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

Joseph J. Maly, Beth A. Christian, Xiaohua Zhu, Lai Wei, Jennifer L. Sexton, Samantha M. Jaglowski, Steven M. Devine, Todd A. Fehniger, Nina D. Wagner-Johnston, Mitch A. Phelps, Nancy L. Bartlett, Kristie A. Blum

Research output: Contribution to journalArticlepeer-review

Abstract

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 and 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.

Original languageEnglish (US)
Pages (from-to)347-353
Number of pages7
JournalClinical Lymphoma, Myeloma and Leukemia
Volume17
Issue number6
DOIs
StatePublished - Jun 2017

Keywords

  • Clinical trial
  • Hodgkin's lymphoma
  • Lenalidomide
  • Panobinostat
  • Relapsed/refractory

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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