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 (¹³¹I). 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 ¹³¹I-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 times. 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. ¹³¹I-Lym-1 was given after Lym-1 and ¹³¹I was escalated in cohorts of patients from 40 to 100 mCi (1.5 to 3.7 GBq)/m² body surface area. Results: Mean radiation dose to the bone marrow from body and blood ¹³¹I 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 thrombocytopenia with an MTD of 100 mCi/m² (3.7 GBq/m²) for each of the first two doses of ¹³¹I-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 ¹³¹I-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/m²) cohort had complete remissions (CRs). All responders had at least a partial remission (PR) after the first therapy dose of ¹³¹I-Lym- 1. Conclusion: ¹³¹I-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 ¹³¹I-Lym-1 was 100 mCi/m² (total, 200 mCi/m²) (3.7 GBq/m²; total, 7.4 GBq/m²).