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

Soham D. Puvvada, Hongli Li, Lisa M. Rimsza, Steven H. Bernstein, Richard I. Fisher, Michael LeBlanc, Monika Schmelz, Betty Glinsmann-Gibson, Thomas P. Miller, Anne Marie Maddox, Jonathan W. Friedberg, Sonali M. Smith, Daniel O. Persky

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Recent advances in diffuse large B-cell lymphomas (DLBCL) have underscored the importance of tumor microenvironment in escaping host anti-tumor responses. One mechanism is loss of major histocompatibility Class II antigens (MHCII) associated with decreased tumor infiltrating T lymphocytes (TIL) and poor survival. Transcription of MHCII is controlled by CIITA which in turn is regulated by histone acetylation. In this study, we hypothesized that HDAC inhibition with belinostat increases MHCII, CIITA expression, TIL and improves patient outcomes. Primary objective was evaluation of toxicity and response. Twenty-two patients were enrolled for the study. Belinostat was well tolerated with mild toxicity. Two partial responses were observed at 5, 13 months after registration for an overall response rate (ORR) (95% CI) of 10.5% (1.3–33.1%), and three patients had stable disease for 4.7, 42.3+, and 68.4 + months with minimum 3-year follow-up. Included correlative studies support the hypothesis and serve as the basis for SWOG S0806 combining vorinostat with R-CHOP.

Original languageEnglish (US)
Pages (from-to)2359-2369
Number of pages11
JournalLeukemia and Lymphoma
Volume57
Issue number10
DOIs
StatePublished - Oct 2 2016

Keywords

  • CIITA
  • DLBCL
  • HDAC inhibition
  • MHC Class II expression
  • SWOG
  • non-Hodgkin lymphoma

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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