Quick summary
Romidepsin (Istodax) is an FDA-approved bicyclic depsipeptide HDAC inhibitor originally isolated from Chromobacterium violaceum, used for cutaneous and peripheral T-cell lymphoma. It functions as a prodrug activated by intracellular glutathione reduction, selectively targeting class I HDACs.
Overview
Romidepsin (Istodax) is an FDA-approved bicyclic depsipeptide histone deacetylase (HDAC) inhibitor used for the treatment of cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL). Originally isolated from Chromobacterium violaceum, it was approved by the FDA in 2009 for CTCL and in 2011 for PTCL in patients who have received at least one prior therapy.
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.
Dosing protocols
| Purpose | Route | Dosage | Frequency | Notes |
|---|---|---|---|---|
| cutaneous or peripheral T-cell lymphoma | intravenous | 14–14 mg/m² | Days 1, 8, 15 of 28-day cycle | Infused over 4 hours. Ensure potassium ≥3.8 mEq/L and magnesium ≥0.85 mmol/L before each dose. Baseline and pre-dose ECG required. Dose-reduce for Grade 3+ toxicity. |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
FDA approval for CTCL in 2009 was based on two single-arm trials showing overall response rates of 34% and 35% in patients with refractory CTCL. The PTCL approval in 2011 was supported by a single-arm study demonstrating a 25% overall response rate in relapsed/refractory PTCL. Responses are often durable in responders. Cardiac monitoring (QT prolongation) is required prior to and during treatment. Ongoing studies are investigating romidepsin in combination with other lymphoma agents. Its unique bicyclic structure differentiates it from vorinostat and other HDAC inhibitors.[1][2][3][4]
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 since 2009 (CTCL) and 2011 (PTCL). Administered intravenously in an oncology setting. Not a controlled substance. Requires baseline and periodic ECG monitoring due to risk of QT prolongation. Electrolyte management recommended.
Sourcing & access
Prescription required
Romidepsin is an FDA-approved prescription medication available through licensed healthcare providers, telehealth platforms, and 503A/503B compounding pharmacies.
Frequently asked questions
Romidepsin (brand name Istodax) is an FDA-approved bicyclic depsipeptide histone deacetylase (HDAC) inhibitor. It received approval in 2009 for cutaneous T-cell lymphoma (CTCL) and in 2011 for peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior therapy. It is a natural product derived from Chromobacterium violaceum and belongs to the class of cyclic peptide oncology drugs.
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 carries a significant risk of QT interval prolongation, requiring baseline ECG and electrolyte monitoring. Serum potassium must be maintained at or above 3.8 mEq/L and magnesium at or above 0.85 mmol/L before each dose to reduce arrhythmia risk. Other common adverse effects include nausea, fatigue, cytopenias, and infections. It requires cardiac monitoring throughout treatment in a supervised oncology setting.
Pivotal trials in refractory CTCL demonstrated overall response rates of 34 to 35 percent, with responses often durable. In relapsed or refractory PTCL, the overall response rate was approximately 25 percent in a phase 2 trial. While response rates are modest compared to some oncology agents, responses in refractory T-cell lymphoma patients with few treatment options are considered clinically meaningful.
Research references
- Romidepsin (depsipeptide) for relapsed/refractory cutaneous T-cell lymphomaPubMed
- Romidepsin FDA approval and HDAC inhibitor mechanism in T-cell lymphomaPubMed
- HDAC inhibitors in peripheral T-cell lymphoma: class effects and romidepsin efficacyPubMed
- Romidepsin in combination regimens for T-cell lymphoma: safety and response ratesPubMed