Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma

Abstract

Romidepsin (depsipeptide or FK228) is a histone deacetylase inhibitor, one of a new class of agents active in T-cell lymphoma. A phase 2 trial was conducted in cutaneous (CTCL) and peripheral (PTCL) T-cell lymphoma. Major and durable responses in CTCL supported the approval of romidepsin for CTCL. Forty-seven patients with PTCL of various subtypes including PTCL NOS, angioimmunoblastic, ALK-negative anaplastic large cell lymphoma, and enteropathy-associated T-cell lymphoma were enrolled. All patients had received prior therapy with a median of 3 previous treatments (range 1-11); 18 (38%) had undergone stem-cell transplant. All patients were evaluated for toxicity; 2 patients discovered to be ineligible were excluded from response assessment. Common toxicities were nausea, fatigue, and transient thrombocytopenia and granulocytopenia. Complete responses were observed in 8 and partial responses in 9 of 45 patients, for an overall response rate of 38% (95% confidence interval 24%-53%). The median duration of overall response was 8.9 months (range 2-74). Responses were observed in various subtypes, with 6 responses among the 18 patients with prior stem-cell transplant. The histone deacetylase inhibitor romidepsin has single agent clinical activity associated with durable responses in patients with relapsed PTCL.

Trial registration: ClinicalTrials.gov NCT00007345.

Figure 1

Patient responses. (A) Patient had recurrent PTCL, subtype not otherwise specified (NOS) after cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP); etoposide, methylprednisolone, cytarabine, and cisplatin (ESHAP); and autologous stem cell transplant. PET scan at 8 months showed no evidence of disease. The response was scored as CR and therapy was discontinued after 2 years with the patient remaining free of disease for another 53 months. (B) Patient with PTCL, subtype not otherwise specified (NOS), had prior CHOP and pralatrexate. Patient, who was declared a PR after 2 cycles of romidepsin and a CR afer 12 cycles of romidepsin, remained on study at 24 months as of data cutoff.

Figure 2

Time to progression. (A) Kaplan-Meier plot of time to progression is shown for descriptive purposes, separated by response category. The median time to progression was 13.0 months for CR+PR, 4.6 for SD and 1.4 for PD+NE. Note that TTP is biased in this analysis because PD or NE could occur at any time, while a categorical response necessitated a 2-cycle interval before disease reassessment occurred.