https://orcid.org/0000-0003-1580-6106
Abstract
Although therapeutic strategies have been adapted to age and comorbidities for a long time, almost all multiple myeloma (MM) patients currently receive similar treatment, whatever their disease risk category. However, high-risk MM patients still constitute an unmet medical need and should benefit from the most efficient drug combinations. Herein, we review and discuss how to optimally define risk and why a revision of the current definition is urgently needed.
REFERENCES
REFERENCES
1.
Chng
WJ
, Dispenzieri
A
, Chim
CS
, et al; International Myeloma Working Group
. IMWG consensus on risk stratification in multiple myeloma
. Leukemia
. 2014
;28
(2
):269
-277
.2.
Pawlyn
C
, Cairns
D
, Kaiser
M
, et al. The relative importance of factors predicting outcome for myeloma patients at different ages: results from 3894 patients in the Myeloma XI trial
. Leukemia
. 2020
;34
(2
):604
-612
.3.
Palumbo
A
, Anderson
K
. Multiple myeloma
. N Engl J Med
. 2011
;364
(11
):1046
-1060
.4.
Kumar
SK
, Gertz
MA
. Risk adapted therapy for multiple myeloma: back to basics
. Leuk Lymphoma
. 2014
;55
(10
):2219
-2220
.5.
Mikhael
JR
, Dingli
D
, Roy
V
, et al; Mayo Clinic
. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013 [published correction appears in Mayo Clin Proc. 2013;88(7):777]
. Mayo Clin Proc
. 2013
;88
(4
):360
-376
.6.
Avet-Loiseau
H
. Ultra high-risk myeloma
. Hematology (Am Soc Hematol Educ Program)
. 2010
;2010
:489
-493
.7.
Usmani
SZ
, Heuck
C
, Mitchell
A
, et al. Extramedullary disease portends poor prognosis in multiple myeloma and is over-represented in high-risk disease even in the era of novel agents
. Haematologica
. 2012
;97
(11
):1761
-1767
.8.
Bladé
J
, de Larrea
CF
, Rosiñol
L
. Extramedullary involvement in multiple myeloma
. Haematologica
. 2012
;97
(11
):1618
-1619
.9.
Corre
J
, Munshi
N
, Avet-Loiseau
H
. Genetics of multiple myeloma: another heterogeneity level?
Blood
. 2015
;125
(12
):1870
-1876
.10.
Robiou du Pont
S
, Cleynen
A
, Fontan
C
, et al. Genomics of multiple myeloma
. J Clin Oncol
. 2017
;35
(9
):963
-967
.11.
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
(2
):100
-113
.12.
Chretien
ML
, Corre
J
, Lauwers-Cances
V
, et al. Understanding the role of hyperdiploidy in myeloma prognosis: which trisomies really matter?
Blood
. 2015
;126
(25
):2713
-2719
.13.
Kumar
S
, Kaufman
JL
, Gasparetto
C
, et al. Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma
. Blood
. 2017
;130
(22
):2401
-2409
.14.
Cleynen
A
, Samur
M
, Perrot
A
, et al. Variable BCL2/BCL2L1 ratio in multiple myeloma with t(11;14)
. Blood
. 2018
;132
(26
):2778
-2780
.15.
Touzeau
C
, Maciag
P
, Amiot
M
, Moreau
P
. Targeting Bcl-2 for the treatment of multiple myeloma
. Leukemia
. 2018
;32
(9
):1899
-1907
.16.
Hebraud
B
, Magrangeas
F
, Cleynen
A
, et al. Role of additional chromosomal changes in the prognostic value of t(4;14) and del(17p) in multiple myeloma: the IFM experience
. Blood
. 2015
;125
(13
):2095
-2100
.17.
San Miguel
JF
, Schlag
R
, Khuageva
NK
, et al; VISTA Trial Investigators
. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma
. N Engl J Med
. 2008
;359
(9
):906
-917
.18.
Avet-Loiseau
H
, Leleu
X
, Roussel
M
, et al. Bortezomib plus dexamethasone induction improves outcome of patients with t(4;14) myeloma but not outcome of patients with del(17p)
. J Clin Oncol
. 2010
;28
(30
):4630
-4634
.19.
Du
C
, Mao
X
, Xu
Y
, et al. 1q21 gain but not t(4;14) indicates inferior outcomes in multiple myeloma treated with bortezomib
. Leuk Lymphoma
. 2020
;61
(5
):1201
-1210
.20.
Avet-Loiseau
H
, Malard
F
, Campion
L
, et al; Intergroupe Francophone du Myélome
. Translocation t(14;16) and multiple myeloma: is it really an independent prognostic factor?
Blood
. 2011
;117
(6
):2009
-2011
.21.
Goldman-Mazur
S
, Jurczyszyn
A
, Castillo
JJ
, et al. A multicenter retrospective study of 223 patients with t(14;16) in multiple myeloma
. Am J Hematol
. 2020
;95
(5
):503
-509
.22.
Palumbo
A
, Avet-Loiseau
H
, Oliva
S
, et al. Revised International Staging System for Multiple Myeloma: a report from International Myeloma Working Group
. J Clin Oncol
. 2015
;33
(26
):2863
-2869
.23.
Walker
BA
, Mavrommatis
K
, Wardell
CP
, et al. A high-risk, double-hit, group of newly diagnosed myeloma identified by genomic analysis
. Leukemia
. 2019
;33
(1
):159
-170
.24.
Schmidt
TM
, Barwick
BG
, Joseph
N
, et al. Gain of chromosome 1q is associated with early progression in multiple myeloma patients treated with lenalidomide, bortezomib, and dexamethasone
. Blood Cancer J
. 2019
;9
(12
):94
.25.
Hebraud
B
, Leleu
X
, Lauwers-Cances
V
, et al. Deletion of the 1p32 region is a major independent prognostic factor in young patients with myeloma: the IFM experience on 1195 patients [published correction appears in Leukemia. 2014;28(3):726]
. Leukemia
. 2014
;28
(3
):675
-679
.26.
Avet-Loiseau
H
, Attal
M
, Moreau
P
, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome
. Blood
. 2007
;109
(8
):3489
-3495
.27.
Thakurta
A
, Ortiz
M
, Blecua
P
, et al. High subclonal fraction of 17p deletion is associated with poor prognosis in multiple myeloma
. Blood
. 2019
;133
(11
):1217
-1221
.28.
Dicker
F
, Herholz
H
, Schnittger
S
, et al. The detection of TP53 mutations in chronic lymphocytic leukemia independently predicts rapid disease progression and is highly correlated with a complex aberrant karyotype
. Leukemia
. 2009
;23
(1
):117
-124
.29.
Corre
J
, Perrot
A
, Caillot
D
, et al. Del17p without TP53 mutation confers poor prognosis in intensively treated newly diagnosed multiple myeloma patients
. Blood
. In press.30.
Chin
M
, Sive
JI
, Allen
C
, et al. Prevalence and timing of TP53 mutations in del(17p) myeloma and effect on survival
. Blood Cancer J
. 2017
;7
(9
):e610
.31.
Samur
MK
, Samur
AA
, Fulciniti
M
, et al. Genome wide somatic alterations in multiple myeloma reveals a superior outcome group
. J Clin Oncol
. 2020
;38
(27
):3107
-3118
.32.
Greipp
PR
, San Miguel
J
, Durie
BG
, et al. International staging system for multiple myeloma [published correction appears in J Clin Oncol. 2005;23(25):6281]
. J Clin Oncol
. 2005
;23
(15
):3412
-3420
.33.
Perrot
A
, Lauwers-Cances
V
, Tournay
E
, et al. Development and validation of a Cytogenetic prognostic index predicting survival in multiple myeloma
. J Clin Oncol
. 2019
;37
(19
):1657
-1665
.34.
Bolli
N
, Li
Y
, Sathiaseelan
V
, et al. A DNA target-enrichment approach to detect mutations, copy number changes and immunoglobulin translocations in multiple myeloma
. Blood Cancer J
. 2016
;6
(9
):e467
.35.
Corre
J
, Montes
L
, Martin
E
, et al. Early relapse after autologous transplant for myeloma is associated with poor survival regardless of cytogenetic risk [published online ahead of print 12 Dec 2019]
. Haematologica
.36.
Durie
BG
, Jacobson
J
, Barlogie
B
, Crowley
J
. Magnitude of response with myeloma frontline therapy does not predict outcome: importance of time to progression in southwest oncology group chemotherapy trials
. J Clin Oncol
. 2004
;22
(10
):1857
-1863
.37.
Kumar
S
, Mahmood
ST
, Lacy
MQ
, et al. Impact of early relapse after auto-SCT for multiple myeloma
. Bone Marrow Transplant
. 2008
;42
(6
):413
-420
.38.
Bal
S
, Weaver
A
, Cornell
RF
, Costa
LJ
. Challenges and opportunities in the assessment of measurable residual disease in multiple myeloma
. Br J Haematol
. 2019
;186
(6
):807
-819
.39.
Perrot
A
, Lauwers-Cances
V
, Corre
J
, et al. Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma
. Blood
. 2018
;132
(23
):2456
-2464
.40.
Paiva
B
, Puig
N
, Cedena
MT
, et al; GEM (Grupo Español de Mieloma)/PETHEMA (Programa Para el Estudio de la Terapéutica en Hemopatías Malignas) Cooperative Study Group
. Measurable residual disease by next-generation flow cytometry in multiple myeloma
. J Clin Oncol
. 2020
;38
(8
):784
-792
.2021
You do not currently have access to this content.
