A phase 3 study assessed the efficacy and safety of plitidepsin (Aplidin) in combination with dexamethasone in patients with relapsed/refractory multiple myeloma.
Treatment with plitidepsin (Aplidin) in combination with dexamethasone significantly improved progression-free survival (PFS) in patients with heavily-treated multiple myeloma, according to results from the phase 3 ADMYRE study.
The findings, which were published in the Annals of Hematology, demonstrated the efficacy and safety of plitidepsin as a treatment option for patients with relapsed/refractory multiple myeloma after at least 3 prior therapy lines.
Plitidepsin, an experimental cancer therapy, works by binding to the eEF1A2 protein that is found on the surface of malignant myeloma cells to interfere with their growth and viability.
The study aimed to compare the safety and efficacy of plitidepsin in combination with dexamethasone versus dexamethasone monotherapy in a group of patients with relapsed or refractory multiple myeloma who had received between 3 and 6 prior therapies, including bortezomib (Velcade), and lenalidomide (Revlimid) or thalidomide.
A total of 255 patients were randomized to receive either the plitidepsin plus dexamethasone combination therapy (5 mg/m2 of plitidepsin on days 1 and 15 plus 40 mg of dexamethasone on days 1, 8, 15, and 22, every 4 weeks) or dexamethasone alone. The median number of prior therapies was 4 in both groups.
Overall, the results showed that adding plitidepsin to dexamethasone prolonged patients’ median PFS from 1.7 months to 2.6 months, which corresponded to a 35% reduction in the risk of disease progression or death.
Additionally, although plitidepsin led to a median overall survival (OS) of 11.6 months compared with 8.9 months for dexamethasone-treated patients, the difference did not reach statistical significance, according to the study.
However, after removing data from the patients who had switched from the control group to the active treatment group, the median OS remained 11.6 months and was estimated to be 6.4 months for the control group. This resulted in an approximately 38% decreased relative risk of death, the researchers noted.
The most common grade 3/4 treatment-related adverse events were fatigue, myalgia, and nausea.
“All recently introduced new myeloma drugs have mechanisms of activity not targeting eEF1A2,” the researchers wrote in the study. “This fact, together with the favorable safety profile and the lack of overlapping toxicities with commonly used agents, places plitidepsin as an alternative option for designing combinations or even for its administration after relapse in patients treated with immunotherapy.”
Spicka I, Ocio EM, Oakervee HE, et al. Randomized phase 3 study (ADMYRE) of pltidepsin in combination with dexamethasone vs. dexamethasone alone in patients with relapsed/refractory multiple myeloma. Annals of Hematology. 2019. https://link.springer.com/article/10.1007/s00277-019-03739-2#Sec1.