Treatment of refractory Hodgkin's lymphoma patients with an iodine-131-labeled murine anti-CD30 monoclonal antibody

被引:82
作者
Schnell, R
Dietlein, M
Staak, JO
Borchmann, P
Schomaecker, K
Fischer, T
Eschner, W
Hansen, H
Morschhauser, F
Schicha, H
Diehl, V
Raubitschek, A
Engert, A
机构
[1] Univ Cologne, Innere Med Klin 1, Dept Nucl Med, Dept Internal Med 1, D-50924 Cologne, Germany
[2] Ctr Hosp Reg & Univ Lille, Hop Huriez, F-59037 Lille, France
[3] City Hope Natl Med Ctr, Dept Radioimmunotherapy, Duarte, CA 91010 USA
关键词
D O I
10.1200/JCO.2005.09.098
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose 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 (I-131). Patients and Methods The biodistribution of I-131-Ki-4 was assessed via dosimetry after preinfusion of 5 mg native Ki-4 followed by 250 to 300 MBq I-131-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 m-g 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. Conclusion Treatment with I-131-Ki-4 is effective but can be associated with severe hematotoxicity.
引用
收藏
页码:4669 / 4678
页数:10
相关论文
共 53 条
[1]  
AGNARSSON BA, 1989, CANCER, V63, P2083, DOI 10.1002/1097-0142(19890601)63:11<2083::AID-CNCR2820631102>3.0.CO
[2]  
2-U
[3]  
BARLETT NL, 2002, BLOOD, V100
[4]   YTTRIUM-90-LABELED ANTIFERRITIN FOLLOWED BY HIGH-DOSE CHEMOTHERAPY AND AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR POOR-PROGNOSIS HODGKINS-DISEASE [J].
BIERMAN, PJ ;
VOSE, JM ;
LEICHNER, PK ;
QUADRI, SM ;
ARMITAGE, JO ;
KLEIN, JL ;
ABRAMS, RA ;
DICKE, KA ;
VRIESENDORP, HM .
JOURNAL OF CLINICAL ONCOLOGY, 1993, 11 (04) :698-703
[5]  
BONADONNA G, 1982, CANCER TREAT REP, V66, P881
[6]  
Borchmann P, 2000, BLOOD, V96, p730A
[7]   The human anti-CD30 antibody 5F11 shows in vitro and in vivo activity against malignant lymphoma [J].
Borchmann, P ;
Treml, JF ;
Hansen, H ;
Gottstein, C ;
Schnell, R ;
Staak, O ;
Zhang, HF ;
Davis, T ;
Keler, T ;
Diehl, V ;
Graziano, RF ;
Engert, A .
BLOOD, 2003, 102 (10) :3737-3742
[8]   INDICATIONS FOR AUTOLOGOUS BONE-MARROW TRANSPLANTATION IN HODGKINS-DISEASE [J].
CARELLA, AM .
LEUKEMIA & LYMPHOMA, 1992, 7 :21-22
[9]   Radioimmunotherapy of non-Hodgkin lymphomas [J].
Cheson, BD .
BLOOD, 2003, 101 (02) :391-398
[10]   CD30 in normal and neoplastic cells [J].
Chiarle, R ;
Podda, A ;
Prolla, G ;
Gong, J ;
Thorbecke, GJ ;
Inghirami, G .
CLINICAL IMMUNOLOGY, 1999, 90 (02) :157-164