Results From a Pivotal, Open-Label, Phase II Study of Romidepsin in Relapsed or Refractory Peripheral T-Cell Lymphoma After Prior Systemic Therapy

Hematology, Centre Hospitalier Lyon-Sud, 69310 Pierre-Benite, France.
Journal of Clinical Oncology (Impact Factor: 18.43). 02/2012; 30(6):631-6. DOI: 10.1200/JCO.2011.37.4223
Source: PubMed

ABSTRACT 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 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.
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%).
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.

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    • "Analog kwasu foliowego 111 29% 11% 10 miesięcy Romidepsin [32] Inhibitor deacetylazy histonowej 130 25% 15% 17 miesięcy Alisertib [33] "
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    • "However, a subsequent ad-hoc revision of the MVA with the inclusion of the use of RT as a variable was the most applicable method to evaluate the potential role of RT in this setting while accounting for other factors. Since 2009, four drugs have gained regulatory approval for the treatment of PTCL (O'Connor et al, 2011, 2013; Coiffier et al, 2012; Pro et al, 2012). Although two of these approvals "
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    • "Accordingly, vorinostat (Zolinza® or SAHA) and romidepsin (Istodax®) were approved by the FDA in 2006 and 2009, respectively, for the treatment of cutaneous T-cell lymphoma (CTCL) [6]. Also, in 2011, FDA approved romidepsin for the treatment of patients with peripheral T-cell lymphoma following at least one prior therapy [7]. Vorinostat and the HDAC class I specific inhibitor, MGCD01103, has been tested as a monotherapy for the treatment of relapsed and refractory DLBCL but with limited activity [8]. "
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