Blood Res 2023; 58(2):
Published online June 30, 2023
https://doi.org/10.5045/br.2023.2023005
© The Korean Society of Hematology
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.
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.
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
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.
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.
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.
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
Table 1 . Baseline characteristics..
N (%) | VRd (N=37) | D-VTd (N=43) | ||
---|---|---|---|---|
Age at diagnosis | Median, years (range) | 55 (35–65) | 58 (39–70) | 0.010 |
Sex | Male | 21 (56.8) | 22 (51.2) | 0.617 |
ECOG | 0 | 5 (13.5) | 5 (11.6) | 0.096 |
1 | 29 (78.4) | 26 (60.5) | ||
2 | 1 (2.7) | 9 (20.9) | ||
3 | 2 (5.4) | 3 (7.0) | ||
ISS | I | 15 (40.5) | 14 (32.6) | 0.272 |
II | 17 (45.9) | 17 (39.5) | ||
III | 5 (13.5) | 11 (25.6) | ||
Missing | 0 | 1 (2.3) | ||
R-ISS | I | 9 (24.3) | 9 (20.9) | 0.453 |
II | 19 (51.4) | 20 (46.5) | ||
III | 5 (13.5) | 5 (11.6) | ||
Missing | 4 (10.8) | 9 (20.9) | ||
Type | IgG | 24 (64.9) | 22 (51.2) | 0.032 |
IgA | 10 (27.0) | 6 (14.0) | ||
Light chain disease | 3 (8.1) | 14 (32.6) | ||
Non-secretory | 0 | 1 (2.3) | ||
Risk group | High-riska) | 16/34 (47.1) | 11/34 (32.4) | 0.128 |
Missing | 3 | 9 | ||
CrCl | <50 mL/min | 1 (2.7) | 14 (32.6) | 0.001 |
EMD | Present | 9 (24.3) | 10 (23.3) | 0.911 |
Induction cycles | Median (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) | |
---|---|---|---|
Mobilization | 0.625 | ||
G-CSF | 22 (61.1) | 30 (71.4) | |
Chemotherapy | 14 (38.9) | 12 (28.6) | |
Collected cell, CD34×106/kg, mean | 6.9 | 6.4 | 0.556 |
Additional mobilization required | 7 (19.4) | 14 (33.3) | 0.168 |
Induction to ASCT, days, median | 183 | 148 | <0.001 |
ASCT conditioning regimen | |||
HDMEL | 27 (75.0) | 27 (64.3) | 0.036 |
BUMEL | 9 (25.0) | 8 (19.0) | |
MEL140 | 0 | 7 (16.7) | |
Infused cell, CD34×106/kg, mean | 4.3 | 4.1 | 0.449 |
Consolidation after ASCT | 29/35 (82.9) | 5/42 (11.9) | <0.001 |
Tandem ASCT | 0 (0.0) | 1/42 (2.4) | 0.351 |
Maintenance | 9/35 (25.7) | 22/42 (52.4) | 0.014 |
Lenalidomide | 9/9 (100) | 18/22 (81.8) | |
Thalidomide | 0 | 4/22 (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) | ||||
---|---|---|---|---|---|---|
Any | Grade ≥3 | Any | Grade ≥3 | |||
Hematologic AE | ||||||
Neutropenia | 1 (2.7) | 1 (2.7) | 4 (9.3) | 4 (9.3) | 0.224 | |
Thrombocytopenia | 0 | 0 | 0 | 0 | NA | |
Lymphopenia | 1 (2.7) | 0 | 1 (2.3) | 0 | 0.914 | |
Non-hematologic AE | ||||||
Peripheral neuropathy | 11 (29.7) | 0 | 9 (20.9) | 0 | 0.365 | |
Constipation | 12 (32.4) | 1 (2.7) | 12 (27.9) | 0 | 0.660 | |
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) | 0 | 0.058 | |
Edema | 5 (13.5) | 0 | 2 (4.7) | 0 | 0.162 | |
Nausea | 4 (10.8) | 0 | 6 (14.0) | 0 | 0.672 | |
Documented infection | 4 (10.8) | 2 (4.7) | 0.297 | |||
Viral | 2 | 1 | ||||
Bacterial | 2 | 1 | ||||
Fungal | 0 | 0 | ||||
Daratumumab IRR | NA | 19 (44.2%) | 0 | NA | ||
Cycle 1 | 18 | 0 | ||||
Cycle 2 | 0 | 0 | ||||
Cycle 3 | 0 | 0 | ||||
Cycle 4 | 1 | 0 | ||||
IMiD dose reduction | NA | |||||
Lenalidomide | 6 (16.2) | NA | ||||
Thalidomide | NA | 6 (13.6) |
a)
Abbreviations: AE, adverse events; IMiD, immunomodulatory drug; IRR, infusion-related reaction; NA, not applicable..
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