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 monoclonal antibody RFT5 via a sterically hindered disulfide linker to deglycosylated ricin A-chain and was administered to patients with relapsed Hodgkin's lymphoma in four bolus infusions over 7 days (day 1, 3, 5 and 7). The maximum tolerated dose in these patients as defined in a previous phase I study was 15 mg/m2. Subsequently, further patients were enrolled at the maximum tolerated dose and a total of 18 patients were treated at this level. All patients 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 antibodies (>/=1.0 microg/ml). Seventeen of 18 patients were evaluable for clinical response. These included two partial remissions. One patient demonstrated minor response and five patients stable diseases. We conclude that RFT5.dgA is of moderate clinical efficacy in this group of heavily pretreated refractory patients. Leukemia (2000) 14, 129-135.
Schnell
R
R
Klinik I fuer Innere Medizin, Universitaet zu Koeln, Koeln, Germany.
Vitetta
E
E
Schindler
J
J
Borchmann
P
P
Barth
S
S
Ghetie
V
V
Hell
K
K
Drillich
S
S
Diehl
V
V
Engert
A
A
D006689:Hodgkin Disease / Q000628:therapy*; D006801:Humans; D000922:Immunotoxins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D012276:Ricin / Q000276:immunology*; D016896:Treatment Outcome
D000922:Immunotoxins; D015375:Receptors, Interleukin-2; D012276:Ricin