Therapy of B-cell lymphomas with monoclonal antibodies and radioimmunoconjugates: the Seattle experience

Monoclonal antibodies (mAbs) and radioimmunoconjugates targeting B-cell differentiation antigens have emerged as promising new treatments for patients with relapsed non-Hodgkin's lymphoma. This review focuses on our experience in Seattle over the past decade treating relapsed B-cell non-Hodgkin's lymphomas. In initial pilot studies, we administered escalating doses of the unmodified murine anti-CD20 mAb 1F5 to four patients with multiply relapsed lymphoma and documented the dose-dependent penetration of antibody into the bone marrow and lymph nodes. The two patients who received the higher doses (1032 mg and 2380 mg) had remissions of brief duration, including one minor response lasting 2 weeks and one partial response lasting 6 weeks. Sequential phase-I and -II trials with myeloablative doses of iodine-131-mAbs have documented complete responses in 30 of 36 (83%) patients treated and, most importantly, many of these responses have been durable. A recent long-term follow-up study of the 29 patients treated with myeloablative doses of the I-131-labeled murine anti-B1 (anti-CD20) antibody has documented estimated overall and progression-ree survival rates of 68% and 42%, respectively, with a median follow-up time of 42 months. To optimize the durability of responses, we are currently conducting a phase-I/II trial studying the toxicity and efficacy of I-131-anti-B1 antibody given in combination with high-dose etoposide and cyclophosphamide and autologous hematopoietic stem cell rescue.