* Estudio llevado a cabo por Cientificos de : Oncotest GmbH, Freiburg, Germany y Pharma Mar S.A., Madrid, Spain .
* Abstract Number: 4472 .
* Presentation Title: Plitidepsin shows antitumor activity in patient-derived tumor xenografts and hematologic malignancies .
* Presentation Time: Tuesday, Apr 21, 2015, 1:00 PM - 5:00 PM .
Author Block: Armin Maier, Gerhard Kelter, Vincent Vuaroquaux, Pablo M. Avilés Marin, Carmen Cuevas, Carlos M. Galmarini, Heinz H. Fiebig. Oncotest GmbH, Freiburg, Germany; Pharma Mar S.A., Madrid, Spain
Abstract Body:
Plitidepsin is a new marine-derived anti-tumor agent, originally isolated from the tunicate Aplidium albicans that is now fully obtained by total chemical synthesis.
The compound is currently being evaluated in a pivotal phase III trial in patients with refractory/relapsed multiple myeloma. Previous in vitro studies in 26 hematological cell lines demonstrated that plitidepsin was more active in multiple myeloma and non-Hodgkin lymphoma compared to CML, AML and ALL derived cell lines as determined in a 4 day proliferation assay in suspension cultures. We have recently shown that plitidepsin interacts selectively with eEF1A2 (eukaryotic translation elongation factor 1 alpha 2) in tumor cells, which results in apoptotic cell death.
To identify target tumor types for future clinical studies, the inhibition of colony formation of plitidepsin was assessed in vitro in 116 established patient derived xenografts tumor models from 23 different tumor types, including solid tumors and hematological malignancies such as myeloma, leukemia and lymphoma.
The anti-tumor activity of plitidepsin varied depending on the concentration used, achieving a mean IC70 (inhibitory concentration of 70%) value of 3 nM (range between 0.03 nM and >1 µM), which can be also achieved in patients treated using the clinical recommended dose or less. 39 out of 116 tumors showed above average sensitivity (IC70 < 1nM) and IC70 values in these tumors were about 9-fold lower than the mean of all tumors as tested. Sensitive tumor types were seen among different tumor types, such as hematological malignancies, pleuramesothelioma, melanoma, small cell and non-small cell lung cancer (both adeno and large cell), as well as renal cancer. In conclusion plitidepsin showed a broad differential antitumor activity in vitro in hematological malignancies and in solid tumors. Bioinformatic analyses are currently underway to identify biomarkers and/or gene signatures that can predict sensitivity or resistance to plitidepsin for selecting patients being responsive to the drug.