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Plitidepsin: design, development, and potential place in therapy.

Sara Alonso-Álvarez1, Emilia Pardal2, Diego Sánchez-Nieto3

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Drug Design, Development and Therapy
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Plitidepsin shows limited antitumor activity as a single agent but enhanced efficacy with dexamethasone in multiple myeloma. Further research is needed to define its role and identify patient biomarkers.

Keywords:
aplidinlymphomamelanomamyelomaplitidepsin

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Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Plitidepsin, a cyclic depsipeptide from *Aplidium albicans*, is synthesized and marketed as Aplidin®.
  • Preclinical studies demonstrated antitumor activity, leading to extensive clinical trials over 17 years.

Purpose of the Study:

  • To critically analyze published studies on plitidepsin in hematological malignancies and solid tumors.
  • To discuss its current role and future perspectives in cancer treatment.
  • To review plitidepsin's design, pharmaceutical data, and mechanism of action.

Main Methods:

  • Review of published clinical trial data and preclinical studies on plitidepsin.
  • Analysis of plitidepsin's efficacy in various hematological malignancies and solid tumors.
  • Evaluation of plitidepsin in combination therapies, particularly with dexamethasone.

Main Results:

  • Single-agent plitidepsin demonstrated limited antitumor activity but a tolerable safety profile in noncutaneous peripheral T-cell lymphoma, melanoma, and multiple myeloma.
  • Plitidepsin's activity is enhanced with dexamethasone in relapsed/refractory multiple myeloma, with a Phase III trial ongoing.
  • Disappointing results were observed in other hematological malignancies and solid tumors.

Conclusions:

  • Plitidepsin shows promise in combination with dexamethasone for multiple myeloma, warranting further investigation.
  • Additional studies are required to define optimal combination strategies and identify predictive biomarkers for patient selection.
  • Further research into plitidepsin's mechanism of action is crucial for maximizing its therapeutic potential.