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Table of Contents
LETTER TO EDITOR
Year : 2022  |  Volume : 5  |  Issue : 1  |  Page : 186-188

Transplantation and maintenance in multiple myeloma appear to overcome differences in induction regimens


1 Department of Medical Oncology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
2 Department of Immunohematology and Blood Transfusion, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
3 Department of Clinical Hematology and Stem Cell Transplantation, Dayanand Medical College and Hospital, Ludhiana, Punjab, India

Date of Submission16-Nov-2021
Date of Decision14-Dec-2021
Date of Acceptance15-Dec-2021
Date of Web Publication24-Feb-2022

Correspondence Address:
Suvir Singh
Department of Clinical Hematology and Stem Cell Transplantation, Dayanand Medical College and Hospital, Ludhiana - 141 001, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/crst.crst_291_21

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How to cite this article:
Singh J, Joshi K, Singh S. Transplantation and maintenance in multiple myeloma appear to overcome differences in induction regimens. Cancer Res Stat Treat 2022;5:186-8

How to cite this URL:
Singh J, Joshi K, Singh S. Transplantation and maintenance in multiple myeloma appear to overcome differences in induction regimens. Cancer Res Stat Treat [serial online] 2022 [cited 2022 May 21];5:186-8. Available from: https://www.crstonline.com/text.asp?2022/5/1/186/342418



Survival of patients with multiple myeloma has progressively improved over the past decade, with median overall survival (OS) ranging from 40 months to more than 90 months for patients with Stage III and Stage I disease, respectively, according to the revised international staging system.[1] This can be attributed to the introduction of several newer agents, improvement in supportive care, and increased adoption of autologous stem cell transplantation (ASCT) as first-line therapy.[2] In the current era, the treatment paradigm for multiple myeloma consists of induction therapy with a combination of at least three agents, followed by ASCT once a partial response (PR) or better is achieved.

Sidana et al. recently published data from the Center for International Blood and Marrow Transplant Research (CIBMTR) on 1135 patients and compared the outcomes after receiving lenalidomide/bortezomib/dexamethasone (VRD) or bortezomib/cyclophosphamide/dexamethasone (VCD) as induction regimens.[3] The study population was divided into two groups, based on the choice of induction therapy (VRD, n = 914; and VCD, n = 221). Both groups were evenly matched in terms of the disease and patient characteristics. Nearly 100% of the patients demonstrated a demonstrated a PR or better PR or better response after induction, with a slightly higher number of patients achieving a very good PR (VGPR) or better in the VRD arm (65% vs. 59%). The most important finding from the study was the distribution of post-transplant responses, with a similar proportion of patients achieving VGPR or better in both arms (76% vs. 77%). An OS advantage was observed among patients in the VRD arm. On multivariate analysis, maintenance therapy was the only treatment-related factor that impacted survival, with no effect of the induction regimens.

These results provide several important perspectives on the current management of multiple myeloma. First-line induction regimens have gradually evolved over the past decade; this has played an important role in achieving deeper responses, and hence, better survival. Older regimens, including melphalan and prednisolone, were associated with complete response (CR) and VGPR rates of <10%, with the majority of patients achieving only PR.[4] With the introduction of thalidomide, VGPR and CR rates have increased to approximately 25%.[5] Subsequently, the VCD and VRD regimens increased the rates of VGPR or better response to approximately 50%–60%, ensuring better disease control before proceeding to transplant.[6] VRD has been shown to have higher response rates than VCD, ostensibly leading to a greater proportion of patients achieving deeper post-transplant responses. This was also noted in a study from India, in which 125 patients were randomized to receive either VCD or VRD as upfront therapy. Patients receiving VRD demonstrated higher rates of responses, including VGPR (61% vs. 48%) and CR (35% vs. 18%).[7]

However, sequential achievement of deeper responses in myeloma appears to offset any differences in the effect of the initial induction therapy. For instance, in the current CIBMTR study, there was no difference in the proportion of patients achieving a response better than VGPR post-transplantation (86% vs. 89% for VRD vs. VCD, respectively). Relevant to the Indian context, similar findings have been echoed by other studies evaluating transplantation outcomes in myeloma.[8],[9] A study from India confirmed an extreme version of this phenomenon, reporting no differences in post-transplant response rates and OS among patients receiving doublet or triplet induction regimens.[10]

The second important aspect highlighted by these studies is the effect of maintenance therapy. Maintenance therapy with lenalidomide has unequivocally demonstrated an improvement in OS post-transplantation; there is now evidence for its continuous use, rather than stopping it at 2 years.[11],[12] As rightly concluded by the authors, patients on VCD eventually go on to receive lenalidomide as maintenance therapy, which provides similar survival benefits.

Therefore, it would appear that ASCT and maintenance therapy are two of the most significant aspects of myeloma treatment and must be utilized for all eligible patients. This concept will undoubtedly be challenged by newer data, as regimens containing daratumumab demonstrate VGPR or better in over 70% of patients.[13],[14],[15] Until then, VCD and VRD may be considered equal for all practical purposes, and any differences in initial responses can be overcome by ASCT and maintenance therapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, et al. Revised international staging system for multiple myeloma: A report from international myeloma working group. J Clin Oncol 2015;33:2863-9.  Back to cited text no. 1
    
2.
Sneyd MJ, Gray AR, Morison IM. Trends in survival from myeloma, 1990-2015: A competing risks analysis. BMC Cancer 2021;21:821.  Back to cited text no. 2
    
3.
Sidana S, Kumar S, Fraser R, Estrada-Merly N, Giralt S, Agrawal V, et al. Impact of induction therapy with VRD versus VCD on outcomes in patients with multiple myeloma in partial response or better undergoing upfront autologous stem cell transplantation. Transplant Cell Ther 2021;S2666-6367(21)01358-0.  Back to cited text no. 3
    
4.
Mateos MV, Richardson PG, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, et al. Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: Updated follow-up and impact of subsequent therapy in the phase III VISTA trial. J Clin Oncol 2010;28:2259-66.  Back to cited text no. 4
    
5.
Stewart AK, Jacobus S, Fonseca R, Weiss M, Callander NS, Chanan-Khan AA, et al. Melphalan, prednisone, and thalidomide vs. melphalan, prednisone, and lenalidomide (ECOG E1A06) in untreated multiple myeloma. Blood 2015;126:1294-301.  Back to cited text no. 5
    
6.
Moreau P, Hulin C, Macro M, Caillot D, Chaleteix C, Roussel M, et al. VTD is superior to VCD prior to intensive therapy in multiple myeloma: Results of the prospective IFM2013-04 trial. Blood 2016;127:2569-74.  Back to cited text no. 6
    
7.
Kumar L, Chellapuram SK, Sahoo R, Gupta R. VRd versus VCd as induction therapy for newly diagnosed multiple myeloma: A phase III, randomized study. Clin Lymphoma Myeloma Leuk 2019;19:e361.  Back to cited text no. 7
    
8.
Aggarwal M, Agrawal N, Yadav N, Verma P, Ahmed R, Mehta P, et al. Autologous stem cell transplantation in first remission is associated with better progression-free survival in multiple myeloma. Ann Hematol 2018;97:1869-77.  Back to cited text no. 8
    
9.
Malhotra P, Yanamandra U, Khadwal A, Prakash G, Lad D, Law AD, et al. Autologous stem cell transplantation for multiple myeloma: Single centre experience from North India. Indian J Hematol Blood Transfus 2018;34:261-7.  Back to cited text no. 9
    
10.
Kumar L, Gundu N, Kancharia H, Sahoo RK, Malik PS, Sharma A, et al. Multiple myeloma-effect of induction therapy on transplant outcomes. Clin Lymphoma Myeloma Leuk 2021;21:80-90.e5.  Back to cited text no. 10
    
11.
Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med 2012;366:1782-91.  Back to cited text no. 11
    
12.
Dimopoulos MA, Jakubowiak AJ, McCarthy PL, Orlowski RZ, Attal M, Bladé J, et al. Developments in continuous therapy and maintenance treatment approaches for patients with newly diagnosed multiple myeloma. Blood Cancer J 2020;10:17.  Back to cited text no. 12
    
13.
Mateos MV, Dimopoulos MA, Cavo M, Suzuki K, Jakubowiak A, Knop S, et al. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med 2018;378:518-28.  Back to cited text no. 13
    
14.
Bagal B, Bonda A. Induction therapy in newly diagnosed multiple myeloma: Current research scenario and questions for the future. Cancer Res Stat Treat 2019;2:76-82.  Back to cited text no. 14
  [Full text]  
15.
Tandon N, Devadas SK, Khanderia M. Changing landscape of induction therapy in newly diagnosed multiple myeloma. Cancer Res Stat Treat 2019;2:271-2.  Back to cited text no. 15
  [Full text]  




 

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