Belinostat, a novel pan-histone deacetylase inhibitor (HDACi), in relapsed or refractory peripheral T-cell lymphoma (R/R PTCL): Results from the BELIEF trial.

Lymphoma and Plasma Cell Disorders
Session Type and Session Title: 
Oral Abstract Session, Lymphoma
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 8507)
Owen A. O'Connor, Tamás Masszi, Kerry J. Savage, Lauren C. Pinter-Brown, Francine M. Foss, Leslie Popplewell, Amanda F. Cashen, Jeanette Doorduijn, Shanta Chawla, Poul Knoblauch, Pier Luigi Zinzani, Peter Brown, Georg Hess, Achiel Van Hoof, Steven M. Horwitz, Andrei R. Shustov; Center for Lymphoid Malignancies, Columbia University Medical Center, New York, NY; St. István and St. László Hospital, Budapest, Hungary; Department of Medical Oncology, British Columbia Cancer Agency Centre, Vancouver, BC, Canada; Geffen School of Medicine at UCLA, Los Angeles, CA; Yale Cancer Center, New Haven, CT; City of Hope, Duarte, CA; Washington University in St. Louis, St Louis, MO; Erasmus MC, Rotterdam, Netherlands; Spectrum Pharmaceuticals, IRVINE, CA; TopoTarget, Copenhagen, Denmark; Dipartimento di Ematologia e Scienze Oncologiche, Bologna, Italy; H:S Rigshospitalet, The Finsen Centre, KAT, Haematology Department 4241, Copenhagen, Denmark; Klinikum Johannes-Gutenberg -Universitaet, III. Medizinische Klinik und Poliklinik, Mainz, Germany; University Hospital St-Jan, Brugge, Belgium; Memorial Sloan-Kettering Cancer Center, New York, NY; University of Washington Medical Center, Seattle, WA

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Abstract Disclosures


Background: Therapies approved in US for R/R PTCL have overall response rates (ORR) of 25%-27%. The need for new therapies persists. BELIEF is a pivotal, single-arm study of belinostat in patients with R/R PTCL after failure of ≥1 prior systemic therapies. Methods: Entry criteria were measurable PTCL, platelets ≥ 50,000/µL, no prior HDACi therapy, and adequate organ function. PTCL was confirmed by central pathology review (CPRG). Belinostat 30 min IV infusion at 1000 mg/m2was administered on days 1–5 of a 3 week cycle until progression or unacceptable toxicity. Tumor response was assessed by Cheson 2007 criteria. The primary endpoint was ORR. Results: Patients with R/R PTCL (N=129, 53% male, median age 63 y) received belinostat a median of 2 cycles (range 1–33). The median number of prior therapies was 2 (1-8) including CHOP/CHOP-like (96%) and stem cell transplant (23%). The median administered dose intensity was 98%. One and two dose reductions of 25% occurred in 12% and 1% of patients, respectively, due to adverse events (AEs). For patients with CPRG confirmed PTCL (N=120), the ORR was 26% (n=31; 10% CR; 16% PR). The median time to response was 5.6 weeks (range 4.3-50.4). The median duration of response (DoR) was 8.3 months; longest DoR was 29.4 months. Seven patients remain on study in response. For the subgroup of patients with CPRG confirmed PTCL and baseline platelets ≥100,000/μL (N=100) ORR was 28% (CR 11%; PR 17%). The most frequent (≥ 5%) grade 3-4 treatment emergent AEs were thrombocytopenia (13%), neutropenia (13%), anemia (10%), dyspnea (6%), pneumonia (6%), and fatigue (5%). Patients with platelets <100K tolerated belinostat, with 98% dose intensity. Belinostat was well tolerated with a low incidence of myelosuppression. Discontinuations were due to PD (64%), death (11%), AEs (7%), patient request (8%), and other (4%). Conclusions: Belinostat demonstrated a 26%-28% ORR in BELIEF and was well tolerated with a favorable safety profile in patients with R/R PTCL including those with low platelets. The low incidence of myelosuppression observed warrants further investigation of belinostat combination therapy to develop new treatment paradigms for R/R PTCL. Clinical trial information: NCT00865969.