Randomized phase III study (ADMYRE) of plitidepsin in combination with dexamethasone vs. dexamethasone alone in patients with relapsed/refractory multiple myeloma
Journal
Annals of Hematology
Journal Volume
98
Journal Issue
9
Pages
2139-2150
Date Issued
2019
Author(s)
Spicka I.
Ocio E.M.
Oakervee H.E.
Greil R.
Banh R.H.
D'Rozario J.M.
Dimopoulos M.A.
Martínez S.
Extremera S.
Kahatt C.
Alfaro V.
Carella A.M.
Meuleman N.
Hájek R.
Symeonidis A.
Min C.-K.
Cannell P.
Ludwig H.
Sonneveld P.
Mateos M.V.
Abstract
The randomized phase III ADMYRE trial evaluated plitidepsin plus dexamethasone (DXM) versus DXM alone in patients with relapsed/refractory multiple myeloma after at least three but not more than six prior regimens, including at least bortezomib and lenalidomide or thalidomide. Patients were randomly assigned (2:1) to receive plitidepsin 5 mg/m2 on D1 and D15 plus DXM 40 mg on D1, D8, D15, and D22 (arm A, n = 171) or DXM 40 mg on D1, D8, D15, and D22 (arm B, n = 84) q4wk. The primary endpoint was progression-free survival (PFS). Median PFS without disease progression (PD) confirmation (IRC assessment) was 2.6 months (arm A) and 1.7 months (arm B) (HR = 0.650; p = 0.0054). Median PFS with PD confirmation (investigator's assessment) was 3.8 months (arm A) and 1.9 months (arm B) (HR = 0.611; p = 0.0040). Median overall survival (OS, intention-to-treat analysis) was 11.6 months (arm A) and 8.9 months (arm B) (HR = 0.797; p = 0.1261). OS improvement favoring arm A was found when discounting a crossover effect (37 patients crossed over from arm B to arm A) (two-stage method; HR = 0.622; p = 0.0015). The most common grade 3/4 treatment-related adverse events (% of patients arm A/arm B) were fatigue (10.8%/1.2%), myalgia (5.4%/0%), and nausea (3.6%/1.2%), being usually transient and reversible. The safety profile does not overlap with the toxicity observed with other agents used in multiple myeloma. In conclusion, efficacy data, the reassuring safety profile, and the novel mechanism of action of plitidepsin suggest that this combination can be an alternative option in patients with relapsed/refractory multiple myeloma after at least three prior therapy lines.
Subjects
Dexamethasone; Multiple myeloma; Plitidepsin; Refractory; Relapsed
SDGs
Other Subjects
dehydrodidemnin B; dexamethasone; antineoplastic agent; bortezomib; dehydrodidemnin B; depsipeptide; dexamethasone; lenalidomide; thalidomide; adult; aged; Article; cancer survival; clinical evaluation; controlled study; drug efficacy; drug safety; fatigue; female; human; intention to treat analysis; major clinical study; male; multiple myeloma; myalgia; nausea; overall survival; priority journal; prognosis; progression free survival; randomized controlled trial; risk factor; treatment duration; clinical trial; disease free survival; middle aged; mortality; multicenter study; multiple myeloma; phase 3 clinical trial; survival rate; very elderly; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Depsipeptides; Dexamethasone; Disease-Free Survival; Female; Humans; Lenalidomide; Male; Middle Aged; Multiple Myeloma; Survival Rate; Thalidomide
Publisher
Springer Verlag
Type
journal article