Panobinostat in patients with relapsed/refractory Hodgkin's lymphoma after autologous stem-cell transplantation: Results of a phase II study

Anas Younes, Anna Sureda, Dina Ben-Yehuda, Pier Luigi Zinzani, Tee Chuan Ong, H. Miles Prince, Simon J. Harrison, Mark Kirschbaum, Patrick Johnston, Jennifer Gallagher, Christophe Le Corre, Angela Shen, Andreas Engert

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Abstract

Purpose: Hodgkin's lymphoma (HL) has no standard of care for patients who are relapsed or refractory to autologous stem-cell transplantation (ASCT). This phase II study examined safety and activity of panobinostat in this population. Patients and Methods: Panobinostat 40 mg was administered orally three times per week. The primary end point was objective response rate (ORR) based on investigator assessment of radiologic imaging. Secondary end points included ORR by independent central review, time to response (TTR), duration of response (DOR), progression-free survival (PFS), overall survival, and safety. Exploratory biomarker analyses were performed. Results: The 129 treated patients (median age, 32 years; range, 18 to 75 years) were heavily pretreated with a median of four (range, two to seven) prior systemic regimens, and 41% did not respond to the regimen immediately preceding panobinostat. Tumor reductions occurred in 96 patients (74%). Objective response was achieved by 35 patients (27%), including 30 (23%) partial responses and five (4%) complete responses. The median TTR was 2.3 months, median DOR was 6.9 months, and median PFS was 6.1 months. The estimated 1-year overall survival rate was 78%. Common nonhematologic adverse events (AEs) - diarrhea, nausea, vomiting, and fatigue - were generally grade 1 and 2. Most common grade 3 and 4 hematologic AEs - thrombocytopenia, anemia, and neutropenia - were manageable. Early reductions in thymus and activation-regulated chemokine were observed in patients achieving complete or partial response. Conclusion: In the largest, prospective, multicenter, international trial conducted in heavily pretreated patients with HL who relapsed or were refractory to ASCT, panobinostat monotherapy demonstrated antitumor activity, resulting in durable responses.

Original languageEnglish (US)
Pages (from-to)2197-2203
Number of pages7
JournalJournal of Clinical Oncology
Volume30
Issue number18
DOIs
StatePublished - Jun 20 2012

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Younes, A., Sureda, A., Ben-Yehuda, D., Zinzani, P. L., Ong, T. C., Prince, H. M., Harrison, S. J., Kirschbaum, M., Johnston, P., Gallagher, J., Le Corre, C., Shen, A., & Engert, A. (2012). Panobinostat in patients with relapsed/refractory Hodgkin's lymphoma after autologous stem-cell transplantation: Results of a phase II study. Journal of Clinical Oncology, 30(18), 2197-2203. https://doi.org/10.1200/JCO.2011.38.1350