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Review
. 2019 Jan;98(1):1-18.
doi: 10.1007/s00277-018-3546-8. Epub 2018 Nov 23.

Navigating the treatment landscape in multiple myeloma: which combinations to use and when?

Hartmut Goldschmidt  1 , John Ashcroft  2 , Zsolt Szabo  3 , Laurent Garderet  4   5
Affiliations
Review

Navigating the treatment landscape in multiple myeloma: which combinations to use and when?

Hartmut Goldschmidt et al. Ann Hematol. 2019 Jan.

Abstract

Multiple myeloma is one of the most common hematological malignancies, affecting mainly elderly patients. The treatment landscape for the management of this disease has evolved significantly over the past 15 years, and a vast array of therapeutics is now available, including immunomodulatory drugs, proteasome inhibitors, histone deacetylase inhibitors, and monoclonal antibodies. As a result, deciding which drugs to use and when, and whether these should be used in a particular order or combination, can be challenging. Although combination regimens are often associated with deeper responses and better long-term outcomes than monotherapy, and are becoming the standard of care, they may result in significant incremental toxicity; hence, a sequential approach may be more appropriate for some patients. In particular, treatment choices can vary depending on whether the patient has newly diagnosed multiple myeloma, is eligible for transplant, has relapsed and/or refractory multiple myeloma, or is considered to have high-risk disease. In this review, we discuss factors to be taken into account when making treatment decisions in each of these settings. We also briefly discuss possible therapeutic strategies involving agents that may become available in the future.

Keywords: Combination therapy; Multiple myeloma; Sequential therapy; Treatment regimen.

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Conflict of interest statement

HG has received research support from Bristol-Myers Squibb, Celgene Ltd., Chugai, Janssen, Millenium Pharmaceuticals, Inc., and Novartis International AG, has participated in advisory boards for Amgen, Bristol-Myers Squibb, Celgene Ltd., Janssen, Novartis International AG, Onyx Pharmaceuticals, Inc., and Takeda, and has received honoraria from Celgene Ltd., Chugai, Janssen, Millenium Pharmaceuticals, Inc., Novartis International AG, and Onyx Pharmaceuticals, Inc. JA has participated in advisory boards and as a consultant for Amgen, Celgene Ltd., Janssen, and Takeda. ZS is an employee of Amgen and holds stock. LG is a consultant for Amgen, Novartis International AG, and Takeda.

Figures

Fig. 1
Fig. 1
Treatment algorithm for patients with newly diagnosed multiple myeloma. ASCT, autologous stem cell transplantation; CD, cyclophosphamide and dexamethasone; CPR, cyclophosphamide, prednisone, and lenalidomide; CTD, cyclophosphamide, thalidomide, and dexamethasone; MM, multiple myeloma; MP, melphalan and prednisone; MPR, melphalan, prednisone, and lenalidomide; MPR-R, melphalan, prednisone, and lenalidomide, with lenalidomide maintenance; MPT, melphalan, prednisone, and thalidomide; PAD, bortezomib, doxorubicin, and dexamethasone; Rd, lenalidomide and low-dose dexamethasone; RD, lenalidomide and high-dose dexamethasone; VCD, bortezomib, cyclophosphamide, and dexamethasone; VD, bortezomib and dexamethasone; VMP, bortezomib, melphalan, and prednisone; VMPT-VT, bortezomib, melphalan, prednisone, and thalidomide, with bortezomib and thalidomide maintenance; VRd, lenalidomide, bortezomib, and low-dose dexamethasone; VRD, bortezomib, lenalidomide, and dexamethasone; VTD, bortezomib, thalidomide, and dexamethasone. aTherapies approved by the European Medicines Agency
Fig. 2
Fig. 2
Treatment algorithm for patients with relapsed/refractory multiple myeloma. ASCT, autologous stem cell transplantation; CRD, cyclophosphamide, lenalidomide, and dexamethasone; CTD, cyclophosphamide, thalidomide, and dexamethasone; IMiD, immunomodulatory drug; IxRd, ixazomib, lenalidomide, and low-dose dexamethasone; Kd, carfilzomib and low-dose dexamethasone; KRd, carfilzomib, lenalidomide, and low-dose dexamethasone; MM, multiple myeloma; MPT, melphalan, prednisone, and thalidomide; PAD, bortezomib, doxorubicin, and dexamethasone; PanVD, panobinostat, bortezomib, and dexamethasone; PomD, pomalidomide and dexamethasone; Rd, lenalidomide and low-dose dexamethasone; RD, lenalidomide and high-dose dexamethasone; TD, thalidomide and dexamethasone; TFI, treatment-free interval; VCD, bortezomib, cyclophosphamide, and dexamethasone; V ± D, bortezomib with or without dexamethasone; VMP, bortezomib, melphalan, and prednisone; V/PLD, bortezomib and pegylated liposomal doxorubicin; VRD, bortezomib, lenalidomide, and dexamethasone; VTD, bortezomib, thalidomide, and dexamethasone. aTherapies approved by the European Medicines Agency
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