In the study, 131 patients received 14 mg/m2 of ISTODAX 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.
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).
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.
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.
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.
ISTODAX® (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 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 ISTODAX is novel among the cyclic tetrapeptides. In vitro, ISTODAX causes the accumulation of acetylated histones, and induces cell cycle arrest and apoptosis of some cancer cell lines. For full prescribing information, visit www.ISTODAX.com.
Important U.S. Safety Information
ISTODAX® (romidepsin) for injection is indicated for treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy.
ISTODAX® (romidepsin) for injection is indicated for treatment of peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior therapy.
These indications are based on response rate. Clinical benefit such as improvement in overall survival has not been demonstrated.
Important Safety Information
WARNINGS AND PRECAUTIONS:
Peripheral T-Cell Lymphoma
Cutaneous T-Cell Lymphoma
USE IN SPECIFIC POPULATIONS:
Please see full Prescribing Information, including WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS.
ISTODAX® (romidepsin) for injection is indicated for treatment of peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior therapy. This indication is based on response rate. Clinical benefit such as improvement in overall survival has not been demonstrated.
Peripheral T-cell lymphoma is a term that encompasses a number of different malignancies of T-cell origin that account for about 10-15% of all cases of non-Hodgkin's lymphoma. PTCL can occur at any age from young adulthood to old age and is slightly more common in men than in women. It is a particularly aggressive form of lymphoma with a short median duration of life expectancy (approximately two years) from diagnosis.
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