Plitidepsin in combination with dexamethasone may be a feasible therapeutic alternative for patients with multiple myeloma who are refractory to multiple lines of treatment, according to research published in the Annals of Hematology.
A total of 250 patients with multiple myeloma who had received 3 to 6 prior lines of treatment were randomly assigned to receive either plitidepsin and dexamethasone (167 patients; arm A) or dexamethasone alone (83 patients; arm B). All patients received 40 mg dexamethasone once a week, and patients in arm A also received 5 mg/m2 intravenous plitidepsin on days 1 and 15 of a 4-week treatment cycle. Patients in arm B were allowed to cross over to arm A after 8 weeks.
An independent review committee found a 35.0% reduction in relative risk of progression or death with the combination treatment (P =.0062); median progression-free survival was 2.6 months in arm A and 1.7 months in arm B (P =.0054). An investigator’s assessment yielded a similar reduction in relative risk (38.9%; P =.0048).
Rate of mortality was 76.5%. Median overall survival was not significantly higher in arm A compared with arm B (11.6 vs 8.9 months; P =.1261); however, when crossover was accounted for in a 2-stage analysis, overall survival was found to be significantly higher in arm A (11.6 vs 6.4 months; P =.0015). In this analysis, there was a 37.8% decrease in relative risk of death in patients in arm A (P =.0016).
According to the independent review committee’s analysis, 13.8% of patients in arm A achieved partial response or better, compared with 1.7% of patients in arm B (P <.0080).
Treatment was discontinued in 15 patients receiving the combination therapy and 8 patients receiving dexamethasone due to adverse events. The most common adverse events of any grade in arm A were nausea (37.1%), fatigue (36.5%), and vomiting (16.8%), while the most common grade 3 or 4 adverse events were fatigue (10.8%), myalgia (5.4%), muscular weakness (3.6%), and nausea (3.6%). In arm B, nausea (10.8%), fatigue (8.4%), and insomnia (9.6%) were the most common adverse events.
The authors noted that because of its favorable safety profile and demonstrated efficacy, plitidepsin may be “an alternative option for designing combinations or even for its administration after relapse in patients treated with immunotherapy.”
Disclosures: Some authors have declared affiliations with the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
1. Spicka I, Ocio EM, Oakervee HE, et al. Randomized phase III study (ADMYRE) or plitidepsin in combination with dexamethasone vs. dexamethasone alone in patients with relapsed/refractory multiple myeloma [published online June 25, 2019]. Ann Hematol. doi:10.1007/s00277-019-03739-2