Trial Watch: Lenalidomide-based immunochemotherapy

Michaela Semeraro, Erika Vacchelli, Alexander Eggermont, Jérôme Galon, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi

Research output: Contribution to journalReview articlepeer-review

48 Citations (Scopus)

Abstract

Lenalidomide is a synthetic derivative of thalidomide currently approved by the US Food and Drug Administration for use in patients affected by multiple myeloma (in combination with dexamethasone) and low or intermediate-1 risk myelodysplastic syndromes that harbor 5q cytogenetic abnormalities. For illustrative purposes, the mechanism of action of lenalidomide can be subdivided into a cancer cellintrinsic, a stromal, and an immunological component. Indeed, lenalidomide not only exerts direct cell cycle-arresting and proapoptotic effects on malignant cells, but also inhi their physical and functional interaction with the tumor microenvironment and mediates a robust, pleiotropic immunostimulatory activity. In particular, lenalidomide has been shown to stimulate the cytotoxic functions of T lymphocytes and natural killer cells, to limit the immunosuppressive impact of regulatory T cells, and to modulate the secretion of a wide range of cytokines, including tumor necrosis factor α, interferon γ as well as interleukin (IL)-6, IL-10, and IL-12. Throughout the last decade, the antineoplastic and immunostimulatory potential of lenalidomide has been investigated in patients affected by a wide variety of hematological and solid malignancies. Here, we discuss the results of these studies and review the status of clinical trials currently assessing the safety and efficacy of this potent immunomodulatory drug in oncological indications.

Original languageEnglish
Article numbere26494
JournalOncoImmunology
Volume2
Issue number11
DOIs
Publication statusPublished - 2013
Externally publishedYes

Keywords

  • CC-5013
  • Chronic lymphocytic leukemia
  • IMiDs
  • Pomalidomide
  • Regulatory T cells
  • TNFα

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