Randomized Phase III Study (ADMYRE) of Plitidepsin in Combination with Dexamethasone vs. Dexamethasone Alone in Relapsed/Refractory Multiple Myeloma: Results for Patients Aged <75 Years

TL;DR

A clinical trial found that combining plitidepsin with dexamethasone improves survival and reduces disease progression in younger patients with advanced multiple myeloma.

Contribution

The study demonstrates improved efficacy of plitidepsin plus dexamethasone in patients under 75 with relapsed/refractory multiple myeloma.

Findings

Combining plitidepsin with dexamethasone reduced the risk of progression or death by 47.7% in patients under 75.

Median overall survival was 13.0 months for the combination group versus 8.1 months for dexamethasone alone.

The safety profile of the combination therapy was similar to the overall trial population.

Abstract

Age-related heterogeneity in efficacy has been found in several clinical trials evaluating new therapies in relapsed/refractory multiple myeloma (r/r MM). The aim of this pre-planned analysis from the ADMYRE trial was to evaluate the efficacy and safety of plitidepsin plus dexamethasone (DXM) compared to DXM alone in patients aged <75 years. The results show improved efficacy outcomes while also maintaining a similar safety profile compared to the overall ADMYRE population. These findings support the fact that this combination should be considered as another therapeutic option available for patients with extensively pretreated r/r MM.

Background: The phase III ADMYRE trial evaluated plitidepsin plus dexamethasone (DXM) versus DXM alone in patients with relapsed/refractory multiple myeloma (r/r MM). ADMYRE met its primary endpoint, showing a 35% reduction in the risk of progression or death. Methods: Results from a pre-planned subgroup of patients aged <75 years are shown here. This subgroup includes most of the patients evaluated in the ADMYRE study: 145/171 patients (84.8%) in the plitidepsin + DXM arm and 71/84 (84.5%) patients in the DXM alone arm. Results: Compared to the overall ADMYRE population, a higher reduction was found with plitidepsin plus DXM for the risk of progression or death in the primary endpoint: 47.7% vs. 35.0% (Hazard ratio [HR] = 0.523 vs. HR = 0.6509). Higher reduction in the risk of death was also found (28.9% vs. 20.3%; HR = 0.711 vs. HR = 0.797), with a clinically meaningful 5-month difference in median overall survival (13.0 months vs. 8.1 months; p = 0.0350). The safety profile of plitidepsin plus DXM in patients aged <75 years was similar to that observed in the overall population of patients treated in the ADMYRE study. The most common adverse events (all grades) related to the study treatment in patients < 75 years were fatigue (39.2% of patients), gastrointestinal (nausea, 39.2%; vomiting, 19.6%; diarrhea, 14.7%), and myalgia (14.0%). Conclusions: Larger differences in efficacy outcomes while maintaining a similar safety profile, together with a novel mechanism of action, suggest that this combination can be a valid option for patients with r/r MM aged <75 years.

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