title: A phase II study of belinostat (PXD101) in relapsed and refractory aggressive B-cell lymphomas: SWOG S0520.
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.
authors.affiliation: a University of Arizona Cancer Center , Tucson , AZ , USA ;
authors.forename: Soham D
authors.initials: SD
authors.lastname: Puvvada
authors.affiliation: b SWOG Statistical Center , Seattle , WA , USA ;
authors.forename: Hongli
authors.initials: H
authors.lastname: Li
authors.affiliation: c Department of Pathology , University of Arizona , Tucson , AZ , USA ;
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rimsza
authors.affiliation: d Wilmot Cancer Center , University of Rochester , Rochester , NY , USA ;
authors.forename: Steven H
authors.initials: SH
authors.lastname: Bernstein
authors.affiliation: e Fox Chase Cancer Center - Temple Health , Philadelphia , PA , USA ;
authors.forename: Richard I
authors.initials: RI
authors.lastname: Fisher
authors.affiliation: b SWOG Statistical Center , Seattle , WA , USA ;
authors.forename: Michael
authors.initials: M
authors.lastname: LeBlanc
authors.affiliation: c Department of Pathology , University of Arizona , Tucson , AZ , USA ;
authors.forename: Monika
authors.initials: M
authors.lastname: Schmelz
authors.affiliation: c Department of Pathology , University of Arizona , Tucson , AZ , USA ;
authors.forename: Betty
authors.initials: B
authors.lastname: Glinsmann-Gibson
authors.affiliation: a University of Arizona Cancer Center , Tucson , AZ , USA ;
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Miller
authors.affiliation: f University of Arkansas for Medical Sciences , Little Rock , AK , USA ;
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Maddox
authors.affiliation: d Wilmot Cancer Center , University of Rochester , Rochester , NY , USA ;
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Friedberg
authors.affiliation: g Department of Medicine, University of Chicago , Chicago , IL , USA.
authors.forename: Sonali M
authors.initials: SM
authors.lastname: Smith
authors.affiliation: a University of Arizona Cancer Center , Tucson , AZ , USA ;
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Persky
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D019008:Drug Resistance, Neoplasm; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012008:Recurrence; D019233:Retreatment; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D006684:HLA-DR Antigens; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D013449:Sulfonamides; C487081:belinostat
keywords: CIITA; DLBCL; HDAC inhibition; MHC Class II expression; SWOG; non-Hodgkin lymphoma