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Romidepsin in peripheral and cutaneous T-cell lymphoma: mechanistic implications from clinical and correlative data.

ABSTRACT: Romidepsin is an epigenetic agent approved for the treatment of patients with cutaneous or peripheral T-cell lymphoma (CTCL and PTCL). Here we report data in all patients treated on the National Cancer Institute 1312 trial, demonstrating long-term disease control and the ability to retreat patients relapsing off-therapy. In all, 84 patients with CTCL and 47 with PTCL were enrolled. Responses occurred early, were clinically meaningful and of very long duration in some cases. Notably, patients with PTCL receiving romidepsin as third-line therapy or later had a comparable response rate (32%) of similar duration as the total population (38%). Eight patients had treatment breaks of 3.5 months to 10 years; in four of six patients, re-initiation of treatment led to clear benefit. Safety data show slightly greater haematological and constitutional toxicity in PTCL. cDNA microarray studies show unique individual gene expression profiles, minimal overlap between patients, and both induction and repression of gene expression that reversed within 24 h. These data argue against cell death occurring as a result of an epigenetics-mediated gene induction programme. Together this work supports the safety and activity of romidepsin in T-cell lymphoma, but suggests a complex mechanism of action.

SUBMITTER: Bates SE

PROVIDER: S-EPMC4675455 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Romidepsin in peripheral and cutaneous T-cell lymphoma: mechanistic implications from clinical and correlative data.

Bates Susan E SE Eisch Robin R Ling Alexander A Rosing Douglas D Turner Maria M Pittaluga Stefania S Prince H Miles HM Kirschbaum Mark H MH Allen Steven L SL Zain Jasmine J Geskin Larisa J LJ Joske David D Popplewell Leslie L Cowen Edward W EW Jaffe Elaine S ES Nichols Jean J Kennedy Sally S Steinberg Seth M SM Liewehr David J DJ Showe Louise C LC Steakley Caryn C Wright John J Fojo Tito T Litman Thomas T Piekarz Richard L RL

British journal of haematology 20150419 1

Romidepsin is an epigenetic agent approved for the treatment of patients with cutaneous or peripheral T-cell lymphoma (CTCL and PTCL). Here we report data in all patients treated on the National Cancer Institute 1312 trial, demonstrating long-term disease control and the ability to retreat patients relapsing off-therapy. In all, 84 patients with CTCL and 47 with PTCL were enrolled. Responses occurred early, were clinically meaningful and of very long duration in some cases. Notably, patients wit ...[more]

PMID: 25891346

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Project description:UnlabelledPeripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas associated with poor prognosis in most subtypes. Diagnosis of this rare disease by expert hematopathologists improves accuracy of subtyping, and referral to academic or specialty centers is recommended. Many patients, however, will receive treatment in the community, and knowledge of approved agents is key to optimizing therapeutic approaches for all patients. There is no current standard of care for patients with PTCL and no approved therapies for first-line treatment. Although many patients initially respond to induction chemotherapy, responses are often brief, and many patients relapse or become treatment refractory. For patients with relapsed or refractory PTCL, achievement of durable responses is challenging, and there are few treatment options. Romidepsin is a histone deacetylase inhibitor approved by the U.S. Food and Drug Administration for the treatment of patients with cutaneous T-cell lymphoma who have received one prior systemic therapy or more and patients with PTCL who have received one prior therapy or more. Approval of romidepsin for PTCL was based on a pivotal phase II study of patients with relapsed or refractory PTCL (n = 131) that demonstrated an objective response rate of 25% including 15% with complete response; responses lasted a median of >2 years. Long-term responses to romidepsin were achieved in patients regardless of baseline characteristics, including subtype, heavy pretreatment, response to prior therapy, or advanced disease. Common adverse events included hematologic abnormalities, gastrointestinal or asthenic conditions, and infections; romidepsin was not correlated with clinically meaningful QT prolongation or electrocardiogram abnormalities.Implications for practiceDue to the rarity, severity, and heterogeneous nature of peripheral T-cell lymphoma (PTCL), diagnosis by expert hematopathologists is preferred, and referral to specialty centers is recommended. Many patients, however, will receive treatment in the community, and community oncologists play a key role in the recognition and treatment of PTCL. Knowledge of approved agents is key for optimizing therapeutic approaches. This review provides an overview of PTCL and an in-depth examination of romidepsin, a histone deacetylase inhibitor approved for the treatment of relapsed or refractory PTCL, and highlights difficulties of diagnosis and optimization of treatment modalities for patients with PTCL.

Dataset Information

Romidepsin in peripheral and cutaneous T-cell lymphoma: mechanistic implications from clinical and correlative data.

Publications

Romidepsin in peripheral and cutaneous T-cell lymphoma: mechanistic implications from clinical and correlative data.

Similar Datasets

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