Iodine-131 anti-B1 antibody radioimmunotherapy for B-cell lymphoma was previously reported to have substantial antitumor activity in B-cell non-Hodgkin's lymphoma (NHL) after failures of standard and salvage chemotherapy. In this article, the University of Michigan Phase I clinical experience is updated, with follow-up of up to 6 yr since initial treatment reported.
Methods: Thirty-four patients with CD20-expressing NHL were first studied with one or more dosimetric doses of approximately 5 mCi of 1311 anti-B1 antibody (after varying predoses of unlabeled anti-B1 antibody). They were then treated with a patient-specific radioimmunotherapeutic dose designed to deliver a specified radiation dose to the whole body of between 25 and 85 cGy. Patients were observed for toxicity and tumor response.
Results: Seventeen (50%) patients had low-grade NHL, 9 (26%) had low-grade transformed NHL and 8 (24%) had de novo intermediate-grade NHL. At study entry, 17 (50%) had an elevated lactate dehydrogenase level, 12 (35%) had high tumor burden and 18 (53%) had not responded to their last chemotherapy. The median number of prior NHL therapies was 4.1. Twenty-eight of 34 patients completed treatment, with 22 of 28 (79%) achieving a response and 14 of 28 (50%) achieving a complete response (CR). The median duration of response was 357 days. The median duration of response for CRs was 471 days, with 4 CRs having a duration of > 1000 days (maximum = > 1460 days). Bone marrow toxicity was dose-limiting and dependent on the total-body dose (TBD) of radiation. Thrombocytopenia appeared to be more marked in patients with prior bone marrow transplantation. The TBD of 75 cGy was established as the maximum tolerated dose in patients who had not had prior bone marrow transplantation. Duration of CR was significantly longer (p < 0.04) in patients who received a TBD of 65-75 cGy (1109 days) than it was in those who received a lower TBD of 25-60 cGy (385 days). Four of 34 (12%) patients developed detectable human antimouse antibody levels. The median survival from study entry for all patients was 1508 days (range = 63 to >2226 days). Sixteen of 17 patients who achieved a response of > or = 6 mo duration remain alive.
Conclusion: This update of the Phase I results after 1311 anti-B1 antibody treatment for NHL indicates that CRs can be durable and that survival can be of long duration. This form of therapy for NHL should have increasing application in clinical practice after confirmation of these results in larger multicenter studies.