PURPOSE:Thalidomide and lenalidomide can alleviate anemia in myelofibrosis. However, their value is undermined by their respective potential to cause peripheral neuropathy and myelosuppression. We therefore evaluated the safety and therapeutic activity of another immunomodulatory drug, pomalidomide. METHODS: In a phase II randomized, multicenter, double-blind, adaptive design study, four treatment arms were evaluated: pomalidomide (2 mg/d) plus placebo, pomalidomide (2 mg/d) plus prednisone, pomalidomide (0.5 mg/d) plus prednisone, and prednisone plus placebo. Pomalidomide was administered for up to 12 28-day treatment cycles. Prednisone (30 mg/d) was given in a tapering dose schedule during the first three cycles. Response was assessed by International Working Group criteria. RESULTS:Eighty-four patients with myelofibrosis-associated anemia were randomly assigned to the aforementioned treatment arms: 22, 19, 22, and 21, respectively. Response in anemia was documented in 20 patients, including 15 who became transfusion independent. Response rates in the four treatment arms were 23% (95% CI, 5% to 41%), 16% (95% CI, 0% to 33%), 36% (95% CI, 16% to 56%), and 19% (95% CI, 2% to 36%). The corresponding figures for patients receiving > or = 3 cycles of treatment (n = 62) were 38%, 23%, 40%, and 25%. Response to pomalidomide with or without prednisone was durable (range, 3.2 to 16.9+ months) and significantly better in the absence of leukocytosis (37% v 8%; P = .01); JAK2V617F or cytogenetic status did not affect response. Grade > or = 3 toxicities were infrequent and included (in each treatment arm) neutropenia (9%; 16%; 5%; 5%), thrombocytopenia (14%; 16%; 9%; 5%), and thrombosis (9%; 5%; 0%; 0%). CONCLUSION:Pomalidomide therapy at 0.5 or 2 mg/d with or without an abbreviated course of prednisone is well tolerated in patients with myelofibrosis and active in the treatment of anemia.
RCT Entities:
PURPOSE:Thalidomide and lenalidomide can alleviate anemia in myelofibrosis. However, their value is undermined by their respective potential to cause peripheral neuropathy and myelosuppression. We therefore evaluated the safety and therapeutic activity of another immunomodulatory drug, pomalidomide. METHODS: In a phase II randomized, multicenter, double-blind, adaptive design study, four treatment arms were evaluated: pomalidomide (2 mg/d) plus placebo, pomalidomide (2 mg/d) plus prednisone, pomalidomide (0.5 mg/d) plus prednisone, and prednisone plus placebo. Pomalidomide was administered for up to 12 28-day treatment cycles. Prednisone (30 mg/d) was given in a tapering dose schedule during the first three cycles. Response was assessed by International Working Group criteria. RESULTS: Eighty-four patients with myelofibrosis-associated anemia were randomly assigned to the aforementioned treatment arms: 22, 19, 22, and 21, respectively. Response in anemia was documented in 20 patients, including 15 who became transfusion independent. Response rates in the four treatment arms were 23% (95% CI, 5% to 41%), 16% (95% CI, 0% to 33%), 36% (95% CI, 16% to 56%), and 19% (95% CI, 2% to 36%). The corresponding figures for patients receiving > or = 3 cycles of treatment (n = 62) were 38%, 23%, 40%, and 25%. Response to pomalidomide with or without prednisone was durable (range, 3.2 to 16.9+ months) and significantly better in the absence of leukocytosis (37% v 8%; P = .01); JAK2V617F or cytogenetic status did not affect response. Grade > or = 3 toxicities were infrequent and included (in each treatment arm) neutropenia (9%; 16%; 5%; 5%), thrombocytopenia (14%; 16%; 9%; 5%), and thrombosis (9%; 5%; 0%; 0%). CONCLUSION:Pomalidomide therapy at 0.5 or 2 mg/d with or without an abbreviated course of prednisone is well tolerated in patients with myelofibrosis and active in the treatment of anemia.
Authors: Linda Mileshkin; Richard Stark; Bruce Day; John F Seymour; Jerome B Zeldis; H Miles Prince Journal: J Clin Oncol Date: 2006-08-28 Impact factor: 44.544
Authors: Patrick A J Haslett; Paul Roche; C Ruth Butlin; Murdo Macdonald; Niraj Shrestha; Rakesh Manandhar; Joe Lemaster; Rachel Hawksworth; Mahesh Shah; A Steven Lubinsky; Matthew Albert; Jason Worley; Gilla Kaplan Journal: J Infect Dis Date: 2005-11-10 Impact factor: 5.226
Authors: S Vincent Rajkumar; Suzanne Hayman; Morie A Gertz; Angela Dispenzieri; Martha Q Lacy; Philip R Greipp; Susan Geyer; Nancy Iturria; Rafael Fonseca; John A Lust; Robert A Kyle; Thomas E Witzig Journal: J Clin Oncol Date: 2002-11-01 Impact factor: 44.544
Authors: Alan List; Gordon Dewald; John Bennett; Aristotle Giagounidis; Azra Raza; Eric Feldman; Bayard Powell; Peter Greenberg; Deborah Thomas; Richard Stone; Craig Reeder; Kenton Wride; John Patin; Michele Schmidt; Jerome Zeldis; Robert Knight Journal: N Engl J Med Date: 2006-10-05 Impact factor: 91.245
Authors: S A Schey; P Fields; J B Bartlett; I A Clarke; G Ashan; R D Knight; M Streetly; A G Dalgleish Journal: J Clin Oncol Date: 2004-07-12 Impact factor: 44.544
Authors: Carmen P Castaneda; Jerome B Zeldis; John Freeman; Curtis Quigley; Nancy A Brandenburg; Robert Bwire Journal: Drug Saf Date: 2008 Impact factor: 5.606
Authors: Tiziano Barbui; Giovanni Barosi; Gunnar Birgegard; Francisco Cervantes; Guido Finazzi; Martin Griesshammer; Claire Harrison; Hans Carl Hasselbalch; Rudiger Hehlmann; Ronald Hoffman; Jean-Jacques Kiladjian; Nicolaus Kröger; Ruben Mesa; Mary F McMullin; Animesh Pardanani; Francesco Passamonti; Alessandro M Vannucchi; Andreas Reiter; Richard T Silver; Srdan Verstovsek; Ayalew Tefferi Journal: J Clin Oncol Date: 2011-01-04 Impact factor: 44.544