Milestones in the development of Lym-1 therapy

Lym-1, a monoclonal antibody (MAb) that preferentially targets malignant ly mphocytes, has induced therapeutic remissions in patients with advanced non -Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia (CLL) when labele d with iodine-131 (I-131). Based on the strategy of fractionating the total radiation dose, trials were designed to define the safety, toxicity, and e fficacy of a series of doses of I-131-Lym-1 given 2-6 weeks apart. All pati ents had disease resistant to standard therapy,I-131-lym-1 was given after unconjugated Lym-1 and the I-131 dose was escalated in phase I-II trials. T herapy proved safe. The dose-limiting toxicity was thrombocytopenia, Nonhem atological toxicities did not exceed grade 2 except for infrequent instance s of grade 3 hypotension, In a low-dose (LD) trial of I-131-Lym-1, tumor re gression occurred in 25 (83%) of 30 patients and 17 (57%) had durable remis sions; 3 of the remissions were complete. In a maximum tolerated dose (MTD) trial of I-131-Lym-1, 10 (71%) of 14 entries that received at least two do ses of I-131-Lym-1 therapy and 11 (52%) of 21 total entries had remissions; 7 of the remissions were complete, All 3 entries in the MTD cohort of 100 mCi/m(2) [3.7 MBq/m(2)] of body surface area had durable complete remission s. Therapeutic remission and human anti-mouse antibody (HAMA) after Lym-1 t herapy were associated with increased survival that was significant in mult ivariate analyses. Evidence for an Ab3 idiotypic network with an antibody c ytotoxic for Raji human lymphoma was found in the only patient examined in detail thus far; this patient was studied because she had a high titer, HAM A and prolonged survival, In conclusion, I-131-Lym-1 induced durable remiss ions in patients with chemotherapy-resistant NHL or CLL and was associated with acceptable toxicity, In a subset of the patients, survival was quite p rolonged perhaps related to development of Ab3.