Pegylated recombinant interferon alpha-2b vs recombinant interferon alpha-2b for the initial treatment of chronic-phase chronic myelogenous leukemia: a phase III study

Recombinant interferon alpha-2b (rIFN-α2b) is an effective therapy for chronic-phase chronic myelogenous leukemia (CML). Polyethylene glycol-modified rIFN-α2b is a novel formulation with a serum half-life (∼40 h) compatible with once-weekly dosing. This open-label, noninferiority trial randomized 344 newly diagnosed CML patients: 171 received subcutaneous pegylated rIFN-α2b (6 μg/kg/week); 173 received rIFN-α2b (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-α2b vs 28% for rIFN-α2b 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-α2b had low HCT (<33%) vs 33 (19%) rIFN-α2b-treated patients. Among patients with HCT >33%, the MCR rate was 33 vs 31%. The adverse event profile of weekly pegylated rIFN-α2b was comparable to daily rIFN-α2b. Once-weekly pegylated rIFN-α2b is an active agent for the treatment of newly diagnosed CML with an efficacy and safety profile similar to daily rIFN-α2b, although statistical noninferiority was not demonstrated.