The Systemic Effects of Vorinostat in Patients (Pts) with Cutaneous T-Cell Lymphoma (CTCL): Post-Hoc Analyses in Pts with High Blood Tumor Burden.
Authors: Duvic Madeleine , Kim Youn H , Kuzel Timothy M , Pacheco Theresa R , Foss Francine M , Parker Sareeta , Rizvi Syed , Chen Cong , Arduino Jean Marie , Olsen Elise A. 
Published: October 2019

Abstract
Abstract 1709
Poster Board I-735

Background
Vorinostat (Zolinza®) is an oral histone deacetylase inhibitor licensed by the United States Food and Drug Administration for the treatment of cutaneous manifestations of CTCL in pts with progressive and persistent disease on or following two prior systemic therapies. In a pivotal Phase IIB, open-label, multicenter trial in pts with advanced CTCL, vorinostat was well tolerated and associated with an overall response rate of 29.7% and a 29.5% response rate in pts with ≥Stage IIB disease. CTCL pts with a high blood tumor burden have a poorer prognosis and treatment of these pts represents an unmet medical need.

Aim
This post hoc analysis of the pivotal trial of vorinostat in CTCL assesses its potential effectiveness in treating systemic disease in pts with high blood tumor burden.

Methods
Pts with advanced CTCL received oral vorinostat 400 mg daily until disease progression or intolerable toxicity. Eligible pts had received ≥2 prior systemic therapies that included bexarotene unless intolerable. Pts were characterized as having a high blood tumor burden if at baseline they had counts of CD4+/CD26- cells >1000 per μL by flow, and additionally, Sézary syndrome (SS) pts were also required to have >80% erythroderma at the time of study entry. The tumor response in the blood and skin were examined. An objective blood response was defined as a ≥50% decrease in blood tumor burden and progression as a ≥25% increase from baseline. An objective response in the skin was defined as ≥50% reduction in mSWAT score from baseline assessment.

Results
Of 74 pts who entered the trial, 18 of 19 had a high blood tumor burden and were evaluable for this analysis. Of these 18, SS was present in 11 pts. Overall, an objective blood response was observed in 28% (5/18) of pts and an objective skin response in 44% (8/18) pts. An objective response in both blood and skin was observed in 17% (3/18) pts. The median change in blood tumor burden for all 11 SS pts was a 35% decrease (range: 23% increase - 94% decrease). An objective response in both the blood and skin was observed in 1 pt with SS who had a 76% decrease in CD4+/CD26- cells and a 99% reduction in mSWAT scores with a time to response of 115 and 28 days, respectively. An objective response in the blood alone was observed in 18% (2/11) of pts with SS with a decrease of 51% and 94% CD4+/CD26- cells and a time to response of 43 and 114 days, respectively. The skin response in these pts was a 30% and 17% reduction in mSWAT scores with a time to response of 28 and 142 days, respectively. Three of the 11 pts (27%) with SS had an objective response in the skin alone with changes in mSWAT score of 51%, 53%, and 58%, and a time to response of 28, 87, and 142 days, respectively. The changes in blood tumor burden in these pts were −35%, −13%, and +23%. The median change in blood tumor burden for the 7 pts not meeting criteria for SS was a 39% decrease (1 pt with a 327% increase and 6 pts with 6%-62% decrease). For these pts not meeting criteria for SS, an objective blood response was observed in 29% (2/7) pts and each of these pts had an objective skin response with a 50% and 62% decrease in CD4+/CD26- cells and a 63% and 67% reduction in mSWAT scores, respectively. The time to blood response was 233 and 205 days and to skin response was 114 and 171 days, respectively. An objective response in the skin alone was observed in 43% (3/7) non-SS pts with decreases in mSWAT score ranging from 61%-81% with a time to response of 29-85 days. The changes in blood tumor burden for these 3 pts were −49%, −24%, and +327%.

Conclusion
These results demonstrate the potential effectiveness of vorinostat in reducing not only the skin but the blood tumor burden in pts with CTCL and SS. Further study in prospective clinical trials is necessary to expand on these findings.

Disclosures
Duvic: Merck: Honoraria, Research Funding, Speakers Bureau. Kim:Merck: Membership on an entity's Board of Directors or advisory committees; Eisai: Membership on an entity's Board of Directors or advisory committees. Kuzel:Merck: Membership on an entity's Board of Directors or advisory committees. Pacheco:Merck: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Foss:Gloucester: Consultancy; Eisai: Consultancy; Merck: Consultancy; Allos: Consultancy. Rizvi:Merck: Employment, Equity Ownership. Chen:Merck: Employment, Equity Ownership. Arduino:Merck: Employment, Equity Ownership. Olsen:Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.