AN OPEN-LABEL, MULTICENTER STUDY OF POLYETHYLENE GLYCOL-L-ASPARAGINASE FOR THE TREATMENT OF ACUTE LYMPHOBLASTIC-LEUKEMIA

Background. L-asparaginase has been a mainstay of therapy along with v incristine and prednisone in the treatment of acute lymphoblastic leuk emia (ALL) in children for almost 30 years. Because L-asparaginase is a foreign protein, the potential exists for severe, dose-limiting hype rsensitivity reactions. To reduce this toxicity, L-asparaginase has be en linked with polyethylene glycol (PEG). Methods. Patients with ALL i n relapse were entered in a Phase II, open-label clinical trial (ASP-2 01A) to evaluate the toxicity and efficacy of PEG-L-asparaginase, PEG- L-asparaginase has demonstrated potential low immunogenicity and a pro longed plasma half-life relative to native enzyme. PEG-L-asparaginase (2000 IU/m(2) every 2 weeks) was used as single-agent induction therap y during an initial 14-day investigational window. Thereafter, the reg imen consisted of PEG-L-asparaginase, vincristine, and prednisone. Pat ients also were allowed to receive doxorubicin and intrathecal chemoth erapy beginning on day 14. All patients had been treated previously wi th one or more courses of native L-asparaginase; one of these patients was hypersensitive to L-asparaginase at enrollment.Results. During th e 14-day investigational window with PEG-L-asparaginase monotherapy, 2 2% of patients examined achieved a complete or partial remission. By c ompletion of the 35-day induction period, 78% (or 14 of 18) of evaluat ed patients achieved complete or partial remission. Anaphylaxis did no t occur during treatment. Mild urticaria and mild local allergic react ions occurred in five patients but did not cause discontinuation of tr eatment. The incidence of hyperglycemia and pancreatitis was less than expected from historic data published for previous studies with nativ e L-asparaginase. Conclusions. As administered in this study, PEG-L-as paraginase can be given safely with a spectrum of toxicity similar to that of native L-asparaginase. Single-agent activity was documented in patients with ALL in bone marrow relapse.