title: Panobinostat in patients with relapsed/refractory Hodgkin's lymphoma after autologous stem-cell transplantation: results of a phase II study.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: MD Anderson Cancer Center, 1515 Holcombe Blvd, Unite 429, Houston, TX 77030, USA. ayounes@mdanderson.org
authors.forename: Anas
authors.initials: A
authors.lastname: Younes
authors.forename: Anna
authors.initials: A
authors.lastname: Sureda
authors.forename: Dina
authors.initials: D
authors.lastname: Ben-Yehuda
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Zinzani
authors.forename: Tee-Chuan
authors.initials: TC
authors.lastname: Ong
authors.forename: H Miles
authors.initials: HM
authors.lastname: Prince
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Harrison
authors.forename: Mark
authors.initials: M
authors.lastname: Kirschbaum
authors.forename: Patrick
authors.initials: P
authors.lastname: Johnston
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gallagher
authors.forename: Christophe
authors.initials: C
authors.lastname: Le Corre
authors.forename: Angela
authors.initials: A
authors.lastname: Shen
authors.forename: Andreas
authors.initials: A
authors.lastname: Engert
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000628:therapy; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D007211:Indoles; D008297:Male; D000077767:Panobinostat; D012008:Recurrence; D019233:Retreatment; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D007211:Indoles; D000077767:Panobinostat