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Original Article

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Blood Res 2023; 58(2):

Published online June 30, 2023

https://doi.org/10.5045/br.2023.2023005

© The Korean Society of Hematology

Advantage of achieving deep response following frontline daratumumab-VTd compared to VRd in transplant-eligible multiple myeloma: multicenter study

Ja Min Byun1#, Sung-Soo Park2#, Sung-Soo Yoon1, Ari Ahn3, Myungshin Kim3, Jung Yeon Lee2, Young-Woo Jeon4, Seung-Hwan Shin5, Seung-Ah Yahng6, Youngil Koh1, Chang-Ki Min2

Author Info. +

1Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 2Department of Hematology, Seoul St. Mary’s Hematology Hospital, College of Medicine, The Catholic University of Korea, 3Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, 4Department of Hematology, Yeoido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 5Department of Hematology, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 6Department of Hematology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea

Correspondence to : Youngil Koh, M.D., Ph.D.
Chang-Ki Min, M.D., Ph.D.
Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea (Y.K.)
Department of Hematology, Seoul St. Mary’s Hematology Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea (C.K.M.)
E-mail: Y.K., go01@snu.ac.kr
C.K.M., ckmin@catholic.ac.kr

#These authors contributed equally and are co-first authors.

Received: January 6, 2023; Revised: March 8, 2023; Accepted: March 28, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Background
The goal of induction therapy for multiple myeloma (MM) is to achieve adequate disease control. Current guidelines favor triplet (bortezomib-lenalidomide-dexamethasone; VRd) or quadruplet regimens (daratumumab, bortezomib-thalidomide-dexamethasone; D-VTd). In the absence of a direct comparison between two treatment regimens, we conducted this study to compare the outcomes and safety of VRd and D-VTd.
Methods
Newly diagnosed MM patients aged ＞18 years who underwent induction therapy followed by autologous stem cell transplantation (ASCT) between November 2020 and December 2021 were identified. Finally, patients with VRd (N=37) and those with D-VTd (N=43) were enrolled.
Results
After induction, 10.8% of the VRd group showed stringent complete remission (sCR), 21.6% showed complete response (CR), 35.1% showed very good partial response (VGPR), and 32.4% showed partial response (PR). Of the D-VTd group, 9.3% showed sCR, 34.9% CR, 48.8% VGPR, and 4.2% PR (VGPR or better: 67.6% in VRd vs. 93% in D-VTd, P=0.004). After ASCT, 68.6% of the VRd group showed CR or sCR, while 90.5% of the D-VTd group showed CR or sCR (P=0.016). VRd was associated with an increased incidence of skin rash (P=0.044). Other than rashes, there were no significant differences in terms of adverse events between the two groups.
Conclusion
Our study supports the use of a front-line quadruplet induction regimen containing a CD38 monoclonal antibody for transplant-eligible patients with newly diagnosed MM.

Graphical Abstract

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Keywords: Transplant-eligible, Newly diagnosed, Quadruplet, Triplet, Multiple myeloma

Article

Original Article

Blood Res 2023; 58(2): 83-90

Published online June 30, 2023 https://doi.org/10.5045/br.2023.2023005

Copyright © The Korean Society of Hematology.

Advantage of achieving deep response following frontline daratumumab-VTd compared to VRd in transplant-eligible multiple myeloma: multicenter study

Ja Min Byun1#, Sung-Soo Park2#, Sung-Soo Yoon1, Ari Ahn3, Myungshin Kim3, Jung Yeon Lee2, Young-Woo Jeon4, Seung-Hwan Shin5, Seung-Ah Yahng6, Youngil Koh1, Chang-Ki Min2

1Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 2Department of Hematology, Seoul St. Mary’s Hematology Hospital, College of Medicine, The Catholic University of Korea, 3Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, 4Department of Hematology, Yeoido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 5Department of Hematology, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 6Department of Hematology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea

Correspondence to:Youngil Koh, M.D., Ph.D.
Chang-Ki Min, M.D., Ph.D.
Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea (Y.K.)
Department of Hematology, Seoul St. Mary’s Hematology Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea (C.K.M.)
E-mail: Y.K., go01@snu.ac.kr
C.K.M., ckmin@catholic.ac.kr

#These authors contributed equally and are co-first authors.

Received: January 6, 2023; Revised: March 8, 2023; Accepted: March 28, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background
The goal of induction therapy for multiple myeloma (MM) is to achieve adequate disease control. Current guidelines favor triplet (bortezomib-lenalidomide-dexamethasone; VRd) or quadruplet regimens (daratumumab, bortezomib-thalidomide-dexamethasone; D-VTd). In the absence of a direct comparison between two treatment regimens, we conducted this study to compare the outcomes and safety of VRd and D-VTd.
Methods
Newly diagnosed MM patients aged ＞18 years who underwent induction therapy followed by autologous stem cell transplantation (ASCT) between November 2020 and December 2021 were identified. Finally, patients with VRd (N=37) and those with D-VTd (N=43) were enrolled.
Results
After induction, 10.8% of the VRd group showed stringent complete remission (sCR), 21.6% showed complete response (CR), 35.1% showed very good partial response (VGPR), and 32.4% showed partial response (PR). Of the D-VTd group, 9.3% showed sCR, 34.9% CR, 48.8% VGPR, and 4.2% PR (VGPR or better: 67.6% in VRd vs. 93% in D-VTd, P=0.004). After ASCT, 68.6% of the VRd group showed CR or sCR, while 90.5% of the D-VTd group showed CR or sCR (P=0.016). VRd was associated with an increased incidence of skin rash (P=0.044). Other than rashes, there were no significant differences in terms of adverse events between the two groups.
Conclusion
Our study supports the use of a front-line quadruplet induction regimen containing a CD38 monoclonal antibody for transplant-eligible patients with newly diagnosed MM.

Keywords: Transplant-eligible, Newly diagnosed, Quadruplet, Triplet, Multiple myeloma

Fig 1.

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Figure 1.Study flow.
Blood Research 2023; 58: 83-90https://doi.org/10.5045/br.2023.2023005

Fig 2.

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Figure 2.Summary of responses and subgroup analysis (A) response throughout the treatment, *VGPR or better rate post induction, 67.6 % vs. 93% (P=0.004); **CR or better rate post ASCT, 68.6% vs. 90.5% (P=0.016); ***MRD negativity at 100 days post ASCT, 66.7% vs. 94.4%, P=0.046, respectively (B) change in response, (C) progression free survival.
Abbreviations: ASCT, autologous stem cell transplantation; CR, complete response; D-VTd, daratumumab-bortezomib-thalidomide-dexame-thasone; MRD, minimal residual disease; PD, progressive disease; PR, partial response; sCR, stringent complete response; VGPR, very good partial response; VRD, bortezomib-lenalidomide-dexam-ethasone.
Blood Research 2023; 58: 83-90https://doi.org/10.5045/br.2023.2023005

Fig 3.

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Figure 3.Daratumumab dose intensity per cycle.
Blood Research 2023; 58: 83-90https://doi.org/10.5045/br.2023.2023005

Table 1 . Baseline characteristics..

N (%)VRd (N=37)D-VTd (N=43)P
Age at diagnosisMedian, years (range)55 (35–65)58 (39–70)0.010
SexMale21 (56.8)22 (51.2)0.617
ECOG05 (13.5)5 (11.6)0.096
129 (78.4)26 (60.5)
21 (2.7)9 (20.9)
32 (5.4)3 (7.0)
ISSI15 (40.5)14 (32.6)0.272
II17 (45.9)17 (39.5)
III5 (13.5)11 (25.6)
Missing01 (2.3)
R-ISSI9 (24.3)9 (20.9)0.453
II19 (51.4)20 (46.5)
III5 (13.5)5 (11.6)
Missing4 (10.8)9 (20.9)
TypeIgG24 (64.9)22 (51.2)0.032
IgA10 (27.0)6 (14.0)
Light chain disease3 (8.1)14 (32.6)
Non-secretory01 (2.3)
Risk groupHigh-riska)16/34 (47.1)11/34 (32.4)0.128
Missing39
CrCl<50 mL/min1 (2.7)14 (32.6)0.001
EMDPresent9 (24.3)10 (23.3)0.911
Induction cyclesMedian (range)5 (1–6)4 (2–5)<0.001

a)High-risk multiple myeloma: presence of del(17p) and/or t(4, 14) and/or t(14, 16) translocations..

Abbreviations: CrCl, creatinine clearance; ECOG, Eastern Cooperative Oncology Group; EMD, extramedullary disease; ISS, International Staging System; NA, not applicable; R-ISS, Revised International Staging System..

Table 2 . ASCT and post-ASCT treatment details..

N (%)VRd (N=36)D-VTd (N=42)P
Mobilization0.625
G-CSF22 (61.1)30 (71.4)
Chemotherapy14 (38.9)12 (28.6)
Collected cell, CD34×106/kg, mean6.96.40.556
Additional mobilization required7 (19.4)14 (33.3)0.168
Induction to ASCT, days, median183148<0.001
ASCT conditioning regimen
HDMEL27 (75.0)27 (64.3)0.036
BUMEL9 (25.0)8 (19.0)
MEL14007 (16.7)
Infused cell, CD34×106/kg, mean4.34.10.449
Consolidation after ASCT29/35 (82.9)5/42 (11.9)<0.001
Tandem ASCT0 (0.0)1/42 (2.4)0.351
Maintenance9/35 (25.7)22/42 (52.4)0.014
Lenalidomide9/9 (100)18/22 (81.8)
Thalidomide04/22 (18.2)

Abbreviations: ASCT, autologous stem cell transplantation; BUMEL, busulfan plus melphalan; G-CSF, granulocyte colony-stimulating factor; HDMEL, high-dose melphalan or melphalan 200 mg/m2; MEL140, melphalan 140 mg/m2..

Table 3 . Adverse events..

N (%)VRd (N=37)D-VTd (N=43)Pa)
AnyGrade ≥3AnyGrade ≥3
Hematologic AE
Neutropenia1 (2.7)1 (2.7)4 (9.3)4 (9.3)0.224
Thrombocytopenia0000NA
Lymphopenia1 (2.7)01 (2.3)00.914
Non-hematologic AE
Peripheral neuropathy11 (29.7)09 (20.9)00.365
Constipation12 (32.4)1 (2.7)12 (27.9)00.660
Skin rashb)11 (29.7)3 (8.1)5 (11.6)1 (2.3)0.044
Pruritisc)8 (21.6)1 (2.7)3 (7.0)00.058
Edema5 (13.5)02 (4.7)00.162
Nausea4 (10.8)06 (14.0)00.672
Documented infection4 (10.8)2 (4.7)0.297
Viral21
Bacterial21
Fungal00
Daratumumab IRRNA19 (44.2%)0NA
Cycle 1180
Cycle 200
Cycle 300
Cycle 410
IMiD dose reductionNA
Lenalidomide6 (16.2)NA
ThalidomideNA6 (13.6)

a)P-value for adverse events. b)P-value for grade ≥3 skin rash, P=0.237. c)P-value for grade ≥3 pruritis, P=0.278..

Abbreviations: AE, adverse events; IMiD, immunomodulatory drug; IRR, infusion-related reaction; NA, not applicable..
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