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 · 4.71 Impact Factor
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- "Clinical features vary widely in this heterogeneous group of diseases, with varying symptoms and organ involvement. However, hematologic abnormalities are common in patients with PTCL and may be due to disease involvement in the bone marrow or prior myelosuppressive chemotherapy . Durable clinical responses in PTCL or advanced-stage CTCL are difficult to achieve [5,12,14]. "
ABSTRACT: Histone deacetylase inhibitor romidepsin has demonstrated durable clinical responses and tolerability in patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma (PTCL, CTCL). Selection of novel drug therapies for patients with relapsed/refractory aggressive lymphoma requires not only considerations regarding efficacy but also careful evaluation of toxicities as well as overall clinical benefit. The purpose of this analysis was to examine common adverse events (AEs) reported in pivotal trials of romidepsin in relapsed/refractory PTCL or CTCL and to more clearly define the overall AE profile in these populations. Patients with relapsed/refractory PTCL or CTCL were treated with romidepsin at 14 mg/m2 as a 4-hour intravenous infusion on days 1, 8, and 15 of 28-day cycles for up to 6 cycles; patients with at least stable disease could extend therapy until progressive disease or another withdrawal criterion was met. All enrolled patients who received ≥ 1 dose of romidepsin were included in the AE analyses. Overall, safety profiles of common AEs were similar, although patients with relapsed/refractory PTCL had more frequent hematologic toxicities and grade ≥ 3 infections. In both patient populations, the greatest incidence of grade ≥ 3 AEs and the majority of discontinuations due to AEs occurred during cycles 1–2. Early discontinuations were primarily related to infection, thrombocytopenia, or electrocardiogram abnormalities, confirming the need to closely monitor patients with poor bone marrow reserve or other comorbidities. Despite this, 28% of patients with relapsed/refractory PTCL and 36% of patients with relapsed/refractory CTCL continued on romidepsin treatment for ≥ 6 cycles. This study demonstrates that patients with relapsed/refractory PTCL or CTCL have similar AE profiles with romidepsin treatment, although patients with PTCL experienced more frequent and more severe hematologic toxicities and more frequent grade ≥ 3 infections. The greatest incidence of grade ≥ 3 AEs and the majority of discontinuations due to AEs occurred during treatment cycles 1–2. Extended dosing of romidepsin can be tolerated in responding patients. Trial registration NCT00426764, NCT0010643109/2014; 2(1):16. DOI:10.1186/2050-7771-2-16