Romidepsin (PTCL)

Background

Phase II, single-arm, multicenter pivotal study. 130 patients with relapsed/refractory peripheral T-cell lymphoma (PTCL, all subtypes) after ≥1 prior systemic therapy. Romidepsin is a class I selective HDAC inhibitor (cyclic depsipeptide). This study led to FDA accelerated approval of romidepsin for R/R PTCL.

Interventions and follow up

Regimen: Romidepsin 14 mg/m² IV on days 1, 8, 15 every 28d in R/R PTCL
Primary endpoint: Overall response rate (independent review committee)
Median follow-up: ~13.4 months (updated analysis ~34 months)

Results

ORR (primary): 25% (95% CI 18–34%)
CR/CRu rate: 15%
Median DoR: 17 months; not reached for patients achieving CR/CRu
Median PFS: 4 months
Durable responses: some CRs maintained beyond 34 months

Adverse events

Hematologic: Grade ≥3 thrombocytopenia 24%; grade ≥3 neutropenia 20%
Infectious: Grade ≥3 infections 19%
Gastrointestinal/constitutional: Nausea any grade 59%; fatigue common
Cardiac: ECG changes (T-wave, ST) common but not associated with clinical cardiac events on prospective monitoring

Conclusions

Romidepsin achieved a 25% ORR (15% CR/CRu) with durable responses (median DoR 17 months) in R/R PTCL, with some long-term remissions beyond 34 months, establishing it as an effective salvage option with a manageable toxicity profile distinct from pralatrexate (less mucositis).

Key Limitations

Single-arm Phase II with no randomized comparator; modest 25% ORR with low CR rate. Cumulative thrombocytopenia limits prolonged dosing. The subsequent Ro-CHOP randomized frontline trial failed to show PFS benefit of adding romidepsin to CHOP, tempering enthusiasm for combination strategies.

Clinical Context

Romidepsin received FDA accelerated approval (2011) for R/R PTCL after ≥1 prior therapy; the US PTCL indication was voluntarily withdrawn in 2021 after the confirmatory Ro-CHOP frontline trial was negative, though it remains a recognized salvage option. ESMO guidelines list HDAC inhibitors among options for R/R PTCL.

References