Thalidomide and lenalidomide: Mechanism-based potential drug combinations

@article{Vallet2008ThalidomideAL,
  title={Thalidomide and lenalidomide: Mechanism-based potential drug combinations},
  author={S. Vallet and A. Palumbo and N. Raje and M. Boccadoro and K. Anderson},
  journal={Leukemia \& Lymphoma},
  year={2008},
  volume={49},
  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… Expand
Treatment of Hematologic Neoplasms with New Immunomodulatory Drugs (IMiDs)
  • P. Wiernik
  • Medicine
  • Current treatment options in oncology
  • 2009
TLDR
The data suggest that thalidomide analogs will play a major role in the management of certain hematologic neoplasms in the near future. Expand
Future directions in immunomodulatory therapy
TLDR
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. Expand
Therapeutic effects of thalidomide in hematologic disorders: a review
TLDR
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. Expand
Novel Agents for Relapsed and/or Refractory Multiple Myeloma
TLDR
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. Expand
Immunomodulation therapy with lenalidomide in follicular, transformed and diffuse large B cell lymphoma: current data on safety and efficacy
TLDR
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. Expand
Treatment of Lymphoid and Myeloid Malignancies by Immunomodulatory Drugs.
  • O. Fuchs
  • Medicine
  • Cardiovascular & hematological disorders drug targets
  • 2019
TLDR
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. Expand
Lenalidomide in relapsed or refractory mantle cell lymphoma: overview and perspective
TLDR
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. Expand
Novel therapeutic agents for B-cell lymphoma: developing rational combinations.
TLDR
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. Expand
The combination of thalidomide, cyclophosphamide and dexamethasone is potentially useful in highly resistant Hodgkin’s lymphoma
TLDR
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. Expand
How lenalidomide is changing the treatment of patients with multiple myeloma.
TLDR
Results from pivotal phase III trials in this setting have demonstrated that Len/Dex extends overall survival compared with dexamethasone alone, and future studies will determine the efficacy of lenalidomide in novel combinations with potentially complimentary agents. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 86 REFERENCES
Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy.
TLDR
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. Expand
The evolution of thalidomide and its IMiD derivatives as anticancer agents
TLDR
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. Expand
Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma.
TLDR
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. Expand
Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo
TLDR
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. Expand
Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects
TLDR
This study assessed the anti-angiogenic activity of compounds from both IMiD™ and SelCID™ classes of analogues using a novel in vitro multicellular human assay system and the established rat aorta assay. Expand
Lenalidomide (Revlimid), in combination with cyclophosphamide and dexamethasone (RCD), is an effective and tolerated regimen for myeloma patients
TLDR
A retrospective analysis to assess the efficacy and toxicity profile when lenalidomide was used in combination with cyclophosphamide and dexamethasone for patients with relapsed refractory disease found the side effect profile of the combination was highly tolerable. Expand
Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications.
TLDR
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. Expand
Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma.
  • S. Schey, P. Fields, +5 authors A. Dalgleish
  • Medicine
  • Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2004
TLDR
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. Expand
Antitumor activity of thalidomide in refractory multiple myeloma.
TLDR
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. Expand
Thalidomide--a revival story.
TLDR
The recent return of thalidomide stems from the broad spectrum of its pharmacologic and immunologic effects. Expand
...
1
2
3
4
5
...