A Phase I/II Trial of Panobinostat in Combination With Lenalidomide in Patients With Relapsed or Refractory Hodgkin Lymphoma

On the basis of previous studies showing single-agent efficacy with lenalidomide and panobinostat in patients with relapsed or refractory Hodgkin lymphoma (HL), we conducted a phase I/II study to evaluate the safety arid efficacy of the combination in this patient population. The recommended phase II dose was 25 mg lenalidomide on days 1 to 21 with 15 mg panobinostat 3 times per week, and an overall response rate of 16.7% in patients was observed, with a durable response in 1 patient with lymphocyte-predominant HL. Background: Lenalidomide and panobinostat have shown single-agent efficacy of 14% to 50% and 27% to 58%, respectively, in Hodgkin lymphoma (HL). This phase I/II study was conducted to determine the maximum tolerated dose (MTD), safety, and efficacy of lenalidomide combined with panobinostat in relapsed/refractory HL. Patients and Methods: In the phase I trial, previously treated patients with classical or lymphocyte-predominant HL received escalating doses of lenalidomide on days 1 to 21 and panobinostat 3 times a week (TIW) every 28 days. Dose-limiting toxicity (DLT) was defined during cycle 1. When the MTD was determined, a phase II study was conducted to determine overall response (OR). Results: Twenty-four patients enrolled; 11 in the phase I and 13 in,phase II portions. No DLTs were observed but 2 patients who received 25 mg lenalidomide and 20 mg panobinostat experienced neutropenia and thrombocytopenia > 14 days in cycle 2, leading to selection of 25 mg lenalidomide on days 1 to 21 and 15 mg panobinostat TIW for the phase II dose. In all 24 patients, Grade 3 to 4 toxicities consisted of neutropenia (58%), thrombocytopenia (42%), lymphopenia (25%), and febrile neutropenia (25%). OR was 16.7% (2 complete response [CR] and 2 partial response). One patient with CR had lymphocyte-predominant HL and received 22 cycles. Median progression free survival and overall survival were 3.8 and 16.4 months, respectively. Conclusion: Although the combination of panobinostat and lenalidomide appears safe in patients with relapsed/refractory HL, the limited efficacy and significant rates of neutropenia and febrile neutropenia observed do not support further evaluation of this combination in HL.