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Phase I study of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma.
- Source :
-
Cancer Medicine . Feb2023, Vol. 12 Issue 4, p3999-4009. 11p. - Publication Year :
- 2023
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *DEPSIPEPTIDES
*MULTIPLE myeloma
*BORTEZOMIB
*DRUG interactions
*DEXAMETHASONE
Subjects
Details
- Language :
- English
- ISSN :
- 20457634
- Volume :
- 12
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Cancer Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 162145710
- Full Text :
- https://doi.org/10.1002/cam4.5250