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 journalArticle

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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)1-11
Number of pages11
JournalLeukemia and Lymphoma
DOIs
StateAccepted/In press - Jan 12 2016

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Histocompatibility Antigens Class II
B-Cell Lymphoma
Tumor-Infiltrating Lymphocytes
T-Lymphocytes
Tumor Microenvironment
Lymphoma, Large B-Cell, Diffuse
Acetylation
Histones
Survival
belinostat
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

A phase II study of belinostat (PXD101) in relapsed and refractory aggressive B-cell lymphomas : SWOG S0520. / Puvvada, Soham D; Li, Hongli; Rimsza, Lisa M; Bernstein, Steven H.; Fisher, Richard I.; LeBlanc, Michael; Schmelz, Monika; Glinsmann-Gibson, Betty; Miller, Thomas P; Maddox, Anne Marie; Friedberg, Jonathan W.; Smith, Sonali M.; Persky, Daniel O.

In: Leukemia and Lymphoma, 12.01.2016, p. 1-11.

Research output: Contribution to journalArticle

Puvvada, Soham D ; Li, Hongli ; Rimsza, Lisa M ; Bernstein, Steven H. ; Fisher, Richard I. ; LeBlanc, Michael ; Schmelz, Monika ; Glinsmann-Gibson, Betty ; Miller, Thomas P ; Maddox, Anne Marie ; Friedberg, Jonathan W. ; Smith, Sonali M. ; Persky, Daniel O. / A phase II study of belinostat (PXD101) in relapsed and refractory aggressive B-cell lymphomas : SWOG S0520. In: Leukemia and Lymphoma. 2016 ; pp. 1-11.
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