Results From a Pivotal, Open-Label, Phase II Study of Romidepsin in Relapsed or Refractory Peripheral T-Cell Lymphoma After Prior Systemic Therapy
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.
- SourceAvailable from: Anna Czyż
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- "Analog kwasu foliowego 111 29% 11% 10 miesięcy Romidepsin  Inhibitor deacetylazy histonowej 130 25% 15% 17 miesięcy Alisertib  "
ABSTRACT: Peripheral T-cell lymphoma (PTCL) is relatively uncommon disorder representing only 8–15% of all non-Hodgkin lymphoma. The nodal types of PTCL, which include PTCL not otherwise specified, anaplastic large cell lymphomas (ALCLs), and angioimmunoblastic T cell lymphoma, are a heterogenous group of diseases that are challenging to treat. Although the outcome of patients with PTCL, with the exception of ALK-positive ALCL, is worse than that of patients with B cell lymphomas, they are treated similarly with the CHOP or CHOP-like regimens. The best treatment option for patients who responded to conventional chemotherapy remains undefined. Several prospective phase II studies support autologous hematopoietic stem cell transplantation as consolidation of first response for PTCL. Allogeneic transplant is usually reserved for relapsed disease. In addition, a variety of new drugs were registered in relapsed disease and are being studied in the upfront setting. This review summarizes the standard of care and new treatment options for the most common aggressive PTCL.Acta haematologica Polonica 03/2015; 46(2). DOI:10.1016/j.achaem.2015.02.016
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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 "
ABSTRACT: Current prognostic models for peripheral T-cell lymphoma (PTCL) have multiple limitations, and questions exist regarding applicability to current patients. We utilized the Surveillance Epidemiology and End Results (SEER)-18 database to evaluate factors affecting overall survival (OS) of PTCL in the modern era and identified 8802 patients between 2000–2010. Most subtypes of PTCL increased in incidence during the study period. In univariate analyses, age >55 years, black race, advanced stage, absence of extra-nodal disease, omission of radiation therapy (RT) and high-risk histology each predicted inferior OS (P < 0·0001). Multivariate analysis (MVA) demonstrated that hepatosplenic, enteropathy-associated and extra-nodal Natural Killer/T cell histologies, each had hazard ratios >1·5 (P ≤ 0·0001) for death. Further, age ≥55 years, black race and advanced stage maintained their significance in the MVA (P < 0·0001 each). Based on the significant factors, a prognostic model was constructed and subsequently validated in an independent cohort. The new model incorporated age, stage, histology and race, with an OS ranging from 9 months (highest risk group) to 120 months (lowest risk group). In summary, this is the largest study of PTCL patients in the modern era that provides risk stratification utilizing a new prognostic model that can be incorporated into future prospective clinical trials.British Journal of Haematology 11/2014; 168(5). DOI:10.1111/bjh.13202 · 4.96 Impact Factor
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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) . Also, in 2011, FDA approved romidepsin for the treatment of patients with peripheral T-cell lymphoma following at least one prior therapy . 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 . "
ABSTRACT: Epigenetic code modifications by histone deacetylase inhibitors (HDACis) have recently been proposed as potential new therapies for hematological malignancies. Diffuse large B-cell lymphoma (DLBCL) is the most common form of aggressive lymphoma. At present, standard first line treatment for DLBCL patients is the antracycline-based chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) combined with the monoclonal anti-CD20 antibody rituximab (R-CHOP). Since only 50-60% of patients reach a long-time cure by this treatment, there is an urgent need for novel treatment strategies to increase the response and long-term remission to initial R-CHOP therapy. In this study, we investigated the effect of the HDAC inhibitor valproic acid (VPA) on DLBCL cell lines. To elucidate the effects of VPA on chemo-sensitivity, we used a cell-line based model of CHOP-refractory DLBCL. All five DLBCL cell lines treated with VPA alone or in combination with CHOP showed decreased viability and proliferation. The VPA-induced sensitization of DLBCL cells to cytotoxic treatment resulted in increased number of apoptotic cell as judged by annexin V-positivity and the presence of cleaved caspase-3. In addition, pretreatment with VPA resulted in a significantly increased DNA-damage as compared to CHOP alone. In summary, HDAC inhibitors such as VPA, are promising therapeutic agents in combination with R-CHOP for patients with DLBCL.American Journal of Translational Research 01/2013; 5(2):170-83. · 3.23 Impact Factor