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Review
. 2018 Jan;78(1):19-37.
doi: 10.1007/s40265-017-0841-y.

Current and New Therapeutic Strategies for Relapsed and Refractory Multiple Myeloma: An Update

Inger S Nijhof  1 , Niels W C J van de Donk  2 , Sonja Zweegman  2 , Henk M Lokhorst  2
Affiliations
Review

Current and New Therapeutic Strategies for Relapsed and Refractory Multiple Myeloma: An Update

Inger S Nijhof et al. Drugs. 2018 Jan.

Abstract

Although survival of multiple myeloma patients has at least doubled during recent years, most patients eventually relapse, and treatment at this stage may be particularly complex. At the time of relapse, the use of alternative drugs to those given upfront is current practice. However, many new options are currently available for the treatment of relapsed multiple myeloma, including recently approved drugs, such as the second- and third-generation proteasome inhibitors carfilzomib and ixazomib, the immunomodulatory agent pomalidomide, the monoclonal antibodies daratumumab and elotuzumab and the histone deacetylase inhibitor panobinostat, but also new targeted agents are under active investigation (e.g. signal transduction modulators, kinesin spindle protein inhibitors, and inhibitors of NF-kB, MAPK, AKT). We here describe a new paradigm for the treatment of relapsed multiple myeloma. The final goal should be finding a balance among efficacy, toxicity, and cost and, at the end of the road, achieving long-lasting control of the disease and eventually even cure in a subset of patients.

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Conflict of interest statement

Funding

No funding was received for the preparation of this manuscript. Open Access was funded by the Springer Compact agreement with the Association of Dutch Universities.

Conflicts of interest

ISN: no conflicts exist. NvdD: research funding (Janssen, Celgene, Amgen, Novartis and BMS) and advisory board (Janssen, Celgene, Amgen, BMS and Novartis); SZ.: research funding (Janssen, Celgene, Takeda) and advisory board (Takeda, Janssen, Celgene and Novartis); HL: research funding (Genmab, Janssen), and advisory board (Janssen, Takeda, Amgen).

Figures

Fig. 1
Fig. 1
Factors influencing choice of therapy at relapse. LDH lactodehydrogenase, DVT deep venous thrombosis, PNP polyneuropathy, HDT-ASCT high-dose therapy-autologous stem cell transplantation, IMiDs immunomodulatory drugs, PIs proteasome inhibitors
Fig. 2
Fig. 2
Treatment recommendations for transplant eligible patients (or young, fit patients). PI, proteasome inhibitor; IMiD, immunomodulatory drugs; DRd, daratumumab-lenalidomide-daratumumab; KRd, carfilzomib-lenalidomide-dexamethasone; IRd, ixazomib-lenalidomide-dexamethasone; ERd, elotuzumab-lenalidomide-dexamethasone; DVd, daratumumab-bortezomib-daratumumab; PanoVd, panobinostat-bortezomib-dexamethasone; VTd, bortezomib-thalidomide-dexamethasone; VCd, bortezomib-cyclophosphamide-dexamethasone; VRD, bortezomib-lenalidomide-dexamethasone; Rad, lenalidomide-adriamycine-dexamethasone; RD, lenalidomide-dexamethasone; Vd, bortezomib-dexamethasone; Kd, carfilzomib-dexamethasone; PR, partial response; HDT-ASCT, high dose therapy-autologous stem cell transplantation; allo-SCT, allogeneic stem cell transplantation. 1 Allo-SCT may be considered in young, fit patients; only as part of clinical trial
Fig. 3
Fig. 3
Treatment recommendations for transplant ineligible patients. PI, proteasome inhibitor; IMiD, immunomodulatory drugs; dara, daratumumab; PR, partial response; RRMM, relapsed and/or refractory multiple myeloma; REP, lenalidomide-cyclophosphamide-prednisone; PCd, pomalidomide-cyclophosphamide-dexamethasone; PCP, pomalidomide-cyclophosphamide-prednisone
See this image and copyright information in PMC

References

    1. Anderson KC. The 39th David A. Karnofsky lecture: bench-to-bedside translation of targeted therapies in multiple myeloma. J Clin Oncol. 2012;30:445–452. doi: 10.1200/JCO.2011.37.8919. - DOI - PMC - PubMed
    1. Barosi G, Merlini G, Billio A, Boccadoro M, Corradini P, Marchetti M, Massaia M, Tosi P, Palumbo A, Cavo M, Tura S. SIE, SIES, GITMO evidence-based guidelines on novel agents (thalidomide, bortezomib, and lenalidomide) in the treatment of multiple myeloma. Ann Hematol. 2012;91:875–888. doi: 10.1007/s00277-012-1445-y. - DOI - PubMed
    1. Kumar SK, Dimopoulos MA, Kastritis E, et al. Natural history of relapsed myeloma, refractory to immunomodulatory drugs and proteasome inhibitors: a multicenter IMWG study. Leukemia. 2017;31(11):2443–2448. doi: 10.1038/leu.2017.138. - DOI - PubMed
    1. Keats JJ, Chesi M, Egan JB, et al. Clonal competition with alternating dominance in multiple myeloma. Blood. 2012;120:1067–1076. doi: 10.1182/blood-2012-01-405985. - DOI - PMC - PubMed
    1. Bolli N, Avet-Loiseau H, Wedge DC, et al. Heterogeneity of genomic evolution and mutational profiles in multiple myeloma. Nat Commun. 2014;5:2997. doi: 10.1038/ncomms3997. - DOI - PMC - PubMed

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