Data from a sub-analysis of a Phase II, multicenter, international, open-label study of romidepsin (Istodax?, Celgene Corporation) in refractory or relapsed peripheral T-Cell lymphoma (PTCL) following prior systemic therapy, showed that 46% of patients experienced disease control for at least 90 days. Similar response rates demonstrated across most common subtypes of PTCL. The study results were presented by Professor Bertrand Coiffier, Hospices Civils de Lyon and Universit? Lyon 1, Lyon, France at the 53rd American Society of Hematology Annual Meeting (ASH) in San Diego, CA.

In the study, 131 patients received 14 mg/m2 of romidepsin as a 4-hour intravenous infusion on days 1, 8 and 15 of a 28-day cycle for up to six cycles. Treatment could be extended beyond six cycles in patients who achieved response or had stable disease. Efficacy assessments were made by an Independent Review Committee (IRC) and consisted of an initial radiographic review of images using computed tomography (CT) or magnetic resonance imaging (MRI) followed by an overall clinical assessment based on radiologic evaluations, photographs, and relevant clinical parameters.

Investigational drug
Romidepsin is a member of a class of cancer drugs known as histone deacetylase (HDAC) inhibitors. HDACs catalyze the removal of acetyl groups from acetylated lysine residues in histones, resulting in the modulation of gene expression. HDACs also deacetylate non-histone proteins, such as transcription factors. HDAC inhibitors such as romidepsin can be divided into four main classes: cyclic tetrapeptides (I), short-chain fatty acids (II), hydroxamic acids (III), and benzamides (IV). The cyclic peptide structure of romidepsin is novel among the cyclic tetrapeptides. In vitro, romidepsin causes the accumulation of acetylated histones, and induces cell cycle arrest and apoptosis of some cancer cell lines.

Trial results
The sub-analysis assessed the efficacy and safety of romidepsin in the most common subtypes of PTCL: PTCL not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic lymphoma kinase-1?negative anaplastic large cell lymphoma (ALK-1?negative ALCL). Of the 130 patients with histologically-confirmed PTCL by central review, 117 had a more common subtype, including PTCL-NOS (n=69), AITL (n=27) and ALK-1?negative ALCL (n=21).

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Overall response rates (ORR) consisting of confirmed and unconfirmed complete responses and partial responses (CR+CRu+ PR) were similar across the three most common subtypes: 29% (20/69) of patients with PTCL-NOS, 30% (8/27) of patients with AITL and 24% (5/21) of patients with ALK-1?negative ALCL. Similar rates of complete response (CR/CRu), the primary study endpoint, were also observed across the three most common subtypes: 14% (10/69), 19% (5/27) and 19% (4/21) for PTCL-NOS, AITL and ALK-1-negative ALCL, respectively. Disease control (defined as ORR + stable disease [SD] of 90 days or longer) was noted in 46% (54/117) of patients with the most common PTCL subtypes with 49% (34/69), 44% (12/27), and 38% (8/21) for PTCL-NOS, AITL, and ALK-1-negative ALCL, respectively.

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Median follow-up
With a median follow-up of 21 months, the median duration of response (DOR) for all responders (CR+CRu+PR) was 17 months. For patients with PTCL-NOS and ALK-1?negative ALCL the median DOR was 17 months and 12 months, respectively. Median DOR was not yet evaluable for patients with AITL, who had the longest DOR ongoing at 34 months.

Adverse events
The most common (? 10%) grade 3 or higher adverse events among patients with PTCL-NOS, AITL and ALK-1-negative ALCL subtypes included: thrombocytopenia (22% [15/69], 30% [8/27], 29% [6/21]), neutropenia (17% [12/69], 22% [6/27], 14% [3/21]), infections (13% [9/69], 22% [6/27], 14% [3/21]) and anemia (6% [4/69], 15% [4/27], 10% [2/21]). Romidepsin was discontinued due to infection in 1 patient with PTCL-NOS and 3 patients with ALK-1?negative ALCL.

For more information:
For full prescribing information of romidepsin.

Clinical trials
– A Study of Escalating Doses of Romidepsin in Association With CHOP in the Treatment of Peripheral T-Cell Lymphomas (Ro-CHOP)(NCT01280526)
– A Trial of Romidepsin for Progressive or Relapsed Peripheral T-cell Lymphoma (NCT00426764)
– A Rollover Study for Subjects Who Participated in Other Romidepsin Protocols (NCT01353664).

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