Safety and Efficacy of the Novel Combination of Panobinostat (LBH589) and Everolimus (RAD001) in Relapsed/Refractory Hodgkin and Non-Hodgkin Lymphoma,

Abstract 3718

Based on preclinical experiments that demonstrated in vitro synergism between pan-deacetylase (DAC) inhibitor Panobinostat (LBH589) with mTOR inhibitor Everolimus (RAD001) in Hodgkin and non-Hodgkin lymphoma cell lines, we conducted a phase I/II study to determine the safety and efficacy of this novel regimen. Patients were eligible if they had relapsed or refractory Hodgkin or non-Hodgkin lymphoma regardless of the number of prior regimens, including autologous and allogeneic transplantation. Everolimus was self administered orally daily and Panobinostat three times weekly on 4 dose escalation levels [Table 1]. To date, a total of 30 patients have been treated. The histologic subtypes include small lymphocytic (n=1), follicular (n=2), mantle cell (n=3), hodgkin (n=12), diffuse large B-cell (n=7), T-cell (n=3), one discordant Hodgkin/marginal zone lymphoma and one discordant Hodgkin/large cell lymphoma. The median number of prior therapies is 3 with 11 patients receiving prior autologous transplantation. 30 patients received at least 1 dose and are evaluable for safety and 28 are evaluable for response. The DLT was thrombocytopenia observed in the 4^th cohort with a dose of 30mg Panobinostat and 10mg of Everolimus. Therefore, 6 patients were treated at the lower dose level of 20mg Panobinostat and 10mg Everolimus which was determined to be the maximum tolerated dose (MTD) and starting dose in the phase II portion of the study. To date, 16 patients have been treated in the phase II portion of the study. Treatment side effects are manageable with the following grade 3/4 adverse events most commonly observed: thrombocytopenia 48%, neutropenia 48% and anemia 20%. One death occurred on study, possibly related to pulmonary embolus. 20 out of 28 evaluable patients (71%) had tumor reduction ranging from -12% to -72% of whom 50% had PR or CR. Our data demonstrate safety and promising clinical activity of this novel combination in a variety of lymphomas. The phase II portion continues to enroll patients to determine the efficacy of this novel regimen.