title: Pegylated recombinant interferon alpha-2b vs recombinant interferon alpha-2b for the initial treatment of chronic-phase chronic myelogenous leukemia: a phase III study.
abstract: Recombinant interferon alpha-2b (rIFN-alpha2b) is an effective therapy for chronic-phase chronic myelogenous leukemia (CML). Polyethylene glycol-modified rIFN-alpha2b is a novel formulation with a serum half-life ( approximately 40 h) compatible with once-weekly dosing. This open-label, noninferiority trial randomized 344 newly diagnosed CML patients: 171 received subcutaneous pegylated rIFN-alpha2b (6 microg/kg/week); 173 received rIFN-alpha2b (5 million International Units/m2/day). Primary efficacy end point was the 12-month major cytogenetic response (MCR) rate (<35% Philadelphia chromosome-positive cells). Modified efficacy analysis included all MCRs >12 months, except for patients discontinuing treatment after 6 months and achieving an MCR on other salvage therapy. The MCR rates were 23% for pegylated rIFN-alpha2b vs 28% for rIFN-alpha2b in the primary efficacy analysis and 26 vs 28% in the prospectively modified efficacy analysis. However, a significant imbalance in baseline hematocrit (HCT), a significant predictor of cytogenetic response (P=0.0001), was discovered: 51 (30%) patients treated with pegylated rIFN-alpha2b had low HCT (<33%) vs 33 (19%) rIFN-alpha2b-treated patients. Among patients with HCT >33%, the MCR rate was 33 vs 31%. The adverse event profile of weekly pegylated rIFN-alpha2b was comparable to daily rIFN-alpha2b. Once-weekly pegylated rIFN-alpha2b is an active agent for the treatment of newly diagnosed CML with an efficacy and safety profile similar to daily rIFN-alpha2b, although statistical noninferiority was not demonstrated.
authors.affiliation: Hôpital Edouard Herriot, Lyon, France. mauricette.michallet@chu-lyon.fr
authors.forename: M
authors.initials: M
authors.lastname: Michallet
authors.forename: F
authors.initials: F
authors.lastname: Maloisel
authors.forename: M
authors.initials: M
authors.lastname: Delain
authors.forename: A
authors.initials: A
authors.lastname: Hellmann
authors.forename: A
authors.initials: A
authors.lastname: Rosas
authors.forename: R T
authors.initials: RT
authors.lastname: Silver
authors.forename: C
authors.initials: C
authors.lastname: Tendler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004334:Drug Administration Schedule; D005260:Female; D006400:Hematocrit; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000633:toxicity; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D016019:Survival Analysis; D013810:Therapeutic Equivalency; D016896:Treatment Outcome
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a