• Cost-effectiveness of first- and second-line use of daratumumab for transplant-eligible NDMM patients was compared using a Markov model.

  • First-line use dominated second-line use of daratumumab with higher QALY and lower cost over 10-year time horizon.

Triplet regimens, such as lenalidomide, bortezomib, and dexamethasone (RVd) or thalidomide, bortezomib, and dexamethasone (VTd), are standard induction therapies for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). The addition of daratumumab to RVd and VTd has been investigated in the GRIFFIN and CASSIOPEIA trials, respectively, resulting in improvement in the rate of minimal residual disease (MRD) negativity. In this study, we conducted a cost-effectiveness analysis with a 10-year time horizon to compare first-line and second-line use of daratumumab for transplant-eligible patients with NDMM. Because long-term follow-up data for these clinical trials are not yet available, we developed a Markov model that uses MRD status to predict progression-free survival. Daratumumab was used either in the first-line setting in combination with RVd or VTd or in the second-line setting with carfilzomib plus dexamethasone (Kd). Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios were calculated from a Japanese and US payer perspective. In the Japanese analysis, D-RVd showed higher QALYs (5.43 vs 5.18) and lower costs (¥64 479,793 vs ¥71  287 569) compared with RVd, and D-VTd showed higher QALYs (5.67 vs 5.42) and lower costs (¥43  600 310 vs ¥49 471,941) compared with VTd. Similarly, the US analysis demonstrated dominance of a strategy incorporating daratumumab in first-line treatment regimens. Given that overall costs are reduced and outcomes are improved when daratumumab is used as part of a first-line regimen, the economic analysis indicates that addition of daratumumab to first-line RVd and VTd regimens is a dominant strategy compared with reserving its use for the second-line setting.

1.
Voorhees
PM
,
Kaufman
JL
,
Laubach
J
, et al
.
Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial
.
Blood.
2020
;
136
(
8
):
936
-
945
.
2.
Voorhees
PM
,
Rodriguez
C
,
Reeves
B
, et al
.
Daratumumab plus RVd for newly diagnosed multiple myeloma: final analysis of the safety run-in cohort of GRIFFIN
.
Blood Adv.
2021
;
5
(
4
):
1092
-
1096
.
3.
Roussel
M
,
Moreau
P
,
Hebraud
B
, et al
.
Bortezomib, thalidomide, and dexamethasone with or without daratumumab for transplantation-eligible patients with newly diagnosed multiple myeloma (CASSIOPEIA): health-related quality of life outcomes of a randomised, open-label, phase 3 trial
.
Lancet Haematol.
2020
;
7
(
12
):
e874
-
e883
.
4.
Moreau
P
,
Hulin
C
,
Perrot
A
, et al
.
Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial
.
Lancet Oncol.
2021
;
22
(
10
):
1378
-
1390
.
5.
Laubach
JP
,
Kaufman
JL
,
Sborov
DW
, et al
.
Daratumumab (DARA) plus lenalidomide, bortezomib, and dexamethasone (RVd) in patients (Pts) with transplant-eligible newly diagnosed multiple myeloma (NDMM): updated analysis of Griffin after 24 months of maintenance
[abstract].
Blood.
2021
;
138
(
suppl 1
). Abstract 79.
6.
Costa
LJ
,
Derman
BA
,
Bal
S
, et al
.
International harmonization in performing and reporting minimal residual disease assessment in multiple myeloma trials
.
Leukemia.
2021
;
35
(
1
):
18
-
30
.
7.
Kumar
S
,
Paiva
B
,
Anderson
KC
, et al
.
International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma
.
Lancet Oncol.
2016
;
17
(
8
):
e328
-
e346
.
8.
Munshi
NC
,
Avet-Loiseau
H
,
Anderson
KC
, et al
.
A large meta-analysis establishes the role of MRD negativity in long-term survival outcomes in patients with multiple myeloma
.
Blood Adv.
2020
;
4
(
23
):
5988
-
5999
.
9.
Munshi
NC
,
Avet-Loiseau
H
,
Rawstron
AC
, et al
.
Association of minimal residual disease with superior survival outcomes in patients with multiple myeloma: a meta-analysis
.
JAMA Oncol.
2017
;
3
(
1
):
28
-
35
.
10.
Attal
M
,
Lauwers-Cances
V
,
Hulin
C
, et al;
IFM 2009 Study
.
Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma
.
N Engl J Med.
2017
;
376
(
14
):
1311
-
1320
.
11.
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
.
12.
Corre
J
,
Perrot
A
,
Hulin
C
, et al;
Intergroupe Francophone du Myélome (IFM)
.
Improved survival in multiple myeloma during the 2005-2009 and 2010-2014 periods
.
Leukemia.
2021
;
35
(
12
):
3600
-
3603
.
13.
Patel
KK
,
Giri
S
,
Parker
TL
,
Bar
N
,
Neparidze
N
,
Huntington
SF
.
Cost-effectiveness of first-line versus second-line use of daratumumab in older, transplant-ineligible patients with multiple myeloma
.
J Clin Oncol.
2021
;
39
(
10
):
1119
-
1128
.
14.
Facon
T
,
Kumar
SK
,
Plesner
T
, et al
.
Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial
.
Lancet Oncol.
2021
;
22
(
11
):
1582
-
1596
.
15.
Pelligra
CG
,
Parikh
K
,
Guo
S
, et al
.
Cost-effectiveness of pomalidomide, carfilzomib, and daratumumab for the treatment of patients with heavily pretreated relapsed-refractory multiple myeloma in the United States
.
Clin Ther.
2017
;
39
(
10
):
1986
-
2005.e5
.
16.
Carlson
JJ
,
Guzauskas
GF
,
Chapman
RH
, et al
.
Cost-effectiveness of drugs to treat relapsed/refractory multiple myeloma in the United States
.
J Manag Care Spec Pharm.
2018
;
24
(
1
):
29
-
38
.
17.
Gong
CL
,
Studdert
AL
,
Liedtke
M
.
Daratumumab vs pomalidomide for the treatment of relapsed/refractory multiple myeloma: a cost-effectiveness analysis
.
Am J Hematol.
2019
;
94
(
3
):
E68
-
E70
.
18.
Zeng
X
,
Peng
L
,
Peng
Y
,
Tan
C
,
Wan
X
.
Economic evaluation of adding daratumumab to a regimen of bortezomib + dexamethasone in relapsed or refractory multiple myeloma: based on the latest updated analysis of CASTOR
.
Clin Ther.
2020
;
42
(
2
):
251
-
262.e5
.
19.
Zhang
TT
,
Wang
S
,
Wan
N
,
Zhang
L
,
Zhang
Z
,
Jiang
J
.
Cost-effectiveness of daratumumab-based triplet therapies in patients with relapsed or refractory multiple myeloma
.
Clin Ther.
2018
;
40
(
7
):
1122
-
1139
.
20.
Dimopoulos
M
,
Quach
H
,
Mateos
MV
, et al
.
Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study
.
Lancet.
2020
;
396
(
10245
):
186
-
197
.
21.
Stewart
AK
,
Rajkumar
SV
,
Dimopoulos
MA
, et al;
ASPIRE Investigators
.
Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma
.
N Engl J Med.
2015
;
372
(
2
):
142
-
152
.
22.
Dimopoulos
MA
,
Dytfeld
D
,
Grosicki
S
, et al
.
Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma
.
N Engl J Med.
2018
;
379
(
19
):
1811
-
1822
.
23.
San-Miguel
JF
,
Hungria
VT
,
Yoon
SS
, et al
.
Overall survival of patients with relapsed multiple myeloma treated with panobinostat or placebo plus bortezomib and dexamethasone (the PANORAMA 1 trial): a randomised, placebo-controlled, phase 3 trial
.
Lancet Haematol.
2016
;
3
(
11
):
e506
-
e515
.
24.
Richardson
PG
,
Hungria
VT
,
Yoon
SS
, et al
.
Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma: outcomes by prior treatment [published correction appears in Blood. 2016;127(26):3460]
.
Blood.
2016
;
127
(
6
):
713
-
721
.
25.
Yong
K
,
Delforge
M
,
Driessen
C
, et al
.
Multiple myeloma: patient outcomes in real-world practice
.
Br J Haematol.
2016
;
175
(
2
):
252
-
264
.
26.
Sanders
GD
,
Neumann
PJ
,
Basu
A
, et al
.
Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses: second panel on cost-effectiveness in health and medicine
.
JAMA.
2016
;
316
(
10
):
1093
-
1103
.
27.
Shah
GL
,
Winn
AN
,
Lin
PJ
, et al
.
Cost-effectiveness of autologous hematopoietic stem cell transplantation for elderly patients with multiple myeloma using the Surveillance, Epidemiology, and End Results-Medicare Database
.
Biol Blood Marrow Transplant.
2015
;
21
(
10
):
1823
-
1829
.
28.
Olry de Labry Lima
A
,
Gimeno-Ballester
V
,
Ríos Tamayo
R
, et al
.
Cost-effectiveness of lenalidomide maintenance in patients with multiple myeloma who have undergone autologous transplant of hematopoietic progenitor cells
.
Bone Marrow Transplant.
2019
;
54
(
11
):
1908
-
1919
.
29.
Hatswell
AJ
,
Burns
D
,
Baio
G
,
Wadelin
F
.
Frequentist and Bayesian meta-regression of health state utilities for multiple myeloma incorporating systematic review and analysis of individual patient data
.
Health Econ.
2019
;
28
(
5
):
653
-
665
.
30.
Leleu
X
,
Beksac
M
,
Chou
T
, et al
.
Efficacy and safety of weekly carfilzomib (70 mg/m2), dexamethasone, and daratumumab (KdD70) is comparable to twice-weekly KdD56 while being a more convenient dosing option: a cross-study comparison of the CANDOR and EQUULEUS studies
.
Leuk Lymphoma.
2021
;
62
(
2
):
358
-
367
.
31.
Attal
M
,
Richardson
PG
,
Rajkumar
SV
, et al;
ICARIA-MM study group
.
Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study
.
Lancet.
2019
;
394
(
10214
):
2096
-
2107
.
32.
Dimopoulos
MA
,
Terpos
E
,
Boccadoro
M
, et al;
APOLLO Trial Investigators
.
Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial
.
Lancet Oncol.
2021
;
22
(
6
):
801
-
812
.
33.
Chari
A
,
Vogl
DT
,
Gavriatopoulou
M
, et al
.
Oral selinexor-dexamethasone for triple-class refractory multiple myeloma
.
N Engl J Med.
2019
;
381
(
8
):
727
-
738
.
34.
Lonial
S
,
Lee
HC
,
Badros
A
, et al
.
Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study
.
Lancet Oncol.
2020
;
21
(
2
):
207
-
221
.
35.
Bahlis
NJ
,
Dimopoulos
MA
,
White
DJ
, et al
.
Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study
.
Leukemia.
2020
;
34
(
7
):
1875
-
1884
.
36.
Husereau
D
,
Drummond
M
,
Augustovski
F
, et al;
CHEERS 2022 ISPOR Good Research Practices Task Force
.
Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) statement: updated reporting guidance for health economic evaluations
.
BMJ.
2022
;
376
:
e067975
.
37.
Perrot
A
,
Lauwers-Cances
V
,
Cazaubiel
T
, et al
.
Early versus late autologous stem cell transplant in newly diagnosed multiple myeloma: long-term follow up analysis of the IFM 2009 Trial
[abstract].
Blood.
2020
;
136
(
suppl 1
). Abstract 39.
38.
Moreau
P
,
Dimopoulos
MA
,
Mikhael
J
, et al;
IKEMA study group
.
Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial
.
Lancet.
2021
;
397
(
10292
):
2361
-
2371
.
39.
Munshi
NC
,
Anderson
LD
Jr
,
Shah
N
, et al
.
Idecabtagene vicleucel in relapsed and refractory multiple myeloma
.
N Engl J Med.
2021
;
384
(
8
):
705
-
716
.
40.
Berdeja
JG
,
Madduri
D
,
Usmani
SZ
, et al
.
Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study
.
Lancet.
2021
;
398
(
10297
):
314
-
324
.
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