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

Abstract

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.

Trial registration: ClinicalTrials.gov NCT01460940.

Keywords: Clinical trial; Hodgkin’s lymphoma; Lenalidomide; Panobinostat; Relapsed/refractory.

Conflict of interest statement

Disclosure

Novartis Pharmaceuticals provided panobinostat and Celgene Corporation provided lenalidomide for this trial. K.A. Blum, B. Christian, N.L. Bartlett, N.D. Wagner-Johnston, and T.A. Fehniger receive clinical trials support from Celgene and K.A. Blum receives clinical trials support from Novartis Pharmaceuticals. The remaining authors declare no competing financial interests.

Copyright © 2017 Elsevier Inc. All rights reserved.

Figures

Figure 1

Response Rates

Figure 2

Progression-Free Survival

Figure 3

Plasma Lenalidomide Concentrations Over Time