Pharmacokinetics, dosimetry, and initial therapeutic results with 131I- and (111)In-/90Y-labeled humanized LL2 anti-CD22 monoclonal antibody in patients with relapsed, refractory non-Hodgkin's lymphoma.
The pharmacokinetics, dosimetry, and immunogenicity of 131I- and (111)In-/90Y-humanized LL2 (hLL2) anti-CD22 monoclonal antibodies were determined in patients with recurrent non-Hodgkin's lymphoma. Fourteen patients received tracer doses of 131I-hLL2 followed 1 week later by therapeutic doses intended to deliver 50-100 cGy to the bone marrow. Another eight patients received (111)In-hLL2 followed by therapy with 90Y-hLL2 also delivering 50 or 100 cGy to the bone marrow. The blood T(1/2) (hours) for the tracer infusions of 131I-hLL2 was 44.2 +/- 10.9 (mean +/- SD) compared with 54.2 +/- 25.0 for the therapy infusions, whereas the values were 70.7 +/- 17.6 for (111)In-hLL2 and 65.8 +/- 15.0 for 90Y-hLL2. The estimated average radiation dose from 131I-hLL2 in tumors >3 cm was 2.4 +/- 1.9 cGy/mCi and was only 0.9-, 1.0-, 1.1-, and 1.0-fold that of the bone marrow, lung, liver, and kidney, respectively. In contrast, the estimated average radiation dose from 90Y-hLL2 in tumors >3 cm was 21.5 +/- 10.0 cGy/mCi and was 3.7-, 2.5-, 1.8-, and 2.5-fold that of the bone marrow, lung, liver, and kidney, respectively. No evidence of significant anti-hLL2 antibodies was seen in any of the patients. Myelosuppression was the only dose-limiting toxicity and was greater in patients who had prior high-dose chemotherapy. Objective tumor responses were seen in 2 of 13 and 2 of 7 patients given 131I-hLL2 or 90Y-hLL2, respectively. In conclusion, 90Y-hLL2 results in a more favorable tumor dosimetry compared with 131I-hLL2. This finding, combined with the initial anti-tumor effects observed, encourage further studies of this agent in therapeutic trials.
Juweid
M E
ME
Garden State Cancer Center, Belleville, New Jersey 07109, USA. gscancer@att.net
Stadtmauer
E
E
Hajjar
G
G
Sharkey
R M
RM
Suleiman
S
S
Luger
S
S
Swayne
L C
LC
Alavi
A
A
Goldenberg
D M
DM
D000328:Adult; D000368:Aged; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D015815:Cell Adhesion Molecules; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D037102:Lectins; D008228:Lymphoma, Non-Hodgkin / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D012008:Recurrence; D051918:Sialic Acid Binding Ig-like Lectin 2; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D037102:Lectins; D051918:Sialic Acid Binding Ig-like Lectin 2; D015021:Yttrium Radioisotopes