Interim results for the phase II study of panobinostat (LBH589) in patients (Pts) with relapsed/refractory Hodgkin's lymphoma (HL) after autologous hematopoietic stem cell transplant (AHSCT).
2010; Lippincott Williams & Wilkins; Volume: 28; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2010.28.15_suppl.8007
ISSN1527-7755
AutoresAnna Sureda, Andreas Engert, Peter Browett, John Radford, G. Verhoef, Rod Ramchandren, N. Myke, Angela Shen, C. Le Corre, Anas Younes,
Tópico(s)Biochemical and Molecular Research
Resumo8007 Background: Panobinostat (PAN) is a pan-deacetylase inhibitor targeting epigenetic and non-epigenetic oncogenic pathways. In vitro, PAN decreases proliferation and induces apoptosis in HL cell lines at low nanomolar concentrations. In a Phase I study, promising activity was observed in pts with HL (EHA 2009, Abstract #1064). Methods: This international trial with Simon optimal 2-stage design has completed enrollment with 129 pts at 45 sites. Oral PAN is administered at a dose of 40 mg three times per week, every week, in 21-day cycles. Dose delay and modification is allowed for management of AEs. CT/MRI scans are conducted after every 2 cycles. Primary endpoint of the study is objective response rate. Secondary endpoints include time to and duration of response (TTR, DOR), PFS, and safety. Results: As of December 14, 2009, demographic data are available for 127 pts: median age was 32 years [18–75]; 37% had ≥5 prior lines of therapy; median prior regimen was 4 [2–6]; 37% had no response on last therapy; median time to relapse after first AHSCT was 8 months; 10 pts also had prior allogeneic transplant. In early analysis, 81 pts had ≥1 post baseline CT/MRI result available or discontinued early – 72% had tumor reduction, 5% had early PD, and 6% discontinued early (e.g. due to AE). 17 responses (2CR+15PR) have been reported; 14 of 17 responders continued on study, including 9 pts with DOR ranging from 12–52+ weeks. TTR ranged from 4–24 weeks. Median treatment duration for 127 pts was 78+ days [5–455+] and 64% of pts continued on treatment. 33% of pts have been treated for ≥8 cycles. Common G1/2 AEs were N/V/D, fatigue, anorexia, and neutropenia. Common related G3/4 AEs were thrombocytopenia (TCP) (55%) and anemia (11%). The TCP was reversible with dose hold or modification. No G3/4 QT prolongation has been reported. Conclusions: This is the first pivotal study initiated for a homogenous HL population in the post-transplant refractory/relapsed setting where there is no standard treatment. PAN is well tolerated and demonstrates encouraging activity in these heavily pretreated pts. Enrollment has been completed; updated results will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Abbott Laboratories, Amgen, Biogen Idec, Genentech, MethylGene, Novartis, Pharmion, Sandoz, sanofi-aventis, Seattle Genetics, Trubion, Xencor Education Concepts Group
Referência(s)