Plitidepsin (Aplidine) is a compound originally isolated from a marine tunicate (Aplidium Albicans) that demonstrated activity against Multiple Myeloma (MM) in preclinical studies conducted in our country by Dr. Enrique Ocio in collaboration with the Dana Farber Cancer Institute (Boston, MA).
Aplidine binds to a protein that is overexpressed in MM, eEF1A2 (eukaryotic translation elongation factor 1 alpha 2), inducing oxidative stress, activation of JNK and p38MAPK and, finally, apoptosis. These studies laid the foundations for their clinical development, with an initial study coordinated by the Spanish MM group, which showed responses in patients with this disease.
The Spanish leadership in the development of Aplidina is shown in the randomized phase III ADMYRE study reported in this publication. In this study, which has been carried out in 17 countries around the world, 255 patients with relapsed Multiple Myeloma who had received between 3 and 6 previous lines of treatment were randomized to receive Aplidine and Dexamethasone or Dexamethasone at low doses. The study was attended by Dr. Enrique Ocio, current head of the Hematology Service of the Marqués de Valdecilla University Hospital with a long research career in multiple myeloma. The study achieved its primary objective, since the median progression-free survival in patients receiving Aplidine doubled that observed with dexamethasone: 3.8 months versus 1.9 months (HR = 0.611; p = 0.0040. The toxicity profile was acceptable and similar of other similar drugs evaluated in a similar population of patients.
These data, in a drug with an alternative mechanism of action to those currently approved, support the use of Aplidine as a therapeutic alternative for patients with relapsed MM after at least three previous treatment lines.
