Posted: Wednesday, January 11, 2023
For patients with relapsed or refractory multiple myeloma who have failed to respond to standard treatment, combination therapy with the cyclic depsipeptide plitidepsin, dexamethasone, and bortezomib may be a promising therapeutic option, according to a phase I study published in Cancer Medicine. This combination treatment also had an acceptable safety profile with no pharmacokinetic drug-drug interactions, explained María Victoria Mateos, MD, PhD, of the Hospital Universitario de Salamanca, Spain, and colleagues.
From 2014 to 2018, a total of 36 patients with relapsed or refractory multiple myeloma were recruited for the study. All patients were treated with a standard 3 + 3 escalation-dose design. Initial doses included 4 mg/m2 of plitidepsin and 1 mg/m2 of bortezomib. Patients received plitidepsin on days 1 and 15 and received bortezomib on days 1, 4, 8, and 11. All patients were also given a standard 40-mg dose of dexamethasone on days 1, 8, 15, and 22.
The maximum dose evaluated by the study included 5.0 mg/m2 of plitidepsin, 1.3 mg/m2 of bortezomib, and 40.0 mg of dexamethasone. The study findings revealed an overall response rate of 22.2% and a clinical benefit rate of 77.8%. Two patients experienced dose-limiting toxicities that led to the cessation of treatment. They included grade 3 nausea and vomiting not responsive to antiemetic therapy and grade 3 diarrhea. Additional adverse effects reported by patients included thrombocytopenia (46%), anemia (33%), and neutropenia (17%). A total of 26% of patients also demonstrated elevated levels of alanine transaminase.
Disclosure: For full disclosures of the study authors, visit onlinelibrary.wiley.com.