Romidepsin for the treatment of relapsed/refractory peripheral T cell lymphoma: prolonged stable disease provides clinical benefits for patients in the pivotal trial

Abstract

BackgroundAchievement of durable responses in patients with relapsed/refractory peripheral T cell lymphoma (PTCL) is challenging with current therapies, and there are few data regarding the potential benefits of continuing treatment in patients with the best response of stable disease (SD). Histone deacetylase inhibitors are a novel class of drugs with activity in T cell malignancies. Romidepsin was approved by the US Food and Drug Administration for the treatment of relapsed/refractory PTCL based on a pivotal trial demonstrating an objective response rate of 25 % (33/130), including 15 % with confirmed/unconfirmed complete response and a median duration of response of 28 months. Our objective was to further study the clinical benefits of romidepsin in patients that had the best response of SD.MethodsPatients with PTCL relapsed/refractory to ≥1 prior therapy were treated with the approved dose of 14 mg/m2 romidepsin on days 1, 8, and 15 of six 28-day cycles; patients with SD or response after cycle 6 were allowed to continue on study until progression. By protocol amendment, patients treated for ≥12 cycles could receive maintenance dosing twice per cycle; after cycle 24, dosing could be further reduced to once per cycle in those who had received maintenance dosing for ≥6 months.ResultsOf the 32 patients (25 %) with the best response of SD, 22 had SD for ≥90 days (SD90; cycle 4 response assessment). The longest SD was >3 years in a patient who received maintenance dosing of 14 mg/m2 on days 1 and 15 beginning in cycle 13. Patients with the best response of SD90 or partial response achieved similar overall and progression-free survival. Prolonged dosing of romidepsin was well tolerated.ConclusionsWe concluded that patients who achieve SD may consider continuing treatment because the clinical benefits of romidepsin may extend beyond objective responses.Trial registrationNCT00426764

Peripheral T-cell lymphoma, not otherwise specified

“…The median PFS was 4 months for the entire cohort of patients, increasing to 18 months for patients in CR, and OS was 11.3 months. 57 As with other HDAC inhibitors, side effects associated with romidepsin are predominantly hematologic, including neutropenia, lymphopenia, thrombocytopenia, and anemia. Infections were commonly reported (55%), including upper respiratory tract and urinary infections, pneumonia, and sepsis, mostly in concomitance with reduced white blood cell counts.…”

Therapeutic applications of histone deacetylase inhibitors in sarcoma

“…For instance, tenovin-6 is a specific class III HDI that inhibits the activity of Sirtuin 1 and Sirtuin 2. Romidepsin (Istodax®, Gloucester Pharmaceuticals Inc.), also known as FK-228, FR901228, and depsipeptide, is a specific class I HDI that has been approved by the U.S. FDA for the clinical treatment of cutaneous T cell lymphoma 23 . There are also some novel HDIs, like PCI-48012 and PCI-34051, which specifically inhibit the activity of HDAC 8.…”

Targeting histone deacetylases in T-cell lymphoma

“…[46] Patients with best response of disease stabilization for 90 days (SD90; 23/130) had survival (median PFS and OS, 7 and 18 months, respectively) similar to those with PR. [46,48] A similarly designed trial from the National Cancer Institute (NCI) supported the approvals in CTCL (n ¼ 84; Tables 2 and 3) and PTCL (n ¼ 47; Tables 4 and 5). [36,49,50] The most common adverse events (AEs) in phase II studies of patients with CTCL and PTCL were gastrointestinal and asthenic conditions (Tables 3 and 5).…”