Pharmacokinetics, Dosimetry, and Initial Therapeutic Results with ¹³¹I- and ¹¹¹In-⁹⁰Y-Labeled Humanized LL2 Anti-CD22 Monoclonal Antibody in Patients with Relapsed, Refractory Non-Hodgkin's Lymphoma¹

The pharmacokinetics, dosimetry, and immunogenicity of ¹³¹I- and ¹¹¹In⁹⁰Y-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 ¹¹¹In-hLL2 followed by therapy with ⁹⁰Y-hLL2 also delivering 50 or 100 cGy to the bone marrow. The blood T_½ (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 ¹¹¹In-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.