Plitidepsin in combination with dexamethasone (ADMYRE trial) versus an external control arm of pomalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma

Plitidepsin (P) is a marine-derived anticancer compound isolated from the tunicate Aplidium albicans. P plus low-dose dexamethasone (LD-DXM) was evaluated versus LD-DXM alone in patients with relapsed/refractory multiple myeloma (r/r MM) in the randomized phase III ADMYRE trial. In absence of a randomized study with P + LD-DXM vs. POM + LD-DXM, a direct matched comparison between P + LD-DXM (ADMYRE data) and pomalidomide (POM) + LD-DXM as an External Control Arm (ECA) was conducted using individual patient-level data from several contemporary POM + LD-DXM trials with a similar design. A first analysis (ECA1) showed that P + LD-DXM was non-inferior to POM + LD-DXM in terms of median overall survival (OS): 11.8 vs. 13.9 months; HR = 1.009 (95%CI, 0.812–1.254; p = 0.9336). Safety profile showed a lower rate of grade ≥ 3 hematological treatment-related adverse events (TRAEs) (neutropenia 2.5% vs. 37.1%; thrombocytopenia 2.5% vs. 13.2%) and infections (8.1% vs. 18.7%) for P + LD-DXM, and a higher rate of grade ≥ 1 gastrointestinal TRAEs (52.8% vs. 27.4%), grade ≥ 3 blood creatine phosphokinase (14.3% vs. 0%) and grade ≥ 3 myalgia (5.6% vs. 0%). A second analysis (ECA2) compared POM + LD-DXM with the LD-DXM alone arm included in ADMYRE and showed a treatment effect in OS (HR = 0.762; 95%CI, 0.566–1.026) similar to that observed in ADMYRE (HR = 0.797, 95%CI, 0.596–1.067). Safety profile of POM + LD-DXM was associated to a higher rate of TRAEs, as expected for a combination. In conclusion, P + LD-DXM can be an alternative therapeutic option in r/r MM as this comparison shows that P + LD-DXM is non-inferior in OS to POM + LD-DXM with an advantageous safety profile in terms of hematological and infection events.