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Pooled analyses of two international, multicenter clinical studies of romidepsin in 167 patients with cutaneous T-cell lymphoma (CTCL)
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2009
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ImmunodeficienciesComposite EndpointImmunologyPathologyConfirmed CtclPharmacotherapyDermatologyImmunotherapyPrior Systemic TherapiesHematologyClinical TrialsMulticenter Clinical StudiesHealth SciencesLymphoid NeoplasiaAutoimmune DiseaseClinical TherapeuticImmune SurveillanceAutoimmunityDermatopathologyCutaneous T-cell LymphomaPooled AnalysesTherapeutic EfficacyAdult T-cell Leukemia-lymphomaMedicine
8546 Background: Romidepsin is a novel pan-HDAC inhibitor with demonstrated single-agent activity in 2 open-label clinical studies of 167 patients (pts) with CTCL [mycosis fungoides or Sézary Syndrome (SS)]. Data for these 2 studies were pooled for more accurate estimates of endpoints and investigation of subpopulations. Methods: GPI-04–0001 (pivotal study) enrolled 96 pts with confirmed CTCL who had recieved ≥1 prior systemic therapy. NCI 1312 (supportive study) enrolled 71 pts with CTCL. Pts recieved romidepsin, 14mg/m 2 as a 4-hr infusion on days 1, 8, and 15 every 28 days until disease progression (≥25% increase). The primary efficacy endpoint for both studies was overall response rate (ORR) using a composite endpoint that included skin assessment, lymph node and visceral involvement and abnormal circulating T-cells/Sézary cells. Results: 167 pts received romidepsin (as-treated); 135 pts (81%) were in the efficacy evaluable population. Mean age was 57±12 yrs, 67% men, 87% white. 103 pts (76%) had stage ≥IIB disease. Median number of prior systemic therapies was 2 (range 1–8). ORR in the table. Responses were noted in: 42% of pts with stage ≥IIB; 11 (58%) of 19 pts with SS (erythroderma + Sézary cells, >1000/ml or >20% ); and 20 (38%) of 52 pts who received prior bexarotene and 8 (40%) of 20 pts who had received denileukin diftitox. Most common drug-related adverse events (AE), all grades, included: nausea (67%), fatigue (49%), anorexia (37%), ECG T-wave changes (29%), anemia (26%), dysgeusia (23%), neutropenia (22%), leucopenia (20%). Related serious AEs in 2% of pts: supraventicular arrhythmia, ventricular arrhythmia, infection, neutropenia, WBC decreased, hyperuricemia, hypotension; all other serious AEs in ≤1 pt. 3 deaths reported as possibly related. Conclusions: Romidepsin is a valuable new therapy for pts with CTCL based on the ORR, CR, durability of response, improvement in all disease compartments and responses at all stages and in all subpopulations analyzed. [Table: see text] [Table: see text]