A Phase II trial of Belinostat (PXD101) in patients with relapsed or refractory peripheral or cutaneous T‐cell lymphoma

Abstract

SummaryBelinostat is a pan-histone deacetylase inhibitor with antitumour and anti-angiogenic properties. An open label, multicentre study was conducted in patients with peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL) who failed ≥1 prior systemic therapy and were treated with belinostat (1000 mg/m 2 intravenously 95 d of a 21-d cycle). The primary endpoint was objective response rate (ORR). Patients with PTCL (n = 24) had received a median of three prior systemic therapies (range 1-9) and 40% had stage IV disease. Patients with CTCL (n = 29) had received a median of one prior skin-directed therapy (range 0-4) and four prior systemic therapies (range 1-9); 55% had stage IV disease. The ORRs were 25% (PTCL) and 14% (CTCL). Treatment-related adverse events occurred in 77% of patients; nausea (43%), vomiting (21%), infusion site pain (13%) and dizziness (11%) had the highest incidence. Treatmentrelated serious adverse events were Grade 5 ventricular fibrillation; Grade 4 thrombocytopenia; Grade 3 peripheral oedema, apraxia, paralytic ileus and pneumonitis; and Grade 2 jugular vein thrombosis. Belinostat monotherapy was well tolerated and efficacious in patients with recurrent/refractory PTCL and CTCL. This trial was registered at www.clinicaltrials.gov as NCT00274651.

Peripheral T-cell lymphoma, not otherwise specified

“…An early phase 2 experience demonstrated an ORR of 25% in pretreated PTCL patients, along with a favorable toxicity profile. 64 The pivotal Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma (BELIEF) trial in patients with relapsed or refractory PTCL involved 129 patients, more than half of which were affected by PTCL-NOS. 65 Belinostat was IVadministered at the dose of 1000 mg/m 2 on days 1 through 5 every 3 weeks; treatment was continued until death or unacceptable toxicity.…”

The mTORC1 inhibitor everolimus has antitumor activity in vitro and produces tumor responses in patients with relapsed T-cell lymphoma

“…Much larger studies (111 to 130 patients) were required to validate the 25% ORR of romidepsin, 6 29% ORR for pralatrexate, 5 and 26% for belinostat. 8 However, to encourage large definitive trials, small pilots and in vitro data are required, especially when dealing with unusual types of lymphoma such as TCL.…”

“…[2][3][4] Progress has also been made in T-cell lymphoma (TCL) with the approval of the antifolate pralatrexate, 5 and the histone deacetylase inhibitors romidepsin 6,7 and belinostat. 8 These drugs are now being moved upfront in combination with chemotherapy. Despite these advances, the overall prognosis of TCL remains inferior to B-cell NHL with only 30% of patients cured with frontline therapy.…”

CCR 20th Anniversary Commentary: Expanding the Epigenetic Therapeutic Portfolio

“…Data from NCI1312 and the Gloucester Pharmaceuticals trials were submitted to the FDA, and romidepsin received approval for CTCL in 2009 and for PTCL in 2011. These observations, and those with vorinostat in CTCL, led to the evaluation of other HDAC inhibitors for patients with T-cell lymphoma, and the approval of belinostat for PTCL (16,19). These findings encouraged the development of HDAC inhibitors in other tumor types-panobinostat received FDA approval on February 23, 2015, for the treatment of multiple myeloma in combination with bortezomib (20).…”