title: Results of a phase 2 trial of the single-agent histone deacetylase inhibitor panobinostat in patients with relapsed/refractory Waldenström macroglobulinemia.
abstract: The present study aimed to determine the safety and activity of the histone deacetylase inhibitor panobinostat in patients with relapsed/refractory Waldenström macroglobulinemia (WM). Eligibility criteria included patients with relapsed/refractory WM with any number of prior therapies. Patients received panobinostat at 30 mg 3 times a week; 12 of 36 (33%) patients were enrolled at 25 mg dose. A total of 36 patients received therapy. The median age was 62 years (range, 47-80) and the median number of prior therapies was 3 (range, 1-8). All of the patients had received prior rituximab. Minimal response (MR) or better was achieved in 47% of patients (90% confidence interval [CI], 33-62), with 22% partial remissions and 25% MR. In addition, 18 (50%) patients achieved stable disease and none showed progression while on therapy. The median time to first response was 1.8 months (range, 1.7-3.2). The median progression-free survival was 6.6 months(90% CI, 5.5-14.8). Grade 3 and 4 toxicities included thrombocytopenia (67%), neutropenia (36%), anemia (28%), leukopenia (22%), and fatigue (11%). We conclude that panobinostat is an active therapeutic agent in patients with relapsed/ refractory WM. This study (www.clinicaltrials.gov identifier: NCT00936611) establishes a role for histone deacetylase inhibitors as an active class of therapeutic agents in WM.
authors.affiliation: Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. irene_ghobrial@dfci.harvard.edu
authors.forename: Irene M
authors.initials: IM
authors.lastname: Ghobrial
authors.forename: Federico
authors.initials: F
authors.lastname: Campigotto
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Murphy
authors.forename: Erica N
authors.initials: EN
authors.lastname: Boswell
authors.forename: Ranjit
authors.initials: R
authors.lastname: Banwait
authors.forename: Feda
authors.initials: F
authors.lastname: Azab
authors.forename: Stacey
authors.initials: S
authors.lastname: Chuma
authors.forename: Janet
authors.initials: J
authors.lastname: Kunsman
authors.forename: Amanda
authors.initials: A
authors.lastname: Donovan
authors.forename: Farzana
authors.initials: F
authors.lastname: Masood
authors.forename: Diane
authors.initials: D
authors.lastname: Warren
authors.forename: Scott
authors.initials: S
authors.lastname: Rodig
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Edie
authors.initials: E
authors.lastname: Weller
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Matous
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D007075:Immunoglobulin M / Q000097:blood; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D000077767:Panobinostat; D012008:Recurrence; D016896:Treatment Outcome; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007075:Immunoglobulin M; D007211:Indoles; D000077767:Panobinostat