Clinical Hematology International

Volume 2, Issue 2, June 2020, Pages 92 - 93

Bortezomib, Lenalidomide and Dexamethasone as Induction Therapy Prior to Autologous Transplantation in Multiple Myeloma: The More Is Likely the Better

Authors
Mohamad Mohty1, *, ORCID, Florent Malard1, ORCID, Ali Bazarbachi2, 3
1Sorbonne Universités, INSERM, Centre de Recherche Saint-Antoine (CRSA), Hematology Department, AP-HP, Saint Antoine Hospital, Paris, France
2Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
3Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut, Lebanon
*Corresponding author. Email: mohamad.mohty@inserm.fr
Corresponding Author
Mohamad Mohty
Received 24 January 2020, Accepted 7 May 2020, Available Online 18 May 2020.
DOI
10.2991/chi.d.200507.001How to use a DOI?
Copyright
© 2020 International Academy for Clinical Hematology. Publishing services by Atlantis Press International B.V.
Open Access
This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

The autologous hematopoietic cell transplantation (auto-HCT) procedure for multiple myeloma (MM) comprises several key steps: induction, hematopoietic cell mobilization, high-dose chemotherapy followed by hematopoietic cell infusion and posttransplant therapy (including maintenance therapy with or without prior consolidation). For almost 3 decades, the standard induction regimen prior to auto-HCT consisted of 3–4 cycles of vincristine, adriamycin and dexamethasone (historical VAD regimen). The IFM2005-01 randomized trial was the first trial to show the superiority of a novel-agent-based induction (namely bortezomib and dexamethasone, VD) over VAD [1]. The VD regimen served as a backbone to develop triplet induction regimens such as VTD (bortezomib, thalidomide, dexamethasone) [2] or VCD (bortezomib, cyclophosphamide, dexamethasone), both of which were proven to be superior to doublets such as VD or TD (thalidomide and dexamethasone) [2,3]. Of note, another IFM randomized trial could show a slight superiority of VTD over VCD in terms of response rate [4]. Interestingly, none of the aforementioned triplet regimens explored the issue of the number of cycles, and investigators continued to use the classical 3–4 cycles based on the historical VAD experience. However, one must admit, that given the potential serious toxicity of agents such as thalidomide (nonreversible peripheral neuropathy) or cyclophosphamide (cytopenia and its corollary of infectious complications), the issue of the number of cycles of induction prior to auto-HCT was not deemed to be very important by most investigators, especially given the capacity to deliver 2 or 3 cycles of consolidation to deepen the response rate after auto-HCT.

The VRD regimen (bortezomib, lenalidomide, dexamethasone) was initially developed in the relapsed MM setting [5] and proved rapidly to be highly effective with a remarkable safety profile, especially a very low rate of severe peripheral neuropathy when combined to subcutaneous bortezomib. Very rapidly, VRD moved into the frontline setting, and was viewed by most experts as the “standard” induction regimen prior to auto-HCT, since it combines the efficacy of VTD without its added toxicity. The latter positive ratio of efficacy and safety was clearly shown in the trial by Rosinol et al. [6]. In addition, given its good tolerance and feasibility, Rosinol et al. took this regimen a step further, and administered VRD in up to 6 cycles (in contrast to the common historical dogma of 3–4 cycles). The former strategy proved to be highly effective as it allowed for a continuous improvement in the disease response, including achievement of measurable residual disease (MRD) negativity in a substantial number of patients before auto-HCT [6]. These results are of utmost importance, because a deep MRD status is increasingly considered a major goal of MM therapy, because it probably serves as a surrogate marker for improved survival. Overall, the findings from this large Spanish trial will be highly influential and will encourage many investigators to opt for a “longer” induction phase of up to 6 cycles, toxicity allowing.

However, MM therapy is a rapidly evolving field [7,8], and one may wonder how such a “long” induction phase would compare to a quadruplet regimen-based induction administered over a shorter period of time? In this regard, the recent CASSIOPEIA international randomized trial evaluated whether the addition of daratumumab to VTD (Dara-VTD) before (induction) and after auto-HCT (consolidation) would improve the stringent complete response rate in patients with newly diagnosed MM [9]. The latter study showed the clinical benefit of Dara-VTD given in up to 4 cycles as a major regimen for induction in transplant-eligible patients with newly diagnosed MM. As a matter of fact, and given the impressive results of Dara-VTD, it is possible that a Dara-VRD-based induction regimen (currently being tested in prospective trials) will also probably show a significant benefit in this arena. Nevertheless, one should not ignore issues related to cost and access to such quadruplet regimens, though they can also challenge the whole concept of auto-HCT if shown to be feasible over a long period (e.g. a quadruplet regimen administered for one year) and able to induce deep MRD negativity [10]. While waiting for the results of such trials, auto-HCT preceded by a “long” induction with VRD will likely remain a standard of care for many years in many patients across the globe.

CONFLICT OF INTEREST

FM reports lecture honoraria from Therakos/Mallinckrodt, Janssen, Keocyte, Sanofi, JAZZ pharmaceutical and Astellas, all outside the submitted work. MM reports grants and lecture honoraria from Janssen, Sanofi, Maat Pharma and JAZZ pharmaceutical, lecture honoraria from Celgene, Amgen, BMS, Takeda, and Pfizer, grants from Roche. The other authors declare no competing financial interests.

AUTHORS' CONTRIBUTIONS

All authors contributed substantially to the conception, writing, critical review and final approval of the manuscript.

ACKNOWLEDGMENTS

The authors acknowledge the Association for Training, Education and Research in Hematology, Immunology and Transplantation for the generous and continuous support of the research work. We thank our nursing staff for offering the best care to our patients.

Footnotes

Peer review under responsibility of the International Academy for Clinical Hematology

REFERENCES

Journal
Clinical Hematology International
Volume-Issue
2 - 2
Pages
92 - 93
Publication Date
2020/05/18
ISSN (Online)
2590-0048
DOI
10.2991/chi.d.200507.001How to use a DOI?
Copyright
© 2020 International Academy for Clinical Hematology. Publishing services by Atlantis Press International B.V.
Open Access
This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

Cite this article

TY  - JOUR
AU  - Mohamad Mohty
AU  - Florent Malard
AU  - Ali Bazarbachi
PY  - 2020
DA  - 2020/05/18
TI  - Bortezomib, Lenalidomide and Dexamethasone as Induction Therapy Prior to Autologous Transplantation in Multiple Myeloma: The More Is Likely the Better
JO  - Clinical Hematology International
SP  - 92
EP  - 93
VL  - 2
IS  - 2
SN  - 2590-0048
UR  - https://doi.org/10.2991/chi.d.200507.001
DO  - 10.2991/chi.d.200507.001
ID  - Mohty2020
ER  -