Complete Remissions of Adult T-cell Leukemia with Anti-CD25 Recombinant Immunotoxin LMB-2 and Chemotherapy to Block Immunogenicity.

PURPOSE: Adult T-cell leukemia (ATL) is usually CD25(+) and rapidly fatal. Anti-CD25 recombinant immunotoxin LMB-2 had phase I activity limited by immunogenicity and rapid growth. To prevent antidrug antibodies and leukemic progression between cycles, a phase II trial was performed with LMB-2 after cyclophosphamide and fludarabine. EXPERIMENTAL DESIGN: ATL patients received cyclophosphamide and fludarabine days 1 to 3 and 2 weeks later began up to 6 cycles at 3-week intervals of cyclophosphamide and fludarabine days 1 to 3 followed by LMB-2 30-40 μg/kg i.v. days 3, 5, and 7. Three different dose levels of cyclophosphamide and fludarabine were used, 20+200 (n = 3), 25+250 (n = 12), and 30+300 mg/m(2) (n = 2). RESULTS: Of 17 patients enrolled and treated with fludarabine and cyclophosphamide for cycle-1, 15 received subsequent cycle(s) containing LMB-2 and were therefore evaluable for response. Lack of antibody formation permitted retreatment in most patients. Of 10 evaluable leukemic patients receiving 25+250 or 30+300 mg/m(2) of fludarabine and cyclophosphamide, 6 (60%) achieved complete remission (CR) and 2 (20%) partial remission (PR), and all 5 with >25% leukemic cells achieved CR. No responses were achieved in 5 with lymphomatous ATL or lower fludarabine and cyclophosphamide doses. Median CR duration for the 6 CRs was 40 weeks. One is without detectable ATL at 47 months. Toxicity was mostly attributable to fludarabine and cyclophosphamide. Capillary leak from LMB-2 was non-dose limiting. One patient in CR died of a preexisting infection. CONCLUSIONS: LMB-2, administered with fludarabine and cyclophosphamide to prevent antidrug antibodies and rapid intercycle progression, is highly effective in achieving CR in leukemia ATL. Fludarabine and cyclophosphamide dose/schedule is important for safety and efficacy in this high-risk population.