@article{10902/27874,
year = {2022},
month = {9},
url = {https://hdl.handle.net/10902/27874},
abstract = {Previous studies showed antitumor activity for plitidepsin plus dexamethasone (DXM) in relapsed/refractory multiple myeloma (r/r MM), and in vitro synergism with bortezomib (BTZ) or DXM against MM cells. This phase I trial evaluated plitidepsin (3-h intravenous infusion Day 1 and 15), BTZ (subcutaneous bolus Day 1, 4, 8, and 11), and DXM (orally Day 1, 8, 15, and 22), every 4 weeks in 36 r/r MM patients. Twenty-two patients were treated using a standard dose escalation design (10 at the recommended dose [RD] cohort), and 14 additional patients were treated to expand the RD cohort. No dose-limiting toxicities (DLTs) occurred during dose escalation. The highest dose level evaluated (plitidepsin 5.0 mg/m2 , BTZ 1.3 mg/m2 , DXM 40.0 mg) was the RD for phase II studies. Results shown herein are focused on this RD. Two patients had DLTs (grade 3 diarrhea, and grade 3 nausea/vomiting refractory to antiemetic therapy). Grade ? 3 hematological toxicity (thrombocytopenia 46%, anemia 33%, and neutropenia 17%) was manageable and did not result in treatment discontinuation. Transient and manageable grade 3 ALT increase (26%) was the most common biochemical abnormality. At the RD cohort, overall response rate was 22.2% (95%CI, 6.4%-47.6%), including one stringent complete response, one very good partial response, and two partial responses in r/r patients to BTZ and/or lenalidomide. The clinical benefit rate was 77.8% (95%CI, 52.4-93.6%). No major pharmacokinetic drug-drug interaction was found. In conclusion, the triple combination of plitidepsin, BTZ, and DXM showed an acceptable safety profile and had moderate activity in adult patients with r/r MM.},
organization = {FUNDING: The study was funded by Pharma Mar, S.A.
ACKNOWLEDGMENTS: The authors thank the patients, their families, and investigators teams for their participation in this phase I clinical trial.},
publisher = {John Wiley & Sons Ltd},
publisher = {Cancer Medicine. 2022;00:1-11},
title = {Phase I study of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma},
author = {Mateos, María Victoria and Prosper, Felipe and Sánchez, Jesús Martín and Ocio San Miguel, Enrique María and Oriol, Albert and Motlló, Cristina and Michot, Jean-Marie and Jarque, Isidro and Iglesias, Rebeca and Solé, María and Martínez, Sara and Kahatt, Carmen and Fudio, Salvador and Corral, Gema and Zeaiter, Ali and Montilla, Lola and Ribrag, Vincent},
}