title: Low- versus high-dose radioimmunotherapy with humanized anti-CD22 or chimeric anti-CD20 antibodies in a broad spectrum of B cell-associated malignancies.
abstract: Both CD22 and CD20 have been used successfully as target molecules for radioimmunotherapy (RAIT) of low-grade B cell non-Hodgkin's lymphoma. Because both CD20 and CD22 are highly expressed relatively early in the course of B cell maturation, and because its expression is maintained up to relatively mature stages, we studied the potential of the humanized anti-CD22 antibody, hLL2, as well as of the chimeric anti-CD20 (chCD20) antibody, rituximab (IDEC-C2B8), for low- or high-dose (myeloablative) RAIT of a broad range of B cell-associated hematological malignancies. A total of 10 patients with chemorefractory malignant neoplasms of B cell origin were studied with diagnostic (n = 5) and/or potentially therapeutic doses (n = 9) of hLL2 (n = 4; 0.5 mg/kg, 8-315 mCi of 131I) or chCD20 (n = 5; 2.5 mg/kg, 15-495 mCi of 131I). The diagnostic doses were given to establish the patients' eligibility for RAIT and to estimate the individual radiation dosimetry. One patient suffered of Waldenström's macroglobulinemia, eight patients had low- (n = 4), intermediate- (n = 2) or high- (n = 2) grade non-Hodgkin's lymphoma, and one patient had a chemorefractory acute lymphatic leukemia, after having failed five heterologous bone marrow or stem cell transplantations. Three of these 10 patients were scheduled for treatment with conventional (30-63 mCi, cumulated doses of up to 90 mCi of 131I) and 7 with potentially myeloablative (225-495 mCi of 131I) activities of 131I-labeled hLL2 or chCD20 (0.5 and 2.5 mg/kg, respectively); homologous (n = 6) or heterologous (n = 1) stem cell support was provided in these cases. Good tumor targeting was observed in all diagnostic as well as posttherapeutic scans of all patients. In myeloablative therapies, the therapeutic activities were calculated based on the diagnostic radiation dosimetry, aiming at lung and kidney doses < or = 20 Gy. Stem cells were reinfused when the whole-body activity retention fell below 20 mCi. In eight assessable patients, five had complete remissions, two experienced partial remissions (corresponding to an overall response rate of 87%), and one (low-dose) patient had progressive disease despite therapy. In the five assessable, actually stem-cell grafted patients, the complete response rate was 100%. Both CD20 and CD22 seem to be suitable target molecules for high-dose RAIT in a broad spectrum of hematological malignancies of B cell origin with a broad range of maturation stages (from acute lymphatic leukemia to Waldenström's macroglobulinemia). The better therapeutic outcome of patients undergoing high-dose, myeloablative RAIT favors this treatment concept over conventional, low-dose regimens.
authors.affiliation: Department of Nuclear Medicine, Georg-August-University of Göttingen, Germany. tmbehr@med.uni-goettingen.de
authors.forename: T M
authors.initials: TM
authors.lastname: Behr
authors.forename: B
authors.initials: B
authors.lastname: Wörmann
authors.forename: M
authors.initials: M
authors.lastname: Gramatzki
authors.forename: J
authors.initials: J
authors.lastname: Riggert
authors.forename: S
authors.initials: S
authors.lastname: Gratz
authors.forename: M
authors.initials: M
authors.lastname: Béhé
authors.forename: F
authors.initials: F
authors.lastname: Griesinger
authors.forename: R M
authors.initials: RM
authors.lastname: Sharkey
authors.forename: H J
authors.initials: HJ
authors.lastname: Kolb
authors.forename: W
authors.initials: W
authors.lastname: Hiddemann
authors.forename: D M
authors.initials: DM
authors.lastname: Goldenberg
authors.forename: W
authors.initials: W
authors.lastname: Becker
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D018951:Antigens, CD20 / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D015815:Cell Adhesion Molecules; D005260:Female; D006801:Humans; D037102:Lectins; D016393:Lymphoma, B-Cell / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D008875:Middle Aged; D016499:Radioimmunotherapy; D011879:Radiotherapy Dosage; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D051918:Sialic Acid Binding Ig-like Lectin 2
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D037102:Lectins; D011993:Recombinant Fusion Proteins; D051918:Sialic Acid Binding Ig-like Lectin 2