Prognostic or predictive value of circulating cytokines and angiogenic factors for initial treatment of multiple myeloma in the GIMEMA MM0305 randomized controlled trial.
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Becaplermin
/ blood
Biomarkers, Tumor
/ blood
Bone Marrow
Female
Fibroblast Growth Factor 2
/ blood
Follow-Up Studies
Hepatocyte Growth Factor
/ blood
Humans
Logistic Models
Male
Middle Aged
Multiple Myeloma
/ blood
Prognosis
Progression-Free Survival
ROC Curve
Vascular Endothelial Growth Factor A
/ blood
Angiogenic factors
Multiple myeloma
Overall survival
Progression-free survival
Response rate
Journal
Journal of hematology & oncology
ISSN: 1756-8722
Titre abrégé: J Hematol Oncol
Pays: England
ID NLM: 101468937
Informations de publication
Date de publication:
09 01 2019
09 01 2019
Historique:
received:
22
09
2018
accepted:
25
12
2018
entrez:
11
1
2019
pubmed:
11
1
2019
medline:
11
3
2020
Statut:
epublish
Résumé
Several new drugs are approved for treatment of patients with multiple myeloma (MM), but no validated biomarkers are available for the prediction of a clinical outcome. We aimed to establish whether pretreatment blood and bone marrow plasma concentrations of major cytokines and angiogenic factors (CAFs) of patients from a phase 3 trial of a MM treatment could have a prognostic and predictive value in terms of response to therapy and progression-free and overall survival and whether these patients could be stratified for their prognosis. Blood and bone marrow plasma levels of Ang-2, FGF-2, HGF, VEGF, PDGF-β, IL-8, TNF-α, TIMP-1, and TIMP-2 were determined at diagnosis in MM patients enrolled in the GIMEMA MM0305 randomized controlled trial by an enzyme-linked immunosorbent assay (ELISA). These levels were correlated both reciprocally and with the type of therapy and patients' characteristics and with a group of non-MM patients as controls. No significant differences were detected between the blood and bone marrow plasma levels of angiogenic cytokines. A cutoff for each CAF was established. The therapeutic response of patients with blood plasma levels of CAFs lower than the cutoff was better than the response of those with higher levels in terms of percentage of responding patients and quality of response. FGF-2, HGF, VEGF, and PDGF-β plasma levels at diagnosis have predictive significance for response to treatment. The stratification of patients based on the levels of CAFs at diagnosis and their variations after therapy is useful to characterize different risk groups concerning outcome and response to therapy. Clinical trial information can be found at the following link: NCT01063179.
Sections du résumé
BACKGROUND
Several new drugs are approved for treatment of patients with multiple myeloma (MM), but no validated biomarkers are available for the prediction of a clinical outcome. We aimed to establish whether pretreatment blood and bone marrow plasma concentrations of major cytokines and angiogenic factors (CAFs) of patients from a phase 3 trial of a MM treatment could have a prognostic and predictive value in terms of response to therapy and progression-free and overall survival and whether these patients could be stratified for their prognosis.
METHODS
Blood and bone marrow plasma levels of Ang-2, FGF-2, HGF, VEGF, PDGF-β, IL-8, TNF-α, TIMP-1, and TIMP-2 were determined at diagnosis in MM patients enrolled in the GIMEMA MM0305 randomized controlled trial by an enzyme-linked immunosorbent assay (ELISA). These levels were correlated both reciprocally and with the type of therapy and patients' characteristics and with a group of non-MM patients as controls.
RESULTS
No significant differences were detected between the blood and bone marrow plasma levels of angiogenic cytokines. A cutoff for each CAF was established. The therapeutic response of patients with blood plasma levels of CAFs lower than the cutoff was better than the response of those with higher levels in terms of percentage of responding patients and quality of response.
CONCLUSION
FGF-2, HGF, VEGF, and PDGF-β plasma levels at diagnosis have predictive significance for response to treatment. The stratification of patients based on the levels of CAFs at diagnosis and their variations after therapy is useful to characterize different risk groups concerning outcome and response to therapy.
TRIAL REGISTRATION
Clinical trial information can be found at the following link: NCT01063179.
Identifiants
pubmed: 30626425
doi: 10.1186/s13045-018-0691-4
pii: 10.1186/s13045-018-0691-4
pmc: PMC6327520
doi:
Substances chimiques
Biomarkers, Tumor
0
HGF protein, human
0
VEGFA protein, human
0
Vascular Endothelial Growth Factor A
0
Fibroblast Growth Factor 2
103107-01-3
Becaplermin
1B56C968OA
Hepatocyte Growth Factor
67256-21-7
Banques de données
ClinicalTrials.gov
['NCT01063179']
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4Références
Lancet. 2007 Dec 22;370(9605):2103-11
pubmed: 18156031
Clin Cancer Res. 2010 Oct 1;16(19):4853-63
pubmed: 20651059
J Clin Oncol. 2010 Jan 20;28(3):475-80
pubmed: 20008644
Lancet Oncol. 2012 Aug;13(8):827-37
pubmed: 22759480
Lancet. 2006 Mar 11;367(9513):825-31
pubmed: 16530576
Am J Blood Res. 2011;1(1):76-89
pubmed: 22432068
Blood. 2011 Nov 24;118(22):5759-66
pubmed: 21951682
N Engl J Med. 2007 Jan 11;356(2):125-34
pubmed: 17215530
Cancer Lett. 2004 Dec 8;216(1):103-7
pubmed: 15500953
J Clin Oncol. 1998 Dec;16(12):3832-42
pubmed: 9850028
Cancer Prev Res (Phila). 2011 Oct;4(10):1590-8
pubmed: 21764858
Clin Adv Hematol Oncol. 2013 Aug;11(8):489-503
pubmed: 24518420
J Clin Oncol. 2009 Aug 1;27(22):3664-70
pubmed: 19451428
World J Methodol. 2014 Jun 26;4(2):73-90
pubmed: 25332907
J Clin Oncol. 2005 May 20;23(15):3412-20
pubmed: 15809451
J Clin Oncol. 2014 Mar 1;32(7):634-40
pubmed: 24449241
J Clin Oncol. 2010 Feb 20;28(6):1061-8
pubmed: 20100962
N Engl J Med. 2007 Nov 22;357(21):2123-32
pubmed: 18032762
N Engl J Med. 2007 Nov 22;357(21):2133-42
pubmed: 18032763
Expert Rev Hematol. 2014 Feb;7(1):21-31
pubmed: 24483346
JAMA. 1969 Jun 2;208(9):1680-5
pubmed: 5818682
Clin Lymphoma Myeloma Leuk. 2018 Apr;18(4):235-248
pubmed: 29506935
N Engl J Med. 2005 Jun 16;352(24):2487-98
pubmed: 15958804
Blood. 2012 Jan 26;119(4):940-8
pubmed: 22160383
N Engl J Med. 2008 Aug 28;359(9):906-17
pubmed: 18753647
Ann Oncol. 2012 Jan;23(1):46-52
pubmed: 21464158
Chem Immunol Allergy. 2014;99:180-96
pubmed: 24217610
Clin Cancer Res. 2014 Feb 15;20(4):804-13
pubmed: 24270684
Head Neck. 2000 Oct;22(7):666-73
pubmed: 11002321
Leukemia. 2014 Feb;28(2):269-77
pubmed: 23974982
Adv Hematol. 2017;2017:4812637
pubmed: 28321258
Expert Rev Anticancer Ther. 2012 Oct;12(10):1253-61
pubmed: 23136836
N Engl J Med. 2004 Oct 28;351(18):1860-73
pubmed: 15509819
J Clin Oncol. 2009 Dec 1;27(34):5794-9
pubmed: 19826129
J Clin Oncol. 2010 Dec 1;28(34):5101-9
pubmed: 20940200
Cancer Invest. 2015;33(10):496-504
pubmed: 26506456
N Engl J Med. 2007 Jan 11;356(2):115-24
pubmed: 17215529
Semin Nucl Med. 2015 Jan;45(1):16-31
pubmed: 25475376
Clin Exp Med. 2008 Sep;8(3):141-5
pubmed: 18791686
Cancer. 1975 Sep;36(3):842-54
pubmed: 1182674
Br J Haematol. 2009 Nov;147(3):347-51
pubmed: 19702643
Clin Cancer Res. 2011 Apr 1;17(7):1935-46
pubmed: 21307145
Lancet. 2007 Oct 6;370(9594):1209-18
pubmed: 17920916
Cancer Res. 2010 Mar 15;70(6):2171-9
pubmed: 20215520
Eur J Cancer. 2010 Jan;46(2):420-9
pubmed: 19914061
J Clin Oncol. 2010 Jan 10;28(2):193-201
pubmed: 19949019
Cancer Res. 2006 Jan 1;66(1):184-91
pubmed: 16397231
Biol Blood Marrow Transplant. 2012 Dec;18(12):1790-9
pubmed: 22626785
Hormones (Athens). 2006 Apr-Jun;5(2):137-46
pubmed: 16807226
Nature. 2000 Sep 14;407(6801):249-57
pubmed: 11001068
J Clin Oncol. 2007 Oct 1;25(28):4459-65
pubmed: 17785703