Skip to main content
Top
Published in: Medical Oncology 9/2019

01-09-2019 | Multiple Myeloma | Original Paper

MPC-1 expression in myeloma cells is associated with the efficacy of bortezomib therapy

Authors: Kazuya Kurihara, Noriyoshi Iriyama, Katsuhiro Miura, Yoshihito Uchino, Hiromichi Takahashi, Masaru Nakagawa, Kazuhide Iizuka, Takashi Hamada, Takashi Koike, Yoshihiro Hatta, Tomohiro Nakayama, Masami Takei

Published in: Medical Oncology | Issue 9/2019

Login to get access

Abstract

The use of bortezomib in the clinic has significantly improved outcomes for patients with multiple myeloma (MM), even those harboring high-risk cytogenetic abnormalities or those classified in the high-risk category according to the International Staging System (ISS). In this study, we analyzed the association between immunophenotyping on myeloma cells and the clinical outcomes of patients who received bortezomib-based regimens as first-line therapy. Immunophenotypic analysis before bortezomib therapy was performed by flow cytometry, and whether the immunophenotyping results influenced the clinical outcomes of the patients was investigated. Seventy-four newly diagnosed patients with MM were included in this study. We found that the expression of MPC-1 significantly predicted the time to next therapy (TNT), with a longer TNT in the MPC-1 positive group (p = 0.005), whereas it did not affect overall survival (OS; p = 0.773). In addition, we found that CD45-positivity was associated with shorter TNT (p = 0.0432). Following ISS assessment at treatment initiation, patients who were classified as stage I showed a slightly longer OS compared to those at stage II or III; however, these results were not significant (p = 0.0987). Furthermore, multivariate analysis revealed the prognostic significance of MPC-1 expression, as MPC-1-negativity was associated with a worse TNT. The combination of MPC-1 and CD45 status more sensibly predicted the TNT for bortezomib therapy. Our results demonstrate the clinical importance of immunophenotyping on myeloma cells to determine patient prognoses in this era of novel therapeutic agents.
Literature
1.
go back to reference Pawlyn C, Davies FE. Toward personalized treatment in multiple myeloma based on molecular characteristics. Blood. 2019;133:660–75.CrossRef Pawlyn C, Davies FE. Toward personalized treatment in multiple myeloma based on molecular characteristics. Blood. 2019;133:660–75.CrossRef
2.
go back to reference Corre J, Munshi N, Avet-Loiseau H. Genetics of multiple myeloma: another heterogeneity level? Blood. 2015;125:1870–6.CrossRef Corre J, Munshi N, Avet-Loiseau H. Genetics of multiple myeloma: another heterogeneity level? Blood. 2015;125:1870–6.CrossRef
3.
go back to reference Bianchi G, Munshi NC. Pathogenesis beyond the cancer clone(s) in multiple myeloma. Blood. 2015;125:3049–58.CrossRef Bianchi G, Munshi NC. Pathogenesis beyond the cancer clone(s) in multiple myeloma. Blood. 2015;125:3049–58.CrossRef
4.
go back to reference Manier S, Salem KZ, Park J, Landau DA, Getz G, Ghobrial IM. Genomic complexity of multiple myeloma and its clinical implications. Nat Rev Clin Oncol. 2017;14:100–13.CrossRef Manier S, Salem KZ, Park J, Landau DA, Getz G, Ghobrial IM. Genomic complexity of multiple myeloma and its clinical implications. Nat Rev Clin Oncol. 2017;14:100–13.CrossRef
5.
go back to reference Corre J, Cleynen A, Robiou du Pont S, Buisson L, Bolli N, et al. Multiple myeloma clonal evolution in homogeneously treated patients. Leukemia. 2018;32:2636–47.CrossRef Corre J, Cleynen A, Robiou du Pont S, Buisson L, Bolli N, et al. Multiple myeloma clonal evolution in homogeneously treated patients. Leukemia. 2018;32:2636–47.CrossRef
6.
7.
go back to reference Chim CS, Kumar SK, Orlowski RZ, Cook G, Richardson PG, Gertz MA, et al. Management of relapsed and refractory multiple myeloma: novel agents, antibodies, immunotherapies and beyond. Leukemia. 2018;32:252–62.CrossRef Chim CS, Kumar SK, Orlowski RZ, Cook G, Richardson PG, Gertz MA, et al. Management of relapsed and refractory multiple myeloma: novel agents, antibodies, immunotherapies and beyond. Leukemia. 2018;32:252–62.CrossRef
8.
go back to reference Moreau P, Richardson PG, Cavo M, Orlowski RZ, San Miguel JF, Palumbo A, Harousseau JL. Proteasome inhibitors in multiple myeloma: 10 years later. Blood. 2012;120:947–59.CrossRef Moreau P, Richardson PG, Cavo M, Orlowski RZ, San Miguel JF, Palumbo A, Harousseau JL. Proteasome inhibitors in multiple myeloma: 10 years later. Blood. 2012;120:947–59.CrossRef
9.
go back to reference Liu J, Yang H, Liang X, Wang Y, Hou J, Liu Y, et al. Meta-analysis of the efficacy of treatments for newly diagnosed and relapsed/refractory multiple myeloma with del(17p). Oncotarget. 2017;8:62435–44.PubMedPubMedCentral Liu J, Yang H, Liang X, Wang Y, Hou J, Liu Y, et al. Meta-analysis of the efficacy of treatments for newly diagnosed and relapsed/refractory multiple myeloma with del(17p). Oncotarget. 2017;8:62435–44.PubMedPubMedCentral
10.
go back to reference Sonneveld P, Avet-Loiseau H, Lonial S, Usmani S, Siegel D, Anderson KC, et al. Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. Blood. 2016;127:2955–62.CrossRef Sonneveld P, Avet-Loiseau H, Lonial S, Usmani S, Siegel D, Anderson KC, et al. Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. Blood. 2016;127:2955–62.CrossRef
11.
go back to reference Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, et al. International Staging System for multiple myeloma. J Clin Oncol. 2005;23:3412–20.CrossRef Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, et al. International Staging System for multiple myeloma. J Clin Oncol. 2005;23:3412–20.CrossRef
12.
go back to reference Harada H, Kawano MM, Huang N, Harada Y, Iwato K, Tanabe O, et al. Phenotypic difference of normal plasma cells from mature myeloma cells. Blood. 1993;81:2658–63.PubMed Harada H, Kawano MM, Huang N, Harada Y, Iwato K, Tanabe O, et al. Phenotypic difference of normal plasma cells from mature myeloma cells. Blood. 1993;81:2658–63.PubMed
13.
go back to reference Huang N, Kawano MM, Harada H, Harada Y, Sakai A, Kuramoto A, Niwa O. Heterogeneous expression of a novel MPC-1 antigen on myeloma cells: possible involvement of MPC-1 antigen in the adhesion of mature myeloma cells to bone marrow stromal cells. Blood. 1993;82:3721–9.PubMed Huang N, Kawano MM, Harada H, Harada Y, Sakai A, Kuramoto A, Niwa O. Heterogeneous expression of a novel MPC-1 antigen on myeloma cells: possible involvement of MPC-1 antigen in the adhesion of mature myeloma cells to bone marrow stromal cells. Blood. 1993;82:3721–9.PubMed
14.
go back to reference Iriyama N, Miura K, Hatta Y, Uchino Y, Kurita D, Takahashi H, et al. Plasma cell maturity as a predictor of prognosis in multiple myeloma. Med Oncol. 2016;33:87.CrossRef Iriyama N, Miura K, Hatta Y, Uchino Y, Kurita D, Takahashi H, et al. Plasma cell maturity as a predictor of prognosis in multiple myeloma. Med Oncol. 2016;33:87.CrossRef
15.
go back to reference Lin K-I, Tunyaplin C, Calame K. Transcriptional regulatory cascades controlling plasma cell differentiation. Immunol Rev. 2003;194:19–28.CrossRef Lin K-I, Tunyaplin C, Calame K. Transcriptional regulatory cascades controlling plasma cell differentiation. Immunol Rev. 2003;194:19–28.CrossRef
16.
go back to reference Iwakoshi NN, Lee A-H, Vallabhajosyula P, Otipoby KL, Rajewsky K, Glimcher LH. Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1. Nat Immunol. 2003;4:321–9.CrossRef Iwakoshi NN, Lee A-H, Vallabhajosyula P, Otipoby KL, Rajewsky K, Glimcher LH. Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1. Nat Immunol. 2003;4:321–9.CrossRef
17.
go back to reference Bagratuni T, Wu P, GonzalezdeCastro D, Davenport EL, Dickens NJ, Walker BA, et al. XBP1 s levels are implicated in the biology and outcome of myeloma mediating different clinical outcomes to thalidomide-based treatments. Blood. 2010;116:250–3.CrossRef Bagratuni T, Wu P, GonzalezdeCastro D, Davenport EL, Dickens NJ, Walker BA, et al. XBP1 s levels are implicated in the biology and outcome of myeloma mediating different clinical outcomes to thalidomide-based treatments. Blood. 2010;116:250–3.CrossRef
18.
go back to reference Iriyama N, Miura K, Hatta Y, Kobayashi S, Uchino Y, Kurita D, et al. Clinical effect of immunophenotyping on the prognosis of multiple myeloma patients treated with bortezomib. Oncol Lett. 2017;13:3803–8.CrossRef Iriyama N, Miura K, Hatta Y, Kobayashi S, Uchino Y, Kurita D, et al. Clinical effect of immunophenotyping on the prognosis of multiple myeloma patients treated with bortezomib. Oncol Lett. 2017;13:3803–8.CrossRef
19.
go back to reference Reeder CB, Reece DE, Kukreti V, Chen C, Trudel S, Hentz J, et al. Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia. 2009;23:1337–41.CrossRef Reeder CB, Reece DE, Kukreti V, Chen C, Trudel S, Hentz J, et al. Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia. 2009;23:1337–41.CrossRef
20.
go back to reference San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008;359:906–17.CrossRef San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008;359:906–17.CrossRef
21.
go back to reference Ri M. Endoplasmic-reticulum stress pathway-associated mechanisms of action of proteasome inhibitors in multiple myeloma. Int J Hematol. 2016;104:273–80.CrossRef Ri M. Endoplasmic-reticulum stress pathway-associated mechanisms of action of proteasome inhibitors in multiple myeloma. Int J Hematol. 2016;104:273–80.CrossRef
22.
go back to reference Leung-Hagesteijn C, Erdmann N, Cheung G, Keats JJ, Stewart AK, Reece DE, et al. Xbp1 s-negative tumor B cells and pre-plasmablasts mediate therapeutic proteasome inhibitor resistance in multiple myeloma. Cancer Cell. 2013;24:289–304.CrossRef Leung-Hagesteijn C, Erdmann N, Cheung G, Keats JJ, Stewart AK, Reece DE, et al. Xbp1 s-negative tumor B cells and pre-plasmablasts mediate therapeutic proteasome inhibitor resistance in multiple myeloma. Cancer Cell. 2013;24:289–304.CrossRef
23.
go back to reference Kuroda Y, Sakai A, Okikawa Y, Munemasa S, Katayama Y, Hyodo H, et al. The maturation of myeloma cells correlates with sensitivity to chemotherapeutic agents. Int J Hematol. 2005;81:335–41.CrossRef Kuroda Y, Sakai A, Okikawa Y, Munemasa S, Katayama Y, Hyodo H, et al. The maturation of myeloma cells correlates with sensitivity to chemotherapeutic agents. Int J Hematol. 2005;81:335–41.CrossRef
24.
go back to reference Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, Spicka I, et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373:621–31.CrossRef Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, Spicka I, et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373:621–31.CrossRef
25.
go back to reference Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:1319–31.CrossRef Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:1319–31.CrossRef
26.
go back to reference Costa LJ, Brill IK, Omel J, Godby K, Kumar SK, Brown EE. Recent trends in multiple myeloma incidence and survival by age, race, and ethnicity in the United States. Blood Adv. 2017;1:282–7.CrossRef Costa LJ, Brill IK, Omel J, Godby K, Kumar SK, Brown EE. Recent trends in multiple myeloma incidence and survival by age, race, and ethnicity in the United States. Blood Adv. 2017;1:282–7.CrossRef
27.
go back to reference Gonsalves WI, Timm MM, Rajkumar SV, Morice WG, Dispenzieri A, Buadi FK, et al. The prognostic significance of CD45 expression by clonal bone marrow plasma cells in patients with newly diagnosed multiple myeloma. Leuk Res. 2016;44:32–9.CrossRef Gonsalves WI, Timm MM, Rajkumar SV, Morice WG, Dispenzieri A, Buadi FK, et al. The prognostic significance of CD45 expression by clonal bone marrow plasma cells in patients with newly diagnosed multiple myeloma. Leuk Res. 2016;44:32–9.CrossRef
28.
go back to reference Moreau P, Robillard N, Avet-Loiseau H, Pineau D, Morineau N, Milpied N, et al. Patients with CD45 negative multiple myeloma receiving high-dose therapy have a shorter survival than those with CD45 positive multiple myeloma. Haematologica. 2004;89:547–51.PubMed Moreau P, Robillard N, Avet-Loiseau H, Pineau D, Morineau N, Milpied N, et al. Patients with CD45 negative multiple myeloma receiving high-dose therapy have a shorter survival than those with CD45 positive multiple myeloma. Haematologica. 2004;89:547–51.PubMed
29.
go back to reference Kuroda J, Shimura Y, Ohta K, Tanaka H, Shibayama H, Kosugi S, et al. Limited value of the International Staging System for predicting long-term outcome of transplant-ineligible, newly diagnosed, symptomatic multiple myeloma in the era of novel agents. Int J Hematol. 2014;99:441–9.CrossRef Kuroda J, Shimura Y, Ohta K, Tanaka H, Shibayama H, Kosugi S, et al. Limited value of the International Staging System for predicting long-term outcome of transplant-ineligible, newly diagnosed, symptomatic multiple myeloma in the era of novel agents. Int J Hematol. 2014;99:441–9.CrossRef
30.
go back to reference Tan D, Kim K, Kim JS, Eom HS, Teoh G, Ong KH, et al. The impact of upfront versus sequential use of bortezomib among patients with newly diagnosed multiple myeloma (MM): a joint analysis of the Singapore MM Study Group and the Korean MM Working Party for the Asian myeloma network. Leuk Res. 2013;37:1070–6.CrossRef Tan D, Kim K, Kim JS, Eom HS, Teoh G, Ong KH, et al. The impact of upfront versus sequential use of bortezomib among patients with newly diagnosed multiple myeloma (MM): a joint analysis of the Singapore MM Study Group and the Korean MM Working Party for the Asian myeloma network. Leuk Res. 2013;37:1070–6.CrossRef
31.
go back to reference Maltezas D, Dimopoulos MA, Katodritou I, Repousis P, Pouli A, Terpos E, et al. Re-evaluation of prognostic markers including staging, serum free light chains or their ratio and serum lactate dehydrogenase in multiple myeloma patients receiving novel agents. Hematol Oncol. 2013;31:356–62.CrossRef Maltezas D, Dimopoulos MA, Katodritou I, Repousis P, Pouli A, Terpos E, et al. Re-evaluation of prognostic markers including staging, serum free light chains or their ratio and serum lactate dehydrogenase in multiple myeloma patients receiving novel agents. Hematol Oncol. 2013;31:356–62.CrossRef
32.
go back to reference Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, et al. Revised International Staging System for multiple myeloma: a Report From International Myeloma Working Group. J Clin Oncol. 2015;33:2863–9.CrossRef Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, et al. Revised International Staging System for multiple myeloma: a Report From International Myeloma Working Group. J Clin Oncol. 2015;33:2863–9.CrossRef
Metadata
Title
MPC-1 expression in myeloma cells is associated with the efficacy of bortezomib therapy
Authors
Kazuya Kurihara
Noriyoshi Iriyama
Katsuhiro Miura
Yoshihito Uchino
Hiromichi Takahashi
Masaru Nakagawa
Kazuhide Iizuka
Takashi Hamada
Takashi Koike
Yoshihiro Hatta
Tomohiro Nakayama
Masami Takei
Publication date
01-09-2019
Publisher
Springer US
Published in
Medical Oncology / Issue 9/2019
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-019-1298-5

Other articles of this Issue 9/2019

Medical Oncology 9/2019 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

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

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.