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Review
. 2022 Dec 27;15(1):155.
doi: 10.3390/cancers15010155.

How to Manage Patients with Lenalidomide-Refractory Multiple Myeloma

Felipe de Arriba de la Fuente  1 , Carmen Montes Gaisán  2 , Javier de la Rubia Comos  3
Affiliations
Review

How to Manage Patients with Lenalidomide-Refractory Multiple Myeloma

Felipe de Arriba de la Fuente et al. Cancers (Basel). .

Abstract

Although lenalidomide-based combinations, such as lenalidomide plus a proteasome inhibitor or an anti-CD38 monoclonal antibody, improve the overall response rate, progression-free survival, and overall survival of patients with relapsed/refractory multiple myeloma (RRMM), there is a tendency to use these regimens as a frontline treatment. This strategy has led to the development of refractoriness early in the disease course, usually after the patient's first treatment. Since lenalidomide-free regimens have so far shown limited efficacy in lenalidomide-refractory patients, there is an unmet need for other treatment options. In this review, we discuss the therapeutic options available to treat the general population of lenalidomide-refractory patients (mono, double and triple refractory) and the subpopulation of patients with other high-risk features such as renal failure, extramedullary disease, and high-risk cytogenetics. Moreover, new promising individual therapies and the possible impact of immunotherapy in RRMM patients are debated.

Keywords: lenalidomide; multiple myeloma; refractory; relapse.

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Conflict of interest statement

F.d.A.d.l.F. has received honoraria from Janssen, Bristol-Myers Squibb-Celgene, Sanofi, Amgen, GlaxoSmithKline, and Takeda; CMG declares no conflicts of interest; JdlRC has served as a consultant and provided expert testimony for AMGEN, BMS, GSK, Janssen, Pfizer, Sanofi, and Takeda. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Available treatments for lenalidomide-refractory MM. Dara: daratumumab; DaraKd: daratumumab plus carfilzomib and dexamethasone; DaraMPV: daratumumab plus melphalan, pomalidomide and bortezomib; DaraPd: daratumumab plus pomalidomide and dexamethasone; DaraVd: daratumumab plus bortezomib and dexamethasone; DaraRd: daratumumab plus lenalidomide and dexamethasone; DCEP: dexamethasone, cyclophosphamide, etoposide, and cisplatin; Dexa-BEAM: dexamethasone, carmustine, cytarabine, etoposide, and melphalan; EloPd: elotuzumab plus pomalidomide and dexamethasone; EloPVd: elotuzumab plus pomalidomide, bortezomib and dexamethasone; IMiD: immunomodulatory drugs; Isa: isatuximab; IsaKd: isatuximab plus carfilzomib and dexamethasone; IsaPd: isatuximab plus pomalidomide and dexamethasone; KCd: carfilzomib plus cyclophosphamide and dexamethasone; Kd: carfilzomib plus dexamethasone; KPd: carfilzomib plus pomalidomide and dexamethasone; PACE: cisplatin, doxorubicin, cyclophosphamide, and etoposide; PI: protease inhibitor; PVd: pomalidomide plus bortezomib and dexamethasone; VdT-PACE: bortezomib plus dexamethasone and thalidomide-cisplatin, doxorubicin, cyclophosphamide, and etoposide.
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