title: New criteria for response assessment: role of minimal residual disease in multiple myeloma.
abstract: Assessment of minimal residual disease (MRD) is becoming standard diagnostic care for potentially curable neoplasms such as acute lymphoblastic leukemia. In multiple myeloma (MM), the majority of patients will inevitably relapse despite achievement of progressively higher complete remission (CR) rates. Novel treatment protocols with inclusion of antibodies and small molecules might well be able to further increase remission rates and potentially also cure rates. Therefore, MRD diagnostics becomes essential to assess treatment effectiveness. This review summarizes reports from the past 2 decades, which demonstrate that persistent MRD by multiparameter flow cytometry, polymerase chain reaction, next-generation sequencing, and positron emission tomography/computed tomography, predicts significantly inferior survival among CR patients. We describe the specific features of currently available techniques for MRD monitoring and outline the arguments favoring new criteria for response assessment that incorporate MRD levels. Extensive data indicate that MRD information can potentially be used as biomarker to evaluate the efficacy of different treatment strategies, help on treatment decisions, and act as surrogate for overall survival. The time has come to address within clinical trials the exact role of baseline risk factors and MRD monitoring for tailored therapy in MM, which implies systematic usage of highly sensitive, cost-effective, readily available, and standardized MRD techniques.
authors.affiliation: Clinica Universidad de Navarra, Centro de Investigación Médica Aplicada, Pamplona, Spain;
authors.forename: Bruno
authors.initials: B
authors.lastname: Paiva
authors.affiliation: Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands; and.
authors.forename: Jacques J M
authors.initials: JJ
authors.lastname: van Dongen
authors.affiliation: Cancer Research Center Instituto de Biologia Celular y Molecular del Cancer-Consejo Superior de Investigaciones Científicas/University of Salamanca, Department of Medicine Cytometry Service, and Instituto Biosanitario de Salamanca, University of Salamanca, Salamanca, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
mesh_terms: D006801:Humans; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000628:therapy*; D018365:Neoplasm, Residual / Q000175:diagnosis; D016896:Treatment Outcome
references.citation: J Clin Oncol. 2010 Apr 20;28(12):2077-84
references.pmid: 20308672
references.citation: J Clin Oncol. 2014 Sep 1;32(25):2712-7
references.pmid: 25024076
references.citation: Leukemia. 2014 Jun;28(6):1299-307
references.pmid: 24342950
references.citation: Biol Blood Marrow Transplant. 2000;6(3):241-53
references.pmid: 10871149
references.citation: Blood. 2011 Jul 21;118(3):529-34
references.pmid: 21482708
references.citation: Blood. 2012 Jul 5;120(1):9-19
references.pmid: 22498745
references.citation: Blood. 2014 Sep 18;124(12):1887-93
references.pmid: 25102853
references.citation: Leuk Res. 2005 Aug;29(8):961-6
references.pmid: 15978948
references.citation: Cancer. 2008 Jul 15;113(2):355-9
references.pmid: 18470907
references.citation: Lancet Oncol. 2001 Jul;2(7):409-17
references.pmid: 11905735
references.citation: Haematologica. 2004 May;89(5):557-66
references.pmid: 15136219
references.citation: Blood. 2009 Mar 12;113(11):2461-9
references.pmid: 18987362
references.citation: Lancet. 2010 Dec 18;376(9758):2075-85
references.pmid: 21146205
references.citation: J Clin Oncol. 2013 Sep 10;31(26):3279-87
references.pmid: 23897961
references.citation: Blood. 2002 Mar 1;99(5):1853-6
references.pmid: 11861305
references.citation: Blood. 2009 Dec 3;114(24):4954-6
references.pmid: 19797521
references.citation: Blood. 2014 Jul 17;124(3):328-33
references.pmid: 24894774
references.citation: Haematologica. 2012 Nov;97(11):1757-60
references.pmid: 22689673
references.citation: Leukemia. 2012 Sep;26(9):1908-75
references.pmid: 22552007
references.citation: Blood. 2009 Nov 12;114(20):4369-72
references.pmid: 19755674
references.citation: J Clin Oncol. 2014 Mar 1;32(7):634-40
references.pmid: 24449241
references.citation: Blood. 2014 Nov 13;124(20):3043-51
references.pmid: 25293776
references.citation: J Clin Oncol. 2011 Apr 20;29(12):1627-33
references.pmid: 21402611
references.citation: Leukemia. 2014 Feb;28(2):258-68
references.pmid: 23868105
references.citation: Br J Haematol. 2012 Dec;159(5):499-513
references.pmid: 22881361
references.citation: Am J Hematol. 2014 Dec;89(12):1159-60
references.pmid: 25132630
references.citation: J Clin Oncol. 2008 Dec 10;26(35):5775-82
references.pmid: 19001321
references.citation: Sci Transl Med. 2009 Dec 23;1(12):12ra23
references.pmid: 20161664
references.citation: Cancer Cell. 2013 Sep 9;24(3):289-304
references.pmid: 24029229
references.citation: Haematologica. 2014 Apr;99(4):629-37
references.pmid: 24688111
references.citation: Haematologica. 2014 Jan;99(1):155-62
references.pmid: 23872308
references.citation: Leukemia. 2007 Apr;21(4):706-13
references.pmid: 17287857
references.citation: Am Soc Clin Oncol Educ Book. 2013;. doi: 10.1200/EdBook_AM.2013.33.e313
references.pmid: 23714534
references.citation: Haematologica. 2013 Jul;98(7):1142-6
references.pmid: 23645688
references.citation: Blood. 2015 Mar 19;125(12):1932-5
references.pmid: 25645353
references.citation: J Clin Oncol. 2000 Jun;18(11):2273-81
references.pmid: 10829048
references.citation: Haematologica. 2015 Feb;100(2):e53-5
references.pmid: 25381128
references.citation: Blood. 2011 Dec 1;118(23):5989-95
references.pmid: 21900189
references.citation: Leukemia. 2013 Jan;27(1):226-32
references.pmid: 22705990
references.citation: Blood. 2014 May 15;123(20):3061-2
references.pmid: 24832937
references.citation: Blood. 2011 Dec 1;118(23):5984-5
references.pmid: 22134907
references.citation: Blood. 2012 Dec 20;120(26):5173-80
references.pmid: 23074282
references.citation: Blood. 2012 Jan 19;119(3):687-91
references.pmid: 22128143
references.citation: Blood. 2009 Sep 3;114(10):2068-76
references.pmid: 19443657
references.citation: Leukemia. 2015 May;29(5):1186-94
references.pmid: 25388955
references.citation: Blood. 2002 Nov 1;100(9):3095-100
references.pmid: 12384404
references.citation: Blood. 2011 Jun 9;117(23):6063-73
references.pmid: 21447828
references.citation: Blood. 2000 Jul 1;96(1):355-7
references.pmid: 10891473
references.citation: Br J Haematol. 2011 Jun;153(6):721-8
references.pmid: 21517815
references.citation: Haematologica. 2010 Jun;95(6):1016-20
references.pmid: 20081059
references.citation: Leukemia. 2013 Oct;27(10):2056-61
references.pmid: 23743858
references.citation: Blood. 2013 Jun 6;121(23):4647-54
references.pmid: 23616624
references.citation: Blood. 2011 Jul 21;118(3):535-43
references.pmid: 21596852
references.citation: Blood. 2010 Aug 5;116(5):679-86
references.pmid: 20385792
references.citation: Haematologica. 2010 Oct;95(10):1738-44
references.pmid: 20460639
references.citation: Leukemia. 2007 Feb;21(2):207-14
references.pmid: 17170731
references.citation: Blood. 2003 Sep 1;102(5):1927-9
references.pmid: 12738666
references.citation: Leukemia. 2014 Oct;28(10):2075-9
references.pmid: 24637336
references.citation: Leukemia. 2003 Dec;17(12):2257-317
references.pmid: 14671650
references.citation: Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21194-9
references.pmid: 22160699
references.citation: Br J Haematol. 1999 Oct;107(1):121-31
references.pmid: 10520032
references.citation: Blood. 2012 Aug 23;120(8):1589-96
references.pmid: 22791289
references.citation: Lancet. 2007 Oct 6;370(9594):1209-18
references.pmid: 17920916
references.citation: J Clin Oncol. 2013 Jul 10;31(20):2540-7
references.pmid: 23733781
references.citation: Leukemia. 2014 Feb;28(2):239-40
references.pmid: 24496282
references.citation: J Clin Oncol. 2012 Mar 20;30(9):980-8
references.pmid: 22331940
references.citation: N Engl J Med. 2014 Sep 4;371(10):895-905
references.pmid: 25184862
references.citation: Eur J Haematol. 2012 Oct;89(4):328-35
references.pmid: 22805350
references.citation: J Clin Oncol. 2013 Dec 20;31(36):4529-35
references.pmid: 24248686
references.citation: Bone Marrow Transplant. 2008 May;41(10):913-6
references.pmid: 18264143
references.citation: Blood. 2014 May 15;123(20):3073-9
references.pmid: 24646471
references.citation: Haematologica. 2005 Oct;90(10):1365-72
references.pmid: 16219573
references.citation: N Engl J Med. 2015 Jan 8;372(2):142-52
references.pmid: 25482145
references.citation: Br J Haematol. 2004 Sep;126(5):665-74
references.pmid: 15327517
references.citation: N Engl J Med. 2008 Aug 28;359(9):906-17
references.pmid: 18753647
references.citation: Leukemia. 2016 May;30(5):1211-4
references.pmid: 26437784
references.citation: Leukemia. 2006 Sep;20(9):1467-73
references.pmid: 16855634
references.citation: Blood Cancer J. 2014;4:e250
references.pmid: 25303369
references.citation: Haematologica. 2007 Oct;92(10):1399-406
references.pmid: 18024376
references.citation: Leukemia. 2014 Feb;28(2):391-7
references.pmid: 23860448
references.citation: Blood. 2007 Feb 15;109(4):1692-700
references.pmid: 17023574
references.citation: N Engl J Med. 2007 Nov 22;357(21):2123-32
references.pmid: 18032762
references.citation: N Engl J Med. 2005 Jun 16;352(24):2487-98
references.pmid: 15958804
references.citation: Blood. 2008 Nov 15;112(10):4017-23
references.pmid: 18669875
references.citation: Br J Haematol. 1998 Sep;102(5):1115-23
references.pmid: 9753033
references.citation: Leukemia. 2014 Mar;28(3):525-42
references.pmid: 24253022
references.citation: Haematologica. 2008 Mar;93(3):431-8
references.pmid: 18268286
references.citation: Leukemia. 2010 Nov;24(11):1927-33
references.pmid: 20844562
references.citation: Leukemia. 2015 Mar;29(3):689-95
references.pmid: 25027515
references.citation: Clin Chem. 2009 Aug;55(8):1510-6
references.pmid: 19520760
references.citation: Eur J Haematol. 2010 Nov;85(5):416-23
references.pmid: 20722702
references.citation: J Clin Oncol. 2011 Oct 1;29(28):3805-12
references.pmid: 21900099
references.citation: Leukemia. 2014 Mar;28(3):690-3
references.pmid: 24220275
references.citation: Leukemia. 2013 Jan;27(1):213-9
references.pmid: 22955329
references.citation: Blood. 2011 Mar 17;117(11):3025-31
references.pmid: 21228328
references.citation: Blood. 2013 Aug 8;122(6):1088-9
references.pmid: 23929839
references.citation: Cytometry B Clin Cytom. 2010 Jul;78(4):239-52
references.pmid: 20155853