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

Journal of Hematology & Oncology

Steven Horwitz^1,10  Barbara Balser²  Julie Wolfson²  Jean Nichols^1,12  Tina Nielsen^1,13  Andrei Shustov⁹  Swaminathan Padmanabhan Iyer⁶  Lauren Pinter-Brown^1,14  Martin Wilhelm^1,15  Franck Morschhauser⁴  Dolores Caballero¹  Matthew Greenwood³  Lubomir Sokol^1,11  Francine Foss⁸  H Miles Prince⁷  Barbara Pro⁵  Bertrand Coiffier^1,16 

[1] Hospital Universitario de Salamanca, Salamanca, Spain;Veristat, LLC, Holliston, MA, USA;Royal North Shore Hospital, Sydney, Australia;Hôpital Claude Huriez, CHRU de Lille, Lille, France;Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA;The Methodist Hospital, Houston, TX, USA;Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Australia;Yale Cancer Center, New Haven, CT, USA;University of Washington, Seattle, WA, USA;Memorial Sloan-Kettering Cancer Center, New York, NY, USA;Moffitt Cancer Center, Tampa, FL, USA;JNichols LLC, Swampscott, MA, USA;Celgene Corporation, Summit, NJ, USA;UCLA Medical Center, Los Angeles, CA, USA;Klinikum Nürnberg Nord, Nürnberg, Germany;Hospices Civils de Lyon, Lyon, France

关键词: Duration of response;    Relapsed/refractory peripheral T-cell lymphoma;    Romidepsin;   

Others  :  802066
DOI  :  10.1186/1756-8722-7-11

 received in 2013-11-26, accepted in 2014-01-18,  发布年份 2014

【 摘 要 】

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.

Trial registration

NCT00426764

【 授权许可】

   
2014 Coiffier et al.; licensee BioMed Central Ltd.

【 图 表 】

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