Treatment of refractory Hodgkin's lymphoma patients with an anti-CD25 ricin A-chain immunotoxin

The anti-CD25 immunotoxin RFT5.dgA was constructed by coupling the monoclon al antibody RFT5 via a sterically hindered disulfide linker to deglycosylat ed ricin A-chain and was administered to patients with relapsed Hodgkin's l ymphoma in four bolus infusions over 7 days (day 1, 3, 5 and 7). The maximu m tolerated dose in these patients as defined in a previous phase I study w as 15 mg/m(2). Subsequently, further patients were enrolled at the maximum tolerated dose and a total of 18 patients were treated at this level. All p atients had signs of progressive disease and were heavily pretreated. Side- effects in this trial were moderate and related to vascular leak syndrome. Five of 18 patients experienced NCI grade III toxicities including weakness , edema, dyspnea, and myalgia, Eleven of 16 (69%) patients receiving two or more cycles produced human anti-ricin antibodies and human anti-mouse anti bodies (greater than or equal to 1.0 mu g/ml). Seventeen of 18 patients wer e evaluable for clinical response. These included two partial remissions. O ne patient demonstrated minor response and five patients stable diseases. W e conclude that RFT5.dgA is of moderate clinical efficacy in this group of heavily pretreated refractory patients.