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Review
. 2023 Apr 5;15(7):2160.
doi: 10.3390/cancers15072160.

Management of Relapsed-Refractory Multiple Myeloma in the Era of Advanced Therapies: Evidence-Based Recommendations for Routine Clinical Practice

Danai Dima  1 , Fauzia Ullah  1 , Sandra Mazzoni  1 , Louis Williams  1 , Beth Faiman  1 , Austin Kurkowski  2 , Chakra Chaulagain  3 , Shahzad Raza  1 , Christy Samaras  1 , Jason Valent  1 , Jack Khouri  1 , Faiz Anwer  1
Affiliations
Review

Management of Relapsed-Refractory Multiple Myeloma in the Era of Advanced Therapies: Evidence-Based Recommendations for Routine Clinical Practice

Danai Dima et al. Cancers (Basel). .

Abstract

Multiple myeloma (MM) is the second most common hematologic malignancy in adults worldwide. Over the past few years, major therapeutic advances have improved progression-free and overall survival, as well as quality of life. Despite this recent progress, MM remains incurable in the vast majority of cases. Patients eventually relapse and become refractory to multiple drug classes, making long-term management challenging. In this review, we will focus on the treatment paradigm of relapsed/refractory MM (RRMM) in the era of advanced therapies emphasizing the available novel modalities that have recently been incorporated into routine practice, such as chimeric antigen receptor T-cell therapy, bispecific antibodies, and other promising approaches. We will also discuss major factors that influence the selection of appropriate drug combinations or cellular therapies, such as relapse characteristics, and other disease and patient related parameters. Our goal is to provide insight into the currently available and experimental therapies for RRMM in an effort to guide the therapeutic decision-making process.

Keywords: CAR-T cell therapy; autologous stem cell transplant; bispecific antibodies; immunomodulators; immunotherapy; proteasome inhibitors; relapsed/refractory multiple myeloma; targeted therapy.

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Conflict of interest statement

Shahzad Raza—advisory board—Kite, Incyte. Faiz Anwer: Bristol Myers Squibb (consultancy, research funding and speakers bureau), Janssen (consultancy), Allogene Therapeutics (research funding). Jason Valent: Alexion, AstraZeneca Rare Disease (research funding). The other authors do not have any financial or non-financial potential conflicts of interest.

Figures

Figure 1
Figure 1
Mechanisms of action of available drug classes used in relapsed/refractory MM. Abbreviations: BsAbs, bispecific antibodies; BiTE, bispecific T-cell engager; ADC, antibody drug conjugate; IMiD, immunomodulatory drug; ADCC, antibody dependent cell cytotoxicity; ADCP, antibody dependent cellular phagocytosis; CDC, complement dependent cytotoxicity; MAC, membrane attack complex; CAR, chimeric antigen receptor; BCL-2, B-cell leukemia/lymphoma 2 protein; CRBN, cereblon; NE, nuclear export.
Figure 2
Figure 2
Management of MM at first relapse. Abbreviations: Cy, cyclophosphamide; Dara, daratumumab; d, dexamethasone; Elo, elotuzumab; Isa, isatuximab; V, bortezomib; K, carfilzomib; I, ixazomib; R, lenalidomide; P, pomalidomide; AHCT, autologous hematopoietic cell transplant.
Figure 3
Figure 3
Management of MM at second or later relapse. Abbreviations: Cy, cyclophosphamide; Dara, daratumumab; d, dexamethasone; Elo, elotuzumab; Isa, isatuximab; V, bortezomib; K, carfil zomib; I, ixazomib; R, lenalidomide; P, pomalidomide; BM, bendamustine; Sel, selinexor; Ven, venetoclax.
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