Cite this answer
Romidepsin: quick citable summary
Romidepsin is listed by PeptaHub as a other peptide with a prescription legal-status classification. The page summarizes mechanism, research context, common routes, safety notes, and references for writers and AI answer engines.
PeptaHub. “Romidepsin: Mechanism, Research Context, Safety.” peptahub.com, 2026. https://peptahub.com/peptides/romidepsin. Licensed CC BY 4.0.
License: Creative Commons Attribution 4.0 International. Link back to https://peptahub.com/peptides/romidepsin.
What is Romidepsin?
Romidepsin (Istodax) is an FDA-approved bicyclic depsipeptide HDAC inhibitor and prescription chemotherapy for cutaneous T-cell lymphoma after at least one prior systemic therapy. Its peripheral T-cell lymphoma indication was withdrawn in 2022 after the confirmatory trial failed.
Overview
Romidepsin (Istodax) is an FDA-approved bicyclic depsipeptide histone deacetylase (HDAC) inhibitor indicated for cutaneous T-cell lymphoma (CTCL) in adults who have received at least one prior systemic therapy. Originally isolated from Chromobacterium violaceum, it was approved for CTCL in 2009. It also held an accelerated approval for peripheral T-cell lymphoma (PTCL) granted in 2011, but that indication was voluntarily withdrawn after the confirmatory Ro-CHOP Phase 3 trial failed; FDA withdrawal of the PTCL approval took effect May 9, 2022. CTCL is now the only approved indication.
Mechanism of action
Romidepsin is a natural product bicyclic depsipeptide that functions as a prodrug. Upon cellular uptake, its disulfide bridge is reduced by intracellular glutathione, releasing the reduced thiol form, which then chelates the zinc ion in the active sites of class I HDAC enzymes (primarily HDAC1 and HDAC2). Inhibition of HDACs prevents the removal of acetyl groups from lysine residues on histone tails, resulting in hyperacetylation of histones, chromatin relaxation, and altered transcription of genes involved in cell cycle control and apoptosis. This leads to upregulation of p21 (cell cycle arrest), activation of intrinsic and extrinsic apoptotic pathways, and downregulation of anti-apoptotic proteins in T-cell lymphoma cells. Because malignant T cells show heightened dependence on HDAC1/2 activity, romidepsin exhibits selective cytotoxicity in this context.
Reported study ranges
| Purpose | Route | Reported range | Frequency | Notes |
|---|---|---|---|---|
| cutaneous T-cell lymphoma (only approved indication) | intravenous | 14–14 mg/m² | Days 1, 8, 15 of 28-day cycle | Infused over 4 hours; cycles repeat every 28 days while the patient benefits and tolerates treatment. The label directs confirming that potassium and magnesium are within the normal range before administration, and says to consider ECG monitoring in patients with congenital long QT syndrome, significant cardiovascular disease, or on QT-prolonging drugs. Reduce to 7 mg/m² in moderate hepatic impairment and 5 mg/m² in severe hepatic impairment. Dose-reduce for Grade 3+ toxicity. |
Reported ranges are for research context only. Consult a qualified healthcare professional before using any peptide.
Convert Romidepsin research-range units
Need to convert mg to mcg, dose volume, or U-100 syringe units? Use the peptide dose unit converter for educational calculation support.
Research summary
FDA approval for CTCL in 2009 was based on two single-arm trials. Whittaker et al. (J Clin Oncol 2010, n=96) reported an overall response rate of 34%, and Piekarz et al. (J Clin Oncol 2009, n=71) reported 34%. The 2011 PTCL accelerated approval rested on Coiffier et al. (J Clin Oncol 2012, n=131), a single-arm study with a 25% overall response rate on the surrogate endpoint of response. The required confirmatory trial, Ro-CHOP (Bachy et al., J Clin Oncol 2022), compared romidepsin plus CHOP against CHOP in previously untreated PTCL and did not meet its primary progression-free-survival endpoint. Celgene voluntarily withdrew the PTCL indication in 2021 and FDA withdrew approval effective May 9, 2022. Romidepsin remains approved for CTCL only.[1][2][3][4][5]
Evidence grading
Each claimed benefit is graded by the strength of available evidence. Grades reflect study quality, not effect size.
Strong = multiple RCTs · Moderate = limited trials or observational · Preliminary = animal or in vitro only · Insufficient = anecdotal or no published data
Side effects
Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.
Common stacks
Peptides commonly paired with Romidepsin for synergistic effects.
Legal status
FDA-approved for cutaneous T-cell lymphoma in adults who have received at least one prior systemic therapy. This is the only current indication: the peripheral T-cell lymphoma accelerated approval was withdrawn effective May 9, 2022 after its confirmatory trial failed. Prescription chemotherapy administered intravenously in an oncology setting; not a research peptide and not a controlled substance. The label lists no contraindications and carries no boxed warning, but warns on myelosuppression, infections, electrocardiographic changes, tumor lysis syndrome and embryo-fetal toxicity.
Sourcing & access
Prescription required
Romidepsin is an FDA-approved prescription medication available through licensed healthcare providers, pharmacies, and label-appropriate access programs; compounded access depends on current FDA shortage status and compounding rules.
Frequently asked questions
Romidepsin (brand name Istodax) is an FDA-approved bicyclic depsipeptide histone deacetylase (HDAC) inhibitor and a prescription chemotherapy agent. It received approval in 2009 for cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy, which is its only current indication. It also received accelerated approval for peripheral T-cell lymphoma (PTCL) in 2011, but that indication was withdrawn in 2022 after the confirmatory trial failed. It is a natural product derived from Chromobacterium violaceum.
Romidepsin is a prodrug activated intracellularly: glutathione reduces its disulfide bond to release a free thiol that chelates the zinc ion in the catalytic domain of class I HDACs (HDAC1 and HDAC2). HDAC inhibition prevents histone deacetylation, leading to hyperacetylation and chromatin relaxation. This reactivates silenced tumor suppressor genes and triggers cell cycle arrest and apoptosis selectively in malignant T cells.
Romidepsin is cytotoxic chemotherapy given under oncology supervision, not a wellness peptide. The label carries no boxed warning and lists no contraindications, but it warns on myelosuppression, serious and fatal infections, electrocardiographic changes, tumor lysis syndrome and embryo-fetal toxicity. It can cause fetal harm, and effective contraception is required during treatment and for one month after the last dose. The label directs confirming that potassium and magnesium are in the normal range before each dose, and advises considering ECG monitoring in patients with congenital long QT syndrome, significant cardiovascular disease, or those taking QT-prolonging medications. Dose reductions apply in moderate and severe hepatic impairment.
In refractory CTCL, the two single-arm pivotal trials each reported an overall response rate of about 34 percent. These were uncontrolled studies, so they show tumour response rather than a survival benefit. In relapsed or refractory PTCL the response rate was about 25 percent, but that indication has since been withdrawn: the required confirmatory Phase 3 trial (Ro-CHOP) missed its primary endpoint, and FDA withdrew the PTCL approval in 2022.
Research references
- Final results from a multicenter, international, pivotal study of romidepsin in refractory cutaneous T-cell lymphomaPubMed
- Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphomaPubMed
- Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapyPubMed
- Romidepsin Plus CHOP Versus CHOP in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Results of the Ro-CHOP Phase III Study (Conducted by LYSA)PubMed
- Romidepsin (Istodax, NSC 630176, FR901228, FK228, depsipeptide): a natural product recently approved for cutaneous T-cell lymphomaReview