Phase I study of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma
Por:
Mateos, MV, Prosper, F, Sanchez, JM, Ocio, EM, Oriol, A, Motllo, C, Michot, JM, Jarque, I, Iglesias, R, Sole, M, Martinez, S, Kahatt, C, Fudio, S, Corral, G, Zeaiter, A, Montilla, L and Ribrag, V
Publicada:
1 feb 2023
Ahead of Print:
1 sep 2022
Resumen:
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/m(2), BTZ 1.3 mg/m(2), 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.
Filiaciones:
Mateos, MV:
Hosp Univ Salamanca, Salamanca, Spain
Prosper, F:
Clin Univ Navarra, Pamplona, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain
Sanchez, JM:
Hosp Univ Virgen del Rocio, Seville, Spain
Ocio, EM:
Hosp Univ Salamanca, Salamanca, Spain
Univ Cantabria, Hosp Univ Marques de Valdecilla IDIVAL, Santander, Spain
:
Hosp Badalona Germans Trias & Pujol, Inst Catala Oncol, Badalona, Spain
:
Hosp Badalona Germans Trias & Pujol, Inst Catala Oncol, Badalona, Spain
Michot, JM:
Inst Gustave Roussy, Villejuif, France
Jarque, I:
Hosp Univ La Fe, Valencia, Spain
Iglesias, R:
MD Anderson Canc Ctr, Madrid, Spain
Sole, M:
Hosp Univ Virgen del Rocio, Seville, Spain
Martinez, S:
PharmaMar, Madrid, Spain
Kahatt, C:
PharmaMar, Madrid, Spain
Fudio, S:
PharmaMar, Madrid, Spain
Corral, G:
PharmaMar, Madrid, Spain
Zeaiter, A:
PharmaMar, Madrid, Spain
Montilla, L:
PharmaMar, Madrid, Spain
Ribrag, V:
Inst Gustave Roussy, Villejuif, France
Green Published, gold
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