Phase II study of the histone deacetylase inhibitor panobinostat (LBH589) in patients with low or intermediate-1 risk myelodysplastic syndrome

A phase II non-randomized single arm trial of oral panobinostat (LBH589) was conducted in patients with low or intermediate-1 risk myelodysplastic syndrome (MDS). The objective of this study was to determine the clinical efficacy, safety, and tolerability of panobinostat in this patient population. The study would stop early if there was a chance >99% that the average overall response rate was <15%. Thirteen patients were treated: Median age was 70 years (range 47-84), 70% were transfusion dependent, 70% had intermediate-1 risk MDS. Most patients were diploid but one patient with del(5q), one with trisomy 8, one with complex cytogenetics, and two with deletion of 20q were included. Approximately 40% had previous therapy for MDS. Of the 13 patients, 1 (8%) achieved hematological improvement (HI-E and HI-P, duration 3 months) and 6 (46%) had stable disease for a median duration of 6 months (range 1.7-13.6). Treatment was withheld in one patient because of QTc prolongation but no other serious adverse effects were otherwise observed. Panobinostat did not consistently induce histone acetylation as measured with Western blot. This data indicates that panobinostat at the dose and schedule studied here has limited activity in lower risk MDS.