A phase II study of PXD101 (belinostat) in relapsed and refractory aggressive B-cell lymphomas (rel/ref ABCL): SWOG S0520.

e18536 Background: The mechanism of action of histone deacetylase inhibitors (HDACI) in lymphomas is unknown. Loss of major histocompatibility Class II antigens (MHC II) in diffuse large B-cell lymphomas (DLBCL) is associated with decreased tumor infiltrating T lymphocytes (TIL) and poor survival. Transcription of MHC II is controlled by CIITA, which is itself regulated by histone acetylation, We hypothesized that PXD101 (belinostat), an HDACI, would increase MHC II expression in tumor cells, enhance immunosurveillance and improve outcome. Methods: Theprimary objective was to evaluate response rate and toxicity of PXD101 in patients (pts) with rel/ref ABCL with up to 5 prior chemotherapy regimens. Secondary objectives were to estimate the 6-month progression-free survival (PFS) and to assess MHC II and TIL. In a two-stage design, if at least 1 response was observed in the first 20 pts, another 20 pts would be accrued. PXD101 was administered at 1000 mg/m2 IV days 1-5 of 21-day cycle for up to 2 years. Res...