Maximum-tolerated dose, toxicity, and efficacy of 131I-Lym-1 antibody for fractionated radioimmunotherapy of non-Hodgkin's lymphoma

Purpose: Lym-1, a monoclonal antibody that preferentially targets malignant lymphocytes, has induced remissions in patients with non-Hodgkin's lymphoma (NHL) when labeled with iodine 131 (I-131). Based on the strategy of fractionating the total dose, this study was designed to define the maximum-tolerated dose (MTD) and efficacy of the first two, of a maximum of four, doses of I-131-Lym-1 given 4 weeks apart. Additionally, toxicity and radiation dosimetry were assessed. Materials and Methods: Twenty patients with advanced NHL entered the study a total of 21 rimes. Thirteen (62%) of the 21 entries had diffuse large-cell histologies. All patients had disease resistant to standard therapy and had received a mean of four chemotherapy regimens. I-131-Lym-l was given after Lym-l and I-131 was escalated in cohorts of patients from 40 to 100 mCi (1.5 to 3.7 GBq)/m(2) body surface area. Results: Mean radiation dose to the bone marrow from body and blood I-131 was 0.34 (range, 0.16 to 0.63) rad/mCi (0.09 mGy/MBq; range, 0.04 to 0.17 mGy/MBq). Dose-limiting toxicity was grade 3 to 4 thrombo cytopenia with an MTD af 100 mCi/m(2) (3.7 GBq/m(2)) for each of the first two doses of I-131-Lym-1 given 4 weeks apart. Nonhematologic toxicities did not exceed grade 2 except for one instance of grade 3 hypotension. Ten (71%) of 14 entries who received at least two doses of I-131-Lym-1 therapy and 11 (52%) of 21 total entries responded. Seven of the responses were complete, with a mean duration of 14 months. All three entries in the 100 mCi/m2 (3.7 MBq/m(2)) cohort held complete remissions (CRs). All responders had at least a partial remission (PR) after the first therapy dose of I-131-Lym-1. Conclusion: I-131-Lym-1 induced durable remissions in patients with NHL resistant to chemotherapy and was associated with acceptable toxicity. The nonmyeloablative MTD for each of the first two doses of I-131-Lym-1 was 100 mCi/m(2) (total, 200 mCi/m(2)) (3.7 GBq/m(2); total, 7.4 GBq/m(2)). (C) 1998 by American Society of Clinical Oncology.