Romidepsin for the Treatment of Peripheral T-Cell Lymphoma

Abstract

Peripheral 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 forall patients.There is no current standard ofcare 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,andthere are few treatment options.Romidepsinis 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 5 131) 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, oradvanced 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. The Oncologist 2015;20:1084-1091 Implications for Practice: Due 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.

Phase I study of domatinostat (4SC‐202), a class I histone deacetylase inhibitor in patients with advanced hematological malignancies

“…Furthermore, significantly elevated expression levels of HDACs have been observed in a broad range of hematological malignancies, for example, elevated expression levels of HDACs 1, 2, and 6 in patients with cutaneous T‐cell lymphoma (CTCL) . Consequently, a variety of HDACi have been approved for hematological malignancies: As monotherapy, vorinostat by FDA for the treatment of cutaneous T‐cell lymphoma (CTCL), romidepsin by the FDA for the treatment of CTCL and peripheral T‐cell lymphoma (PTCL), chidamide in China by the CFDA for treatment of PTCL, belinostat by the FDA for the use against PTCL, and for combination treatment, panobinostat by the FDA and EMA for the treatment of multiple myeloma . Those and many others, broad‐spectrum HDACi as well as selective HDACi, are in clinical trials either as monotherapy or in combination in hematological and solid tumor indications, either as monotherapy or in combination …”

“…2,4,5 Furthermore, significantly elevated expression levels of HDACs have been observed in a broad range of hematological malignancies, for example, elevated expression levels of HDACs 1, 2, and 6 in patients with cutaneous T-cell lymphoma (CTCL). 6 Consequently, a variety of HDACi have been approved for hematological malignancies: As monotherapy, vorinostat by FDA for the treatment of cutaneous Tcell lymphoma (CTCL), 7 romidepsin by the FDA for the treatment of CTCL and peripheral T-cell lymphoma (PTCL), 8…”

Therapeutic Potential for Natural Product HDAC Inhibitors in Heart Failure

“…More recently, Romidepsin (FK-228) was approved to also treat T-cell lymphoma [29]. Valproic Acid, another HDACi is also currently available for human use; initially used to treat epilepsy, it has since become prominent for other neurological-related ailments [30].…”

Hepatoepigenetic Alterations in Viral and Nonviral-Induced Hepatocellular Carcinoma

“…Vorinostat (also known as SAHA) and romidepsin are two HDAC inhibitors (HDACIs) that were developed to treat a heterogeneous group of lymphoproliferative cutaneous T-cell lymphomas [161–163]. These HDACIs alter gene transcription by interfering with class 1 and II HDACs, leading to cell cycle arrest and apoptosis in a wide variety of transformed cells [13].…”