, Waterman MR, Gotoh O, Coon MJ, Estabrook RW, Gunsalus IC, Nebert DW (1996) P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics. 6(1):1–42. https://doi.org/10.1097/00008571-199602000-00002CrossRefPubMed

Nelson DR, Zeldin DC, Hoffman SM, Maltais LJ, Wain HM, Nebert DW (2004) Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants. Pharmacogenetics 14(1):1–18CrossRef

Manikandan P, Nagini S (2018) Cytochrome P450 structure, function and clinical significance: a review. Curr Drug Targets. 19(1):38–54. https://doi.org/10.2174/1389450118666170125144557CrossRefPubMed

10.

Lolodi O, Wang YM, Wright WC, Chen T (2017) Differential regulation of CYP3A4 and CYP3A5 and its implication in drug discovery. Curr Drug Metab. 18(12):1095–1105. https://doi.org/10.2174/1389200218666170531112038CrossRefPubMedPubMedCentral

11.

Kacevska M, Ivanov M, Wyss A, Kasela S, Milani L, Rane A, Ingelman-Sundberg M (2012) DNA methylation dynamics in the hepatic CYP3A4 gene promoter. Biochimie. 94(11):2338–2344. https://doi.org/10.1016/j.biochi.2012.07.013CrossRefPubMed

12.

Kuehl P, Zhang J, Lin Y, Lamba J, Assem M, Schuetz J, Watkins PB, Daly A, Wrighton SA, Hall SD, Maurel P, Relling M, Brimer C, Yasuda K, Venkataramanan R, Strom S, Thummel K, Boguski MS, Schuetz E (2001) Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat Genet. 27(4):383–391. https://doi.org/10.1038/86882CrossRefPubMed

13.

Rebbeck TR, Jaffe JM, Walker AH, Wein AJ, Malkowicz SB (1998) Modification of clinical presentation of prostate tumors by a novel genetic variant in CYP3A4. J Natl Cancer Inst 90(16):1225–1229. https://doi.org/10.1093/jnci/90.16.1225 Erratum in: J Natl Cancer Inst 1999 Jun 16;91(12):1082CrossRefPubMed

14.

Klein K, Zanger UM (2013) Pharmacogenomics of cytochrome P450 3A4: recent progress toward the “missing heritability” problem. Front Genet. 4:12. https://doi.org/10.3389/fgene.2013.00012CrossRefPubMedPubMedCentral

15.

Paris PL, Kupelian PA, Hall JM, Williams TL, Levin H, Klein EA, Casey G, Witte JS (1999) Association between a CYP3A4 genetic variant and clinical presentation in African-American prostate cancer patients. Cancer Epidemiol Biomarkers Prev. 8(10):901–905PubMed

16.

Basseville A, Preisser L, de Carné Trécesson S et al (2011) Irinotecan induces steroid and xenobiotic receptor (SXR) signaling to detoxification pathway in colon cancer cells. Mol Cancer 10:80. https://doi.org/10.1186/1476-4598-10-80CrossRefPubMedPubMedCentral

17.

Luckert C, Ehlers A, Buhrke T, Seidel A, Lampen A, Hessel S (2013) Polycyclic aromatic hydrocarbons stimulate human CYP3A4 promoter activity via PXR. Toxicol Lett 222(2):180–188CrossRef

18.

Tan CRC, Abdul-Majeed S, Cael B, Barta SK (2019) Clinical pharmacokinetics and pharmacodynamics of bortezomib. Clin Pharmacokinet. 58(2):157–168. https://doi.org/10.1007/s40262-018-0679-9CrossRefPubMed

19.

Hellmann A, Rule S, Walewski J, Shpilberg O, Feng H, van de Velde H, Patel H, Skee DM, Girgis S, Louw VJ (2011) Effect of cytochrome P450 3A4 inducers on the pharmacokinetic, pharmacodynamic and safety profiles of bortezomib in patients with multiple myeloma or non-Hodgkin’s lymphoma. Clin Pharmacokinet. 50(12):781–791. https://doi.org/10.2165/11594410-000000000-00000CrossRefPubMed

20.

Yang L, Yan C, Zhang F, Jiang B, Gao S, Liang Y, Huang L, Chen W (2018) Effects of ketoconazole on cyclophosphamide metabolism: evaluation of CYP3A4 inhibition effect using the in vitro and in vivo models. Exp Anim. 67(1):71–82. https://doi.org/10.1538/expanim.17-0048CrossRefPubMed

21.

Kuczma M, Ding ZC, Zhou G (2016) Immunostimulatory Effects of Melphalan and Usefulness in adoptive cell therapy with antitumor CD4+ T cells. Crit Rev Immunol. 36(2):179–191. https://doi.org/10.1615/CritRevImmunol.2016017507CrossRefPubMedPubMedCentral

22.

Nath CE, Shaw PJ, Trotman J, Zeng L, Duffull SB, Hegarty G, McLachlan AJ, Gurney H, Kerridge I, Kwan YL, Presgrave P, Tiley C, Joshua D, Earl J (2010) Population pharmacokinetics of melphalan in patients with multiple myeloma undergoing high dose therapy. Br J Clin Pharmacol. 69(5):484–497. https://doi.org/10.1111/j.1365-2125.2010.03638.xCrossRefPubMedPubMedCentral

23.

Chen N, Zhou S, Palmisano M (2017) Clinical pharmacokinetics and pharmacodynamics of lenalidomide. Clin Pharmacokinet. 56(2):139–152. https://doi.org/10.1007/s40262-016-0432-1CrossRefPubMed

24.

Kasserra C, Assaf M, Hoffmann M, Li Y, Liu L, Wang X et al (2015) Pomalidomide: evaluation of cytochrome P450 and transporter-mediated drug-drug interaction potential in vitro and in healthy subjects. J Clin Pharmacol. 55(2):168–178. https://doi.org/10.1002/jcph.384CrossRefPubMed

25.

Wang Z, Yang J, Kirk C, Fang Y, Alsina M, Badros A et al (2013) Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib. Drug Metab Dispos. 41(1):230–237. https://doi.org/10.1124/dmd.112.047662CrossRefPubMed

Title: A new parameter in multiple myeloma: CYP3A4*1B single nucleotide polymorphism
Authors: Istemi Serin
Sacide Pehlivan
Ilknur Gundes
Yasemin Fidan Oyaci
Mustafa Pehlivan
Publication date: 01-02-2021
Publisher: Springer Berlin Heidelberg
Keywords: Multiple Myeloma
Dexamethasone
Published in: Annals of Hematology / Issue 2/2021
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-020-04339-1

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2021

Prognosis and risk factors for central nervous system relapse after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia

Catching the clinical and biological diversity for an appropriate therapeutic approach in systemic mastocytosis

Carfilzomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma patients: the real-life experience of Rete Ematologica Pugliese (REP)

Prognostic value of ASXL1 mutations in patients with primary myelofibrosis and its relationship with clinical features: a meta-analysis

Clinical association between thyroid disease and immune thrombocytopenia

Prophylaxis, diagnosis and therapy of infections in patients undergoing high-dose chemotherapy and autologous haematopoietic stem cell transplantation. 2020 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials