Journal Information
Vol. 41. Issue 4.
Pages 283-284 (October - December 2019)
Share
Share
Download PDF
More article options
Vol. 41. Issue 4.
Pages 283-284 (October - December 2019)
Scientific Comment
DOI: 10.1016/j.htct.2019.09.001
Open Access
Induction therapy and stem-cell mobilization in myeloma, look at the past to plan the future
Visits
...
Rony Schaffel
Corresponding author
rony@hucff.ufrj.br

Corresponding author at: Universidade Federal do Rio de Janeiro, Hospital Universitário Clementino Fraga Filho. Rua Rodolpho Paulo Rocco, 255 - Ilha do Fundão, sala 4A12 Serviço de Hematologia Ilha do Fundão, CEP: 21941590, Rio de Janeiro, RJ, Brazil.
Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
Related content
hematol Transfus Cell Ther. 2019;41:285-9110.1016/j.htct.2019.03.005
Amarilis Figueiredo, Rabih Kassis, Rashed Albacker, Arleigh McCurdy, Natasha Kekre, Harold Atkins
Article information
Full Text
Bibliography
Download PDF
Statistics
Full Text

High-dose chemotherapy and autologous stem-cell transplant (ASCT) remains the standard of care for first-line therapy in eligible patients with symptomatic multyple myeloma. This is quite remarkable given the number of new drugs incorporated in myeloma therapy after the classical Attal et al. manuscript published 25 years ago showing the superiority of ASCT (using melphalan and TBI and bone marrow as stem-cell source) over an outdated chemotherapy regimen (VMCP-VBAP).1 This superiority still stands out as shown by the 2019 ASCO report of the FORTE trial when ASCT reduced the risk of early relapse in high-risk patients treated with the triplet carfilzomib, lenalidomide, dexamethasone.2 Currently, multiple myeloma is the leading indication of ASCT with more than 9000 patients reported to the CIBMTR in 2017.3

Complete remission after ASCT has been shown to be predictive of better progression-free survival and overall survival.4 The disease status after induction therapy and before ASCT is very important as well and more potent combinations are favored.5,6 Moreover, there is a growing tendency to analyse the impact of clinical trials results in relation of real world data because of the tendency to include younger and fitter patients in clinical trials.7

This is the landscape where the article from Figueiredo et al. fits in.8 The analysis of 472 patients with myeloma included in an ASCT program for more then two decades enable them to show the difference in stem-cell collection efficiency comparing older induction treatments such as VAD (most popular before 2005) and botezomib-based combinations still being used today. Their main finding was that therapy with bortezomib-dexamethasone (BD) was associated with the collection of a higher median number of CD34+ cells/Kg, less failures, less number of apheresis and a better safety-profile than VAD or bortezomib-cyclophosphamide-dexamethasone (CyBorD) therapies. This is in line with other studies such as Musto et al. that evaluated 1348 patients with myeloma and showed that hematological toxicity of the induction therapy, which is higher for CyBorD, was the most importante adverse prognostic factor for stem-cell collection.9

Those findings should be viewed with great caution as triplets, such as CyBorD or VTD, are the standard of care for induction therapy in myeloma patients eligilble for ASCT.6 As a real-world study, the induction therapy was part of the center’s policy and both BD and CyBorD were used during the same period (between 2010 and 2015). Although they showed that the groups were similar in terms of general baseline conditions, the only way to avoid a selection bias would have been the randomization of the patients. Moreover, poor mobilization prognostic factors such as prior radiotherapy, baseline cytopenias and disease response after induction were not compared. Other important features such as baseline cytogenetic risk were not informed.

Almost all the patients were mobilized with variable-dose cyclophosphamide and filgrastim and this had no impact in disease response before high-dose chemotherapy. Given this finding, filgastrim-only mobilization may be a better strategy because it is more predictable and less toxic specially with a preemptive plerixafor strategy.

Given the large time-span of the study it would have been interesting to know if different practices before and after the transplant in the real-world setting would translate into the same outcomes as those reported in the clinical trials. Unfortunately, no survival curve was generated probably because most patients go back to the referral centers and the contact is lost. This information woud add a lot to the study specially considering the comparison between BD (good mobilization but less effective) and CyBorD patients which seem to have comparable follow up.

We are constantly being exposed to clinical trials designed with the aim to test new drugs specially in the myeloma field. In general, follow up is relatively short and outcomes such as response or progression-free survival are being favored over overall survival. Those trials are very importante because myeloma is still a very difficult disease in 2019. However, studies such as the one presented by Figueiredo et al. are of comparable importance because they can provide the information regarding external validity of the different therapies over a longer period of time. Look at the past is the way to reassure our present and make changes for the future.

Conflicts of interest

The authors declare no conflicts of interest.

References
[1]
M. Attal, J.L. Harousseau, A.M. Stoppa, J.J. Sotto, J.G. Fuzibet, J.F. Rossi, et al.
A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome.
N Engl J Med, 335 (1996), pp. 91-97
[2]
F. Gay, C. Cerrato, D.R. Scalabrini, A. Belotti, M. Galli, E. Zamagni, et al.
Carfilzomib lenalidomide dexamethasone (krd) with or without transplantation in newly diagnosed myeloma (forte trial): efficacy according to risk status.
Eha Library, 267455 (2019), pp. S872
[3]
D’Souza A, Fretham C. Current Uses and Outcomes of Hematopoietic Cell Transplantation (HCT): CIBMTR Summary Slides, 2018 [Internet]. Available from: https://www.cibmtr.org.
[4]
N. Lehners, N. Becker, A. Benner, M. Pritsch, M. Löpprich, E. Karl Mai, et al.
Analysis of long‐term survival in multiple myeloma after first-line autologous stem cell transplantation: impact of clinical risk factors and sustained response.
Cancer Med, 7 (2018), pp. 307-316
[5]
J.S. Kim, K. Kim, J.W. Cheong, Y.H. Min, C. Suh, H. Kim, et al.
Korean Multiple Myeloma Working Party. Complete remission status before autologous stem cell transplantation is an important prognostic factor in patients with multiple myeloma undergoing upfront single autologous transplantation.
Biol Blood Marrow Transplant, 15 (2009), pp. 463-470
[6]
P. Moreau, C. Hulin, M. Macro, D. Caillot, C. Chaleteix, M. Roussel, et al.
VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospective IFM2013-04 trial.
Blood, 127 (2016), pp. 2569-2574
[7]
K. Bergin, Z. McQuilten, E. Moore, E. Wood, A. Spencer.
Myeloma in the real world: what is really happening?.
Clin Lymphoma Myeloma Leuk, 17 (2017), pp. 133-144
[8]
A. Figueiredo, R. Kassis, R. Albacker, A. McCurdy, N. Kekre, H. Atkins.
The impact of multiple myeloma induction therapy on hematopoietic stem cell mobilization and collection: 25-year experience.
Hematol Transfus Cell Ther., 41 (2019), pp. 285-291
[9]
P. Musto, V. Simeon, A. Grossi, F. Gay, S. Bringhen, A. Larocca, et al.
Predicting poor peripheral blood stem cell collection in patients with multiple myeloma receiving pre-transplant induction therapy with novel agents and mobilized with cyclophosphamide plus granulocyte-colony stimulating factor: results from a Gruppo Italiano Malattie EMatologiche dell’Adulto Multiple Myeloma Working Party study.
Stem Cell Res Ther, 6 (2015), pp. 64

Please cite this article as: Schaffel R. Induction therapy and stem-cell mobilization in myeloma, look at the past to plan the future. Hematol Transfus Cell Ther. https://doi.org/10.1016/j.htct.2019.09.001

Copyright © 2019. Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular
Idiomas
Hematology, Transfusion and Cell Therapy

Subscribe to our newsletter

Article options
Tools
en pt
Cookies policy Política de cookies
To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here. Utilizamos cookies próprios e de terceiros para melhorar nossos serviços e mostrar publicidade relacionada às suas preferências, analisando seus hábitos de navegação. Se continuar a navegar, consideramos que aceita o seu uso. Você pode alterar a configuração ou obter mais informações aqui.