Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy.

Abstract

PURPOSE:

Romidepsin is a structurally unique, potent class 1 selective histone deacetylase inhibitor. The primary objective of this international, pivotal, single-arm, phase II trial was to confirm the efficacy of romidepsin in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).

PATIENTS AND METHODS:

Patients who were refractory to at least one prior systemic therapy or for whom at least one prior systemic therapy failed received romidepsin at 14 mg/m(2) as a 4-hour intravenous infusion on days 1, 8, and 15 every 28 days. The primary end point was the rate of complete response/unconfirmed complete response (CR/CRu) as assessed by an independent review committee.

RESULTS:

Of the 131 patients enrolled, 130 had histologically confirmed PTCL by central review. The median number of prior systemic therapies was two (range, one to eight). The objective response rate was 25% (33 of 130), including 15% (19 of 130) with CR/CRu. Patient characteristics, prior stem-cell transplantation, number or type of prior therapies, or response to last prior therapy did not have an impact on response rate. The median duration of response was 17 months, with the longest response ongoing at 34+ months. Of the 19 patients who achieved CR/CRu, 17 (89%) had not experienced disease progression at a median follow-up of 13.4 months. The most common grade ≥ 3 adverse events were thrombocytopenia (24%), neutropenia (20%), and infections (all types, 19%).

CONCLUSION:

Single-agent romidepsin induced complete and durable responses with manageable toxicity in patients with relapsed or refractory PTCL across all major PTCL subtypes, regardless of the number or type of prior therapies. Results led to US Food and Drug Administration approval of romidepsin in this indication.

• Authors: Bertrand Coiffier, Barbara Pro, H Miles Prince, Francine Foss, Lubomir Sokol, Matthew Greenwood, Dolores Caballero, Peter Borchmann, Franck Morschhauser, Martin Wilhelm, Lauren Pinter-Brown, Swaminathan Padmanabhan, Andrei Shustov, Jean Nichols, Susan Carroll, John Balser, Barbara Balser, Steven Horwitz
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 30 Issue 6 Pg. 631-6 (Feb 20 2012) ISSN: 1527-7755 [Electronic] United States
• PMID: 22271479 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Depsipeptides
• romidepsin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibiotics, Antineoplastic (therapeutic use)
• Depsipeptides (adverse effects, therapeutic use)
• Diarrhea (chemically induced)
• Disease-Free Survival
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Humans
• Kaplan-Meier Estimate
• Lymphoma, T-Cell, Peripheral (drug therapy)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Pneumonia (chemically induced)
• Treatment Outcome
• Vascular Diseases (chemically induced)
• Vomiting (chemically induced)
• Young Adult