TY - JOUR
T1 - Developments in continuous therapy and maintenance treatment approaches for patients with newly diagnosed multiple myeloma
AU - Dimopoulos, Meletios A.
AU - Jakubowiak, Andrzej J.
AU - McCarthy, Philip L.
AU - Orlowski, Robert Z.
AU - Attal, Michel
AU - Bladé, Joan
AU - Goldschmidt, Hartmut
AU - Weisel, Katja C.
AU - Ramasamy, Karthik
AU - Zweegman, Sonja
AU - Spencer, Andrew
AU - Huang, Jeffrey S.Y.
AU - Lu, Jin
AU - Sunami, Kazutaka
AU - Iida, Shinsuke
AU - Chng, Wee Joo
AU - Holstein, Sarah A.
AU - Rocci, Alberto
AU - Skacel, Tomas
AU - Labotka, Richard
AU - Palumbo, Antonio
AU - Anderson, Kenneth C.
N1 - Funding Information:
The authors acknowledge Steve Hill, Ph.D., of FireKite, an Ashfield company, part of UDG Healthcare plc, for professional medical writing support, which was funded by Millennium Pharmaceuticals Inc, Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, and complied with Good Publication Practice-3 (GPP3) guidelines (Battisti, W. P. et al. Ann. Intern. Med. 163, 461–464 (2015)), and Renda Ferrari, Ph.D. (Millennium Pharmaceuticals, Inc.), for contributing to the editorial and scientific content of the manuscript.
Funding Information:
M.A.D.: Genesis Pharma: Research Funding; Novartis: Consultancy, Honoraria; Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Onyx Pharmaceuticals, an Amgen subsidiary, Takeda Oncology: Consultancy, Honoraria, Other: Advisory Committee. A.J.J.: Consultant and Advisory Boards with honoraria for AbbVie, Amgen, BMS, Celgene, Janssen, Juno, Karyopharm, SkylineDx, Takeda. P.L.M.: honoraria from Celgene, Bristol-Myers Squibb, Sanofi, Takeda, The Binding Site, and Karyopharm Therapeutics; consulting or advisory role for Celgene, Janssen, Bristol-Myers Squibb, Sanofi, and Karyopharm Therapeutics; research funding from Celgene. RZO: research funding from BioTheryX; honoraria from Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Millennium Pharmaceuticals, and Onyx Pharmaceuticals; member of advisory boards for Amgen, Bristol-Myers Squibb, Celgene Corporation, Incyte, Juno, Kite, Legend Biotech, Sanofi-Aventis, and Takeda Pharmaceuticals. M.A.: None. J.B.: honoraria from Janssen, Celgene, Amgen, and Takeda; grant support from Janssen and Celgene. H.G.: advisory boards for Adaptive Biotechnology, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Sanofi, and Takeda; research funding from Amgen, Bristol-Myers Squibb, Celgene, Chugai, Janssen, Sanofi, Mundipharma, Takeda, and Novartis; honoraria from ArtTempi, Bristol-Myers Squibb, Celgene, Chugai, Janssen, and Novartis. K.C.W.: Advisory boards for Amgen, Bristol-Myers Squibb, Adaptive Biotech, Celgene, Janssen, Juno, Takeda, Sanofi; honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen, and Takeda; research funding from Amgen, Celgene, Janssen, and Sanofi. K.R.: Takeda: honoraria, research funding; Amgen: honoraria; Janssen: honoraria; Celgene: honoraria, research funding; Adaptive Biotech: Honoraria; Oncopeptides: Honoraria. S.Z.: research funding from and advisory boards for Takeda, Celgene, and Janssen. A.S.: consultancy for Specialised Therapeutics Australia; honoraria from Takeda, Celgene, Janssen, and Amgen; speaker bureaus for Takeda, Celgene, and Janssen; research funding from Takeda, Celgene, Janssen, and GlaxoSmithKline. J.S.Y.H.: honoraria and advisory boards for Takeda, Celgene, and Janssen. J.L.: None. K.S.: research funding from Takeda, MSD, Celgene, GSK, Novartis, Ono, Janssen, Abbvie, Sanofi, Bristol-Myers Squibb, Alexion-pharma, Diichi-Sankyo; honoraria from Takeda, Celgene, Ono, Bristol-Myers Squibb. S.I.: research funding from Takeda, Ono, Janssen, Celgene, Novartis, Chugai, Abbvie, Bristol-Myers Squibb, Kyowa-Hakko Kirin, Merck Sharp & Dohme, Daiichi Sankyo, Gilead; honoraria from Takeda, Janssen, Celgene, Ono, Daiichi Sankyo, and Bristol-Myers Squibb. W.-J.C.: honoraria from Takeda. S.A.H.: Consultant: Celgene, Sorrento, GSK; Advisory boards: Adaptive Biotechnologies, Takeda. A.R.: Consultancy for Sanofi and Takeda; honoraria from Janssen, Takeda, Celgene, Novartis, Amgen; Advisory board for Novartis, Janssen, Amgen. T.S., R.L., A.P.: Employment, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. T.S.: also affiliated with Department of Hematology, Charles University General Hospital, Prague, Czech Republic. K.C.A.: Membership on an entity’s Board of Directors or advisory committees for Bristol-Myers Squibb, Gilead Sciences, Celgene, Janssen, Sanofi-Aventis, Millennium Pharmaceuticals; Scientific founder: Oncopep, C4 Therapeutics.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - The evolving paradigm of continuous therapy and maintenance treatment approaches in multiple myeloma (MM) offers prolonged disease control and improved outcomes compared to traditional fixed-duration approaches. Potential benefits of long-term strategies include sustained control of disease symptoms, as well as continued cytoreduction and clonal control, leading to unmeasurable residual disease and the possibility of transforming MM into a chronic or functionally curable condition. “Continuous therapy” commonly refers to administering a doublet or triplet regimen until disease progression, whereas maintenance approaches typically involve single-agent or doublet treatment following more intensive prior therapy with autologous stem cell transplant (ASCT) or doublet, triplet, or even quadruplet induction therapy. However, the requirements for agents and regimens within these contexts are similar: treatments must be tolerable for a prolonged period of time, should not be associated with cumulative or chronic toxicity, should not adversely affect patients’ quality of life, should ideally be convenient with a minimal treatment burden for patients, and should not impact the feasibility or efficacy of subsequent treatment at relapse. Multiple agents have been and are being investigated as long-term options in the treatment of newly diagnosed MM (NDMM), including the immunomodulatory drugs lenalidomide and thalidomide, the proteasome inhibitors bortezomib, carfilzomib, and ixazomib, and the monoclonal antibodies daratumumab, elotuzumab, and isatuximab. Here we review the latest results with long-term therapy approaches in three different settings in NDMM: (1) maintenance treatment post ASCT; (2) continuous frontline therapy in nontransplant patients; (3) maintenance treatment post-frontline therapy in the nontransplant setting. We also discuss evidence from key phase 3 trials. Our review demonstrates how the paradigm of long-term treatment is increasingly well-established across NDMM treatment settings, potentially resulting in further improvements in patient outcomes, and highlights key clinical issues that will need to be addressed in order to provide optimal benefit.
AB - The evolving paradigm of continuous therapy and maintenance treatment approaches in multiple myeloma (MM) offers prolonged disease control and improved outcomes compared to traditional fixed-duration approaches. Potential benefits of long-term strategies include sustained control of disease symptoms, as well as continued cytoreduction and clonal control, leading to unmeasurable residual disease and the possibility of transforming MM into a chronic or functionally curable condition. “Continuous therapy” commonly refers to administering a doublet or triplet regimen until disease progression, whereas maintenance approaches typically involve single-agent or doublet treatment following more intensive prior therapy with autologous stem cell transplant (ASCT) or doublet, triplet, or even quadruplet induction therapy. However, the requirements for agents and regimens within these contexts are similar: treatments must be tolerable for a prolonged period of time, should not be associated with cumulative or chronic toxicity, should not adversely affect patients’ quality of life, should ideally be convenient with a minimal treatment burden for patients, and should not impact the feasibility or efficacy of subsequent treatment at relapse. Multiple agents have been and are being investigated as long-term options in the treatment of newly diagnosed MM (NDMM), including the immunomodulatory drugs lenalidomide and thalidomide, the proteasome inhibitors bortezomib, carfilzomib, and ixazomib, and the monoclonal antibodies daratumumab, elotuzumab, and isatuximab. Here we review the latest results with long-term therapy approaches in three different settings in NDMM: (1) maintenance treatment post ASCT; (2) continuous frontline therapy in nontransplant patients; (3) maintenance treatment post-frontline therapy in the nontransplant setting. We also discuss evidence from key phase 3 trials. Our review demonstrates how the paradigm of long-term treatment is increasingly well-established across NDMM treatment settings, potentially resulting in further improvements in patient outcomes, and highlights key clinical issues that will need to be addressed in order to provide optimal benefit.
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U2 - 10.1038/s41408-020-0273-x
DO - 10.1038/s41408-020-0273-x
M3 - Review article
C2 - 32054831
AN - SCOPUS:85079336776
VL - 10
JO - Blood Cancer Journal
JF - Blood Cancer Journal
SN - 2044-5385
IS - 2
M1 - 17
ER -