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A phase I/II trial of vorinostat (SAHA) in combination with rituximab‐CHOP in patients with newly diagnosed advanced stage diffuse large B‐cell lymphoma (DLBCL): SWOG S0806
Author(s) -
Persky Daniel O.,
Li Hongli,
Rimsza Lisa M.,
Barr Paul M.,
Popplewell Leslie L.,
Bane Charles L.,
Von Gehr Ann,
LeBlanc Michael,
Fisher Richard I.,
Smith Sonali M.,
Friedberg Jonathan W.
Publication year - 2018
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.25010
Subject(s) - vorinostat , medicine , diffuse large b cell lymphoma , rituximab , neutropenia , oncology , chop , febrile neutropenia , regimen , clinical endpoint , lymphoma , gastroenterology , histone deacetylase , chemotherapy , clinical trial , biology , histone , biochemistry , gene
Loss of major histocompatibility Class II expression (MHCII) in diffuse large B‐cell lymphoma (DLBCL) correlates with decreased survival. MHCII transcription is in part regulated by histone acetylation. We tested the hypothesis that combination of histone deacetylase inhibitor (HDACI) with standard chemotherapy would improve outcomes in DLBCL in part through increased MHCII expression. S0806 was a single arm phase I/II trial of vorinostat given at 400 mg po daily on days 1‐9 (subsequently amended to days 1‐5 due to toxicity), combined with R‐CHOP given on day 3 of a 21‐day cycle for 8 cycles, with primary phase II endpoint of 2‐year progression free survival (PFS). With 72 evaluable patients, at median follow up of 3 years, 2‐year PFS estimate was 73%, and OS estimate was 86%. Considering that the regimen fell short of predefined efficacy improvement and was associated with high rates of febrile neutropenia (38%) and sepsis (19%), it cannot be recommended for general use. Consistent with our hypothesis, patients with low MCHII expression on S0806 had numerically superior outcomes compared to those from trial S0433 which did not use an HDACI, but the difference was not statistically significant. Current studies are focused on finding biomarkers of response to HDACI.