Plitidepsin — Complete Research Guide (2026)

Last updated 2026-06-30

What is Plitidepsin?

Plitidepsin (brand name Aplidin) is a cyclic depsipeptide originally derived from the marine tunicate (sea squirt) Aplidium albicans and developed as an intravenous anticancer drug.

It is approved in Australia (TGA, 2018) in combination with dexamethasone for relapsed/refractory multiple myeloma but is NOT approved by the US FDA; the pivotal evidence is the randomized phase 3 ADMYRE trial.

It was also studied against COVID-19, but that work is preclinical/experimental and plitidepsin is not an approved treatment for any viral infection.

How does Plitidepsin work?

Plitidepsin binds the eukaryotic elongation factor 1A (eEF1A), disrupting protein translation and triggering oxidative stress and apoptosis in cancer cells.

The same eEF1A target underlies its investigated antiviral activity, since viruses depend on host translation machinery.

What does the research say about Plitidepsin?

• In the phase 3 ADMYRE trial, plitidepsin plus dexamethasone modestly improved progression-free survival versus dexamethasone alone in heavily pretreated relapsed/refractory multiple myeloma. ^[1]
• A subgroup analysis of ADMYRE suggested the progression-free survival benefit of plitidepsin plus dexamethasone was more pronounced in patients younger than 75 years. ^[2]
• Preclinical only: plitidepsin showed potent antiviral activity against SARS-CoV-2 in cell and animal models by targeting the host protein eEF1A, but this has not translated into an approved COVID-19 therapy. ^[5]

Clinical research & studies

The references below are the primary sources cited throughout this guide. Each links directly to PubMed or the regulator. Where evidence is preclinical (animal or in-vitro), that is stated rather than implied.

• [1] Randomized phase III study (ADMYRE) of plitidepsin in combination with dexamethasone vs. dexamethasone alone in patients with relapsed/refractory multiple myeloma — Spicka I et al., Annals of Hematology 2019. (Randomized phase 3 trial)
• [2] Randomized Phase III Study (ADMYRE) of Plitidepsin in Combination with Dexamethasone vs. Dexamethasone Alone in Relapsed/Refractory Multiple Myeloma: Results for Patients Aged Under 75 Years — Mateos MV et al., Cancers (Basel) 2025. (Phase 3 subgroup analysis)
• [3] Plitidepsin in combination with dexamethasone (ADMYRE trial) versus an external control arm of pomalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma — Ludwig H et al., Annals of Hematology 2026. (Indirect comparison / external-control analysis)
• [4] Evaluation of plitidepsin in patients with primary myelofibrosis and post polycythemia vera/essential thrombocythemia myelofibrosis: results of preclinical studies and a phase II clinical trial — Pardanani A et al., Blood Cancer Journal 2015. (Preclinical studies plus phase 2 trial)
• [5] Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A — White KM et al., Science 2021. (Preclinical (in vitro and animal))

Dosing context

In ADMYRE, plitidepsin was given as an intravenous infusion on a fixed schedule combined with dexamethasone, entirely within a controlled oncology setting.

Any dosing is determined and supervised by the treating physician; encyclopedic content does not provide administration instructions.

Side effects & safety profile

Reported toxicities include muscle toxicity (myalgia and creatine-kinase elevation), fatigue, nausea, bone-marrow suppression, and elevated liver transaminases.

Infusion-related reactions can occur, and it must be administered by oncology professionals with appropriate premedication and monitoring.

Because it is not FDA-approved, US access is limited to clinical trials or other regulated pathways; it is not a legitimate over-the-counter or research-use peptide.

Stacking & combinations

Its only established use is in combination with dexamethasone for multiple myeloma; other combinations remain investigational and should occur only within clinical trials.

Finding Plitidepsin vendors

User reviews

Frequently asked questions

References

1. [1] Randomized phase III study (ADMYRE) of plitidepsin in combination with dexamethasone vs. dexamethasone alone in patients with relapsed/refractory multiple myeloma — Spicka I et al., Annals of Hematology 2019. PMID: 31240472. View sourceStudy: Randomized phase 3 trialPlitidepsin plus dexamethasone improved progression-free survival over dexamethasone alone in relapsed/refractory myeloma.
2. [2] Randomized Phase III Study (ADMYRE) of Plitidepsin in Combination with Dexamethasone vs. Dexamethasone Alone in Relapsed/Refractory Multiple Myeloma: Results for Patients Aged Under 75 Years — Mateos MV et al., Cancers (Basel) 2025. PMID: 41228275. View sourceStudy: Phase 3 subgroup analysisBenefit of plitidepsin plus dexamethasone appeared more pronounced in patients younger than 75.
3. [3] Plitidepsin in combination with dexamethasone (ADMYRE trial) versus an external control arm of pomalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma — Ludwig H et al., Annals of Hematology 2026. PMID: 41545603. View sourceStudy: Indirect comparison / external-control analysisCompared ADMYRE plitidepsin outcomes against an external pomalidomide-dexamethasone control arm.
4. [4] Evaluation of plitidepsin in patients with primary myelofibrosis and post polycythemia vera/essential thrombocythemia myelofibrosis: results of preclinical studies and a phase II clinical trial — Pardanani A et al., Blood Cancer Journal 2015. PMID: 25768401. View sourceStudy: Preclinical studies plus phase 2 trialPlitidepsin showed limited clinical activity in myelofibrosis despite preclinical rationale.
5. [5] Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A — White KM et al., Science 2021. PMID: 33495306. View sourceStudy: Preclinical (in vitro and animal)Plitidepsin inhibited SARS-CoV-2 in cell and mouse models via the host factor eEF1A.