Phase 1 study of polyethylene glycol formulation of interferon α-2B (Schering 54031) in Philadelphia chromosome-positive chronic myelogenous leukemia

Interferon α (IFN-α) therapy improves prognosis in Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). Polyethylene glycol (PEG) attached to IFN-α prolongs its half-life and may offer better therapy. The aims of this phase 1 study were to define the maximal tolerated dose (MTD), dose-limiting toxicities (DLTs), and response with PEG IFN-α2b. Twenty-seven adults with Ph⁺ CML in chronic or accelerated phases, in whom IFN-α treatment had failed, were studied. Patients had hematologic (9 patients) or cytogenetic resistance (12 patients) or intolerance to IFN-α (6 patients). PEG IFN-α-2b was given as a weekly subcutaneous injection starting at 0.75 μg/kg weekly and escalating to 1.5, 3, 4.5, 6, 7.5, and 9.0 μg/kg. The MTD was defined at 7.5 to 9 μg/kg; DLT included severe fatigue, neurotoxicity, liver function abnormalities, and myelosuppression. Longer administration of PEG IFN-α-2b resulted in chronic side effects not observed earlier, which defined the MTD and DLT. The proposed phase 2 dose of PEG IFN-α-2b was 6 μg/kg weekly. Among 19 patients with active disease, 7 (37%) achieved complete hematologic response (CHR); 2 (11%) had a cytogenetic response (complete). Among 8 patients treated in CHR, 7 (87%) improved cytogenetic response to complete (4 patients) or partial (3 patients). All 6 patients intolerant to IFN-α tolerated PEG IFN-α-2b; 4 improved their cytogenetic response. The results show that PEG IFN-α-2b is easier to deliver (once weekly), better tolerated, and perhaps more effective than IFN-α.