Sub-category : Multiple Myeloma
Category : Hematologic Malignancies—Plasma Cell Dyscrasia
Meeting : 2016 ASCO Annual Meeting
Abstract No : 8006
Author(s): Enrique M. Ocio, María-Victoria Mateos, Felipe Prosper, Jesus Martin, Albert Oriol Rocafiguera, Isidro Jarque, Rebeca Iglesias, Cristina Motlloo, Maria Sole, Paula Rodriguez-Otero, Sara Martinez, Eva Fernandez-Garcia, Jean-Marie Michot, Arturo Soto-Matos, Jose Rodriguez Diaz -Pavon, Vincent Ribrag, Jesus San Miguel; Hospital Universitario de Salamanca, Salamanca, Spain; University Hospital of Salamanca/IBSAL, Salamanca, Spain; Clinica Universitaria de Navarra, Pamplona, Spain; Hospital Virgen del Rocio, Sevilla, Spain; Hospital Universitario Germans Trias i Pujol, Barcelona, Spain; Hospital de la Fe, Valencia, Spain; MD Anderson Cancer Center, Madrid, Spain; PharmaMar, Madrid, Spain; Institut Gustave Roussy, Villejuif, France; Institut Goustave Roussy, Villejuif, France
Abstract Disclosures
Abstract:
Background : Despite recent progress, MM remains incurable, hence the need for agents with novel mechanisms of action. Marine-derived plitidepsin targets eEF1A2, a protein overexpressed in MM. Plitidepsin/dexamethasone showed activity in a phase I/II trial conducted in relapsed or refractory MM. Moreover, plitidepsin exhibited synergism with bortezomib and lenalidomide in human MM cell lines and tumor samples.
Methods : Relapsed and/or refractory MM patients were included if they had ECOG PS≤2 and CrCL>30 ml/min. Prior hematopoietic stem cell transplantation (HSCT) and previous treatment with bortezomib or other PIs and IMIDs was allowed. Primary objective: identification of the recommended dose (RD) for po dexamethasone (days 1,8,15,22)/s.c. bortezomib (days 1,4,8,11)/i.v. plitidepsin (days 1,15) administered every 4 weeks across 3 dose levels (DLs): DL1: 40 mg/1.0 mg/m2/4.0 mg/m2, DL2: 40mg/1.3mg/m2/4.0mg/m2 and DL3: 40mg/1.3mg/m2/5.0mg/m2.
Secondary objectives: evaluation of efficacy and overall safety.
Results : Twenty patients were enrolled. Median age was 65, median number of prior regimens was 3.5 (range, 1-10) and 9 patients had undergone HSCT. No dose-limiting toxicities (DLTs) were observed (n=20), therefore the RD was established at DL3. Hematological toxicity was manageable; grade 3-4 events included anemia (25%), neutropenia (25%) and thrombocytopenia (60%). Non-hematological toxicity was mainly mild. Out of 18 patients evaluable for efficacy, 15(83%) had received bortezomib and lenalidomide and 7/15 patients were refractory to lenalidomide. Overall response rate (ORR):56%, including 2 complete responses (11%), 4 very good partial responses (22%), 4 partial responses (22%) (one of them in a patient triple refractory to bortezomib, lenalidomide and pomalidomide) and 3 minimal responses (17%).
Clinical benefit : 72%, median PFS: 8.3 months, PFS 6 months: 58% and DOR 6 months: 90% (10 patients are still on-treatment).
Conclusions : the RD for dexamethasone/bortezomib/plitidepsin at the tested schedule was established at 40 mg/1.3 mg/m2/5 mg/m2. An ORR of 56% was observed, including ≥ VGPR:33%. The drug combination was well tolerated.
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La Hematóloga María Victoria Mateos forma parte de un equipo de Investigación que ha logrado estrechar el cerco al Mieloma con Aplidin ( un Nuevo Fármaco de origen marino ) .
Tenemos un mensaje esperanzador porque podemos considerar que Aplidina será un nuevo fármaco que se pueda incorporar al arsenal terapéutico de nuestros Pacientes con Mieloma.