Aplidin ( Plitidepsin ) ASCO18 - 4 de Junio . Aplidin en Combinación con DXM Demostró un Beneficio Clínicamente Significativo en Términos de Supervivencia Global en RRMM Altamente Pretratados . Una Enfermedad donde todavía se Necesitan Nuevas Alternativas Terapéuticas.

Overall Survival (OS) Results of Randomized Phase III study (ADMYRE trial) of Plitidepsin and Dexamethasone (DXM) vs. DXM Alone in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) : 

Evaluation of the Crossover Impact.

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Meeting : 2018 ASCO Annual Meeting

Author(s) : Javier Gomez, Sonia Extremera, Antonio Nieto; PharmaMar, Madrid, Spain.

Abstract:

Background: 

Plitidepsin is a synthetic cyclic depsipeptide isolated from the marine tunicate Aplidium albicans targeting the proto-oncogene eEF1A2, which is over-expressed in multiple myeloma cells. In ADMYRE trial, Plitidepsin plus dexamethasone (DXM) (Arm A) met the primary endpoint (progression-free survival) and showed a survival improvement versus DXM alone (Arm B) (ASH 2017).

Methods: 

RRMM patients with at least three but not more than six prior regimens, including at least bortezomib and lenalidomide/thalidomide, were randomized at 2:1 ratio to receive plitidepsin 5 mg/m2 D1 and 15 plus DXM 40 mg D1,8,15 and 22 (Arm A), or DXM 40 mg D1,8,15 and 22 (Arm B) every four weeks. The rank preserving structural failure time (RPSFT) and the two-stage methods were used to present overall survival (OS) results after mitigating the crossover effect.

Results:

Two-hundred fifty-five patients were enrolled: (Arm A: 171/Arm B: 84). Thirty-seven patients in Arm B (44%) switched to Arm A after progression. Intention-to-treat (ITT) analysis not discounting the crossover effect showed a 20.3% risk reduction in favor of Arm A (median OS: A 11.6 mo. B: 8.9 mo.; HR = 0.797; log-rank p = 0.1261). Risk reduction improved to 32.4% with the RPSFT method (median OS: A 11.6 mo. B: 7.2 mo.; HR = 0.676; log-rank p = 0.0103) and to 37.8% with the two-stage method (median OS: A 11.6 mo. B: 6.4 mo.; HR = 0.622; log-rank p = 0.0015). Although assumptions for RPFST and two-stage analyses were plausibly met, statistically significant risk reductions were still maintained when severe penalizations were applied, with median OS differences around four months.

Conclusions: 

Plitidepsin in combination with DXM demonstrated a clinically significant benefit in terms of overall survival in heavily pretreated RRMM, a disease where new therapeutic alternatives are still needed.

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