Thalidomide and lenalidomide: Mechanism-based potential drug combinations

  title={Thalidomide and lenalidomide: Mechanism-based potential drug combinations},
  author={Sonia Vallet and Antonio Palumbo and Noopur S. Raje and Mario Boccadoro and Kenneth C. Anderson},
  journal={Leukemia \& Lymphoma},
  pages={1238 - 1245}
Thalidomide and its analogue lenalidomide are potent anti-inflammatory, anti-angiogenic and immunomodulatory drugs, successfully used for the treatment of hematological cancers, in particular multiple myeloma (MM). Both drugs reveal a dual mechanism of action: they target tumour cells by direct cytotoxicity and, indirectly, by interfering with several components of the bone marrow microenvironment. Lenalidomide and thalidomide are versatile drugs with a broad range of activities that potentiate… 

Treatment of Hematologic Neoplasms with New Immunomodulatory Drugs (IMiDs)

  • P. Wiernik
  • Medicine
    Current treatment options in oncology
  • 2009
The data suggest that thalidomide analogs will play a major role in the management of certain hematologic neoplasms in the near future.

Future directions in immunomodulatory therapy

  • S. Lonial
  • Medicine, Biology
    Medical oncology
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Clinical development of immunomodulatory agents should continue to be based on preclinical rationale, which has resulted in a number of promising and clinically active combinations.

Therapeutic effects of thalidomide in hematologic disorders: a review

Thalidomide's therapeutic effects in hematology is reviewed, including those on multiple myeloma, Waldenstroem macroglobulinemia, lymphomas, mantle-cell lymphoma, myelodysplastic syndrome, hereditary hemorrhagic telangiectasia, and graftversus-host disease.

Novel Agents for Relapsed and/or Refractory Multiple Myeloma

Combinations of novel agents with each other and/or traditional chemotherapeutics have vastly increased the treatment options for patients both frontline, and at relapse, providing higher response rates, and importantly, increasing median overall survival.

Immunomodulation therapy with lenalidomide in follicular, transformed and diffuse large B cell lymphoma: current data on safety and efficacy

This review summarizes the results of current preclinical and clinical studies of lenalidomide, alone or in combination with the monoclonal antibody rituximab, as a therapeutic option for these three lymphoma types.

Treatment of Lymphoid and Myeloid Malignancies by Immunomodulatory Drugs.

  • O. Fuchs
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    Cardiovascular & hematological disorders drug targets
  • 2019
High level of full length CRBN mRNA in mononuclear cells of bone marrow and of peripheral blood seems to be necessary for successful therapy of del(5q) MDS with lenalidomide.

Lenalidomide in relapsed or refractory mantle cell lymphoma: overview and perspective

Lenalidomide’s nature of action and safety profile favor it over other agents studied in relapsed/refractory MCL, which seems to be responsible for its enhanced antitumor efficacy.

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The utility and potential role of these new agents in the treatment of non-Hodgkin lymphoma are reviewed with a specific focus on data that highlight how these agents may be incorporated into current standard treatment approaches.

The combination of thalidomide, cyclophosphamide and dexamethasone is potentially useful in highly resistant Hodgkin’s lymphoma

Two highly refractory patients with HL who successfully responded to a combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) achieving sustained complete remission that would support the running of a trial within this setting.



Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy.

Clinical activity of Thal against MM that is refractory to conventional therapy is demonstrated and mechanisms of anti-tumor activity of thalidomide and its potent analogs (immunomodulatory drugs [IMiDs]) are delineated.

The evolution of thalidomide and its IMiD derivatives as anticancer agents

A series of immunomodulatory drugs — created by chemical modification of thalidomide — have been developed to overcome the original devastating side effects, and their powerful anticancer properties mean that these drugs are now emerging from thalidmide's shadow as useful anticancer agents.

Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma.

In vitro and in vivo data support the hypothesis that Thal may mediate its anti-MM effect, at least in part, by modulating NK cell number and function.

Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo

The IMiDs were significantly more potent than thalidomide in vivo in suppressing tumor growth, evidenced by decreased tumor volume and prolonged survival, as well as mediating anti-angiogenic effects, as determined by decreased microvessel density.

Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects

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Lenalidomide (Revlimid), in combination with cyclophosphamide and dexamethasone (RCD), is an effective and tolerated regimen for myeloma patients

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Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications.

The mechanism of action of IMiDs against MM cells in vitro is delineated and form the basis for clinical trials of these agents, alone and coupled with conventional and other novel therapies, to improve outcome in MM.

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  • S. ScheyP. Fields A. Dalgleish
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
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This is the first report demonstrating in vivo T-cell costimulation by this class of compound, supporting a potential role for CC-4047 as an immunostimulatory adjuvant treatment.

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Thalidomide can induce marked and durable responses in some patients with multiple myeloma, including those who relapse after high-dose chemotherapy, and is active against advancedMyeloma.

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The recent return of thalidomide stems from the broad spectrum of its pharmacologic and immunologic effects.