Romidepsin for the treatment of relapsed/refractory peripheral T-cell lymphoma: pivotal study update demonstrates durable responses.

Abstract

BACKGROUND:

Romidepsin is a structurally unique, potent, bicyclic class 1 selective histone deacetylase inhibitor approved by the US Food and Drug Administration for the treatment of patients with cutaneous T-cell lymphoma who have received ≥ 1 prior systemic therapy and patients with peripheral T-cell lymphoma (PTCL) who have received ≥ 1 prior therapy. Approval for PTCL was based on results (n = 130; median follow-up, 13.4 months) from the pivotal study of romidepsin for the treatment of relapsed/refractory PTCL. The objective is to present updated data (median follow-up, 22.3 months) and to characterize patients who achieved long-term responses (≥ 12 months) to romidepsin.

METHODS:

Patients with PTCL who relapsed from or were refractory to ≥ 1 prior systemic therapy received romidepsin 14 mg/m2 as a 4-hour intravenous infusion on days 1, 8, and 15 every 28 days for up to 6 cycles; patients with response or stable disease could continue romidepsin beyond 6 cycles. The primary endpoint was rate of confirmed/unconfirmed complete response (CR/CRu) determined by an Independent Review Committee. Secondary endpoints included objective response rate (ORR) and duration of response (DOR). For patients who achieved CR/CRu, baseline characteristics by DOR (≥ 12 vs < 12 months) were examined.

RESULTS:

The ORR to romidepsin was 25%, including 15% with CR/CRu. The median DOR for all responders was 28 months (range, < 1-48+) and was not reached for those who achieved CR/CRu. Patients with lack of response or transient response to prior therapy achieved durable responses with romidepsin. Of the 19 patients who achieved CR/CRu, 10 had long-term (≥ 12 months) responses; none of the baseline characteristics examined-including heavy pretreatment, response to prior therapy, or advanced disease-precluded long-term responses to romidepsin. With a median progression-free survival of 29 months, patients who achieved CR/CRu for ≥ 12 months had significantly longer survival vs those with CR/CRu for < 12 months or < CR/CRu. Extended treatment and longer follow-up did not affect the reported safety profile of romidepsin.

CONCLUSIONS:

Treatment with romidepsin leads to highly durable responses in a subset of patients with relapsed/refractory PTCL, with responses ongoing as long as 48 months.

• Authors: Bertrand Coiffier, Barbara Pro, H Miles Prince, Francine Foss, Lubomir Sokol, Matthew Greenwood, Dolores Caballero, Franck Morschhauser, Martin Wilhelm, Lauren Pinter-Brown, Swaminathan Padmanabhan Iyer, Andrei Shustov, Tina Nielsen, Jean Nichols, Julie Wolfson, Barbara Balser, Steven Horwitz
• Journal: Journal of hematology & oncology (J Hematol Oncol) Vol. 7 Pg. 11 (Jan 23 2014) ISSN: 1756-8722 [Electronic] England
• PMID: 24456586 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Depsipeptides
• romidepsin

Topics

• Adult
• Aged
• Antibiotics, Antineoplastic (administration & dosage, adverse effects, therapeutic use)
• Cellulitis (chemically induced)
• Depsipeptides (administration & dosage, adverse effects, therapeutic use)
• Disease-Free Survival
• Drug Administration Schedule
• Drug Resistance, Neoplasm
• Female
• Humans
• Infusions, Intravenous
• Lymphoma, T-Cell, Peripheral (drug therapy, pathology)
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Prospective Studies
• Remission Induction
• Time Factors
• Treatment Outcome
• Venous Thrombosis (chemically induced)
• Vomiting (chemically induced)