Treatment of refractory Hodgkin's lymphoma patients with an iodine-131-labeled murine anti-CD30 monoclonal antibody.
OBJECTIVE
Hodgkin's lymphoma (HL) has been demonstrated to be a good target for immunotherapy since lymphocyte activation markers such as CD30 are expressed in high numbers on the malignant cells. Thus, we developed a new radioimmunoconjugate consisting of the murine anti-CD30 monoclonal antibody (MAb) Ki-4 labeled with iodine-131 ((131)I).


METHODS
The biodistribution of (131)I-Ki-4 was assessed via dosimetry after preinfusion of 5 mg native Ki-4 followed by 250 to 300 MBq (131)I-labeled Ki-4. Whole-body scintigraphy was performed 1 hour, 24 hours, 48 hours, 72 hours, and 6 days after the infusion. Dosimetry was calculated using the programs NucliDose ICON-IDL (version 5.0.2; Siemens, Erlanger, Germany) and MIRDOSE (version 3.1; Oak Ridge National Laboratories; Oak Ridge, TN). The therapeutic dose was given on day 8 after preinfusion of unlabeled Ki-4.


RESULTS
We treated 22 patients with relapsed or refractory CD30-positive HL. Preinfusion of 5 mg native Ki-4 was sufficient to bind the soluble CD30. Imaging demonstrated localization of involved areas measuring 5 cm in diameter or more in four patients and 2.5 cm in one patient. Patients received total body doses of 0.035 Gy to 0.99 Gy. Acute toxicity was mild with grade 1 fatigue in 19 of 22 assessable patients. Seven patients experienced grade 4 degrees hematotoxicity 4 to 8 weeks after treatment. Response included one complete remission, five partial remissions, and three minor responses.


CONCLUSIONS
Treatment with (131)I-Ki-4 is effective but can be associated with severe hematotoxicity.
Schnell
Roland
R
Department of Internal Medicine I, Department of Nuclear Medicine, University of Cologne, Germany.
Dietlein
Markus
M
Staak
Jan Oliver
JO
Borchmann
Peter
P
Schomaecker
Klaus
K
Fischer
Thomas
T
Eschner
Wolfgang
W
Hansen
Hinrich
H
Morschhauser
Franck
F
Schicha
Harald
H
Diehl
Volker
V
Raubitschek
Andrew
A
Engert
Andreas
A
D000293:Adolescent; D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use* / Q000633:toxicity; D006689:Hodgkin Disease / Q000628:therapy*; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods*; D007457:Iodine Radioisotopes; D017730:Ki-1 Antigen / Q000276:immunology*; D051379:Mice; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D007457:Iodine Radioisotopes; D017730:Ki-1 Antigen