Characterization of Cyclic Hematologic Changes Observed in Patients with Cutaneous T-Cell Lymphoma (CTCL) Receiving Romidepsin, a Novel Histone Deacetylase (HDAC) Inhibitor

• Published in: Blood 2009-11, Vol.114 (22), p.3701-3701
• Main Authors: Whittaker, Sean, Kim, Ellen J, Prince, Miles, Demierre, Marie France, Giver, Cynthia, Lonial, Sagar, Piekarz, Richard, Kim, Youn H, Nichols, Jean, Nix, Darrell, Bates, Susan
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V114.22.3701.3701

Abstract 3701 Poster Board III-637 Romidepsin is an anti-neoplastic agent that has been identified as a novel pan-HDAC inhibitor with single-agent activity in T-cell lymphoma. In a combined analysis of 167 patients (pts) with cutaneous T-cell lymphoma (CTCL) from 2 clinical studies (GPI and NCI studies), the overall response rate was 35%, including 10 pts with a complete clinical response (CCR). Median duration of response was 13.8 months and 42% of pts with advanced disease (stage ≥IIB) responded [Demierre et al. J Clin Oncol 27:15s, 2009 (suppl; abstr 8546)]. The most common hematologic abnormalities in these pts included anemia (41%), thrombocytopenia (34%), neutropenia (27%), and lymphopenia (26%). Most hematologic toxicities were Grade 1 or 2, although 'Grade 3 events were observed. These events were reversible and a small portion of the patients discontinued the study drug because of these events (2%). This report details an analysis of platelet counts in pts receiving romidepsin and an investigation into the mechanism of thrombocytopenia in nonclinical studies. Pts with CTCL who received ≥1 prior systemic therapy failure and had an ECOG PS of 0-2 were enrolled in 2 single-arm, open-label, multicenter and international clinical studies. Treatment with QTc prolonging therapies or CYP34A inhibitors was prohibited and pts with significant cardiovascular abnormalities were excluded. Romidepsin at 14 mg/m2 was administered as a 4-hr IV infusion on days 1, 8, and 15 of a 28 day cycle. Nonclinical studies were conducted in mice to investigate the mechanism of romidepsin effects on platelets. Romidepsin was administered to female BALB/c mice at doses of 1 or 4 mg/kg by tail-vein injection on days 1, 5 and 9. Blood samples were collected every 2 days from alternating groups of mice to minimize effects of bleeding on platelet counts. In clinical studies, there is a mean decrease in platelet counts during the treatment period of each cycle, and a return to baseline levels or above between cycles observed in both clinical studies as described in the table below. No clinically meaningful change has been observed in the central tendency over 4 cycles of treatment in both studies. StudyMean (SD) Platelet counts x 109/LC1D11C1D8C2D1C2D8C3D1C3D8C4D1C4D8GPI287 (114)195 (96.6)306 (89.7)192 (71.5)312 (103)191 (65.1)300 (94.4)197 (68.3)NCI273 (102)166 (63.2)320 (113)166 (54.9)291 (76.9)175 (63.2)298 (69.2)171 (60.3)1Mean pretreatment baselines In the mouse studies, dose-