A PHASE-I ESCALATING-DOSE SAFETY, DOSIMETRY AND EFFICACY STUDY OF RADIOLABELED MONOCLONAL-ANTIBODY LYM-1

Thirteen patients with relapsed or refractory Non-Hodgkin's Lymphoma w ere treated with I-131-Lym-1 during the course of a dose escalation tr ial. Principal aims were to establish the maximum tolerated single dos e (MTD), as well as to assess clinical and dosimetric effects of the M TD. Patients were eligible if >25% of tumor cells bound Lym-1 on immun ohistochemistry, slain intensity was +2/4 or greater and human anti-mo use antibody (HAMA) assay was negative. Radioimmunotherapy was perform ed with escalating doses at levels of 50 mCi, 65 mCi/m2 and 80 mCi/m2 (50-139 mCi total). Patients were eligible for retreatment after 6-10 weeks if there was no severe toxicity, their disease was at least stab le and HAMA remained negative. Three were retreated. Four have achieve d partial responses which lasted 11, 11, 18 and 22 weeks. Acute toxici ties included rigors (69%), fever (62%), nausea (46%), vomiting (46%), pruritus (23%), urticaria (23%), chest pain (23%) and bronchospasm (1 5%). HAMA developed in 3 patients. Myelosuppression, manifested as thr ombocytopenia and neutropenia, was dose-limiting and defined the singl e dose MTD at 65 nCi/m2. Plasma radioactivity clearance was biphasic, with a 0.9 hr alpha-T1/2 and a 19.8 hr beta-T1/2. At completion of Lym -1 infusion, a mean of 45% of the injected dose was recoverable in the circulation. Images obtained within the first 2 hours indicated mean hepatic and splenic uptake was 29% and 11%, respectively. Radiation ab sorbed doses to tumor ranged from 18-61 rads; mean doses to whole body ranged from 17 to 71 rads.