Background
Phase 2, international, pivotal, single-arm, open-label study. 96 patients with stage IB–IVA refractory cutaneous T-cell lymphoma (CTCL) who had received ≥1 prior systemic therapy. Romidepsin is a bicyclic depsipeptide class I/II HDAC inhibitor. Enrolled patients had MF (76%) or SS (24%); median 2 prior therapies. Median age 60 years. This was the pivotal trial supporting FDA approval of romidepsin in CTCL.
Interventions and follow up
Regimen: Romidepsin 14 mg/m² IV on days 1, 8, and 15 of every 28-day cycle until progression or intolerance (relapsed/refractory CTCL)
Primary endpoint: Objective response rate (ORR) per SWAT tool
Median follow up: 13.4 months
Primary endpoint: Objective response rate (ORR) per SWAT tool
Median follow up: 13.4 months
Results
ORR: 34% (33/96 patients)
Complete response rate: 6% (6/96 patients)
Partial response rate: 28%
Median time to response: 2 months
Median duration of response: 15 months
Pruritus relief (≥3-point improvement): 43% (including non-responders)
Complete response rate: 6% (6/96 patients)
Partial response rate: 28%
Median time to response: 2 months
Median duration of response: 15 months
Pruritus relief (≥3-point improvement): 43% (including non-responders)
Adverse events
Gastrointestinal/constitutional: Nausea 56%, fatigue 55%, vomiting 34%, infections 33%
Hematologic/cardiac (grade ≥3): Thrombocytopenia 16%, neutropenia 23%, infections 19%. ECG T-wave and ST-segment changes observed but not clinically significant in the absence of hypokalemia/hypomagnesemia; electrolyte monitoring (potassium, magnesium) before each dose is required
Hematologic/cardiac (grade ≥3): Thrombocytopenia 16%, neutropenia 23%, infections 19%. ECG T-wave and ST-segment changes observed but not clinically significant in the absence of hypokalemia/hypomagnesemia; electrolyte monitoring (potassium, magnesium) before each dose is required
Conclusions
Romidepsin achieved a 34% ORR with 6% CR in refractory CTCL, with a clinically meaningful median response duration of 15 months. Pruritus relief was observed in 43% of patients including those without an objective response, indicating symptom benefit beyond tumor response. These results supported FDA approval of romidepsin as a second HDAC inhibitor option in CTCL.
Key Limitations
Single-arm, non-randomized phase 2 design without a comparator limits assessment of relative efficacy and durability. The composite SWAT-based response assessment complicates cross-trial comparison. ORR of 34% is modest and complete responses were infrequent (6%). Cardiac repolarization changes require electrolyte repletion and monitoring, restricting use in patients with cardiac comorbidity or QT-prolonging concomitant medications. No OS or randomized PFS data are available, and durability beyond the observed median response duration is uncertain.
Clinical Context
Romidepsin (Istodax) received FDA approval on November 5, 2009 for CTCL in patients who have received at least one prior systemic therapy, becoming the second HDAC inhibitor approved in this disease after vorinostat. It remains an option for relapsed/refractory MF/SS, particularly where pruritus control is desired. With the advent of brentuximab vedotin (CD30+ disease) and mogamulizumab (especially Sézary syndrome), HDAC inhibitors are now generally positioned among later-line choices. ESMO guidelines include romidepsin among systemic options for advanced/refractory CTCL.