Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jan 9;10(1):1.
doi: 10.1186/s40364-021-00344-2.

The changing landscape of relapsed and/or refractory multiple myeloma (MM): fundamentals and controversies

José-Ángel Hernández-Rivas  1 , Rafael Ríos-Tamayo  2 , Cristina Encinas  3 , Rafael Alonso  4 , Juan-José Lahuerta  5
Affiliations
Review

The changing landscape of relapsed and/or refractory multiple myeloma (MM): fundamentals and controversies

José-Ángel Hernández-Rivas et al. Biomark Res. .

Abstract

The increase in the number of therapeutic alternatives for both newly diagnosed and relapsed/refractory multiple myeloma (RRMM) patients has widened the clinical scenario, leading to a level of complexity that no algorithm has been able to cover up to date. At present, this complexity increases due to the wide variety of clinical situations found in MM patients before they reach the status of relapsed/refractory disease. These different backgrounds may include primary refractoriness, early relapse after completion of first-line therapy with latest-generation agents, or very late relapse after chemotherapy or autologous transplantation. It is also important to bear in mind that many patient profiles are not fully represented in the main randomized clinical trials (RCT), and this further complicates treatment decision-making. In RRMM patients, the choice of previously unused drugs and the number and duration of previous therapeutic regimens until progression has a greater impact on treatment efficacy than the adverse biological characteristics of MM itself. In addition to proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies and corticosteroids, a new generation of drugs such as XPO inhibitors, BCL-2 inhibitors, new alkylators and, above all, immunotherapy based on conjugated anti-BCMA antibodies and CAR-T cells, have been developed to fight RRMM. This comprehensive review addresses the fundamentals and controversies regarding RRMM, and discusses the main aspects of management and treatment. The basis for the clinical management of RRMM (complexity of clinical scenarios, key factors to consider before choosing an appropriate treatment, or when to treat), the arsenal of new drugs with no cross resistance with previously administered standard first line regimens (main phase 3 clinical trials), the future outlook including the usefulness of abandoned resources, together with the controversies surrounding the clinical management of RRMM patients will be reviewed in detail.

Keywords: Immunomodulatory drugs; Monoclonal antibodies; Multiple myeloma; New agents; Proteasome inhibitors; Refractory; Relapsed.

PubMed Disclaimer

Conflict of interest statement

J-A.H-R. reports advisory and consultancy honoraria from Janssen, BMS/Celgene, Amgen, Takeda, GlaxoSmithKline and Sanofi. R.A. has served in a consultancy role or served on a speaker’s bureau for and received honoraria from Celgene/BMS, Janssen, Amgen, Sanofi, GlaxoSmithKline and Pfizer. C.E. reports received honoraria from lectures and advisory boards from Janssen, Celgene/BMS, Amgen, Sanofi, Takeda and GlaxoSmithKline. R.R-T. reports advisory and consultancy from Amgen, Becton Dickinson, Binding Site, Celgene, Janssen, Sanofi, and Takeda. J.J.L. has served in a consultancy role or served on a speaker’s bureau for Celgene/BMS, Takeda, Amgen, Janssen-Cilag, Sanofi, GlaxoSmithKline and received expenses for travel and accommodations from Celgene/BMS.

References

    1. Dimopoulos MA, Moreau P, Terpos E, Mateos MV, Zweegman S, Cook G, et al. Multiple Myeloma: EHA-ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up. Hemasphere. 2021;5(2):e528. - PMC - PubMed
    1. Gulla A, Anderson KC. Multiple myeloma: the (r) evolution of current therapy and a glance into future. Haematologica. 2020;105(10):2358–2367. - PMC - PubMed
    1. Durer C, Durer S, Lee S, Chakraborty R, Malik MN, Rafae A, et al. Treatment of relapsed multiple myeloma: Evidence-based recommendations. Blood Rev. 2020;39:100616. - PubMed
    1. Barlogie B, Smith L, Alexanian R. Effective treatment of advanced multiple myeloma refractory to alkylating agents. N Engl J Med. 1984;310(21):1353–1356. - PubMed
    1. Cook G, Ashcroft AJ, Cairns DA, Williams CD, Brown JM, Cavenagh JD, et al. The effect of salvage autologous stem-cell transplantation on overall survival in patients with relapsed multiple myeloma (final results from BSBMT/UKMF Myeloma X Relapse [Intensive]): a randomised, open-label, phase 3 trial. Lancet Haematol. 2016;3(7):e340–e351. - PubMed