High Dose Radiolabeled Antibody Therapy of Lymphoma1

A trial has been initiated testing the effects of high dose radiolabeled monoclonal antibody administered in conjunction with marrow transplan tation for treatment of lymphoma. This study is based on observations in mice demonstrating that radiolabeled antibody against a normal lympho cyte-associate antigen can induce regression of lymphoma masses. These preclinical studies also showed that large amounts of antibody are needed to achieve adequate biodistribution in vivo and that potentially curative doses of radionuclide induce substantial hematopoietic toxicity. Conse quently, in patients with recurrent lymphoma, we are first evaluating the influence of dose on the biodistribution of a pan B-cell antibody, MB-1 (anti-CD37). In four patients, the biodistribution studies indicated that at the highest amount of antibody tested i:"I-labeled antibody MB-1 (10 mg/kg) could deliver more radiation to tumor than to normal organs. These patients were treated with antibody MB-1 labeled with 250 to 482 mCi '"I estimated to deliver 380 to 1570 cGy to normal organs and 850 to 4260 cGy to tumor. Myelosuppression occurred in all patients and required infusion of cryopreserved marrow in one patient. Complete tumor regressions were observed in each patient. In three other patients with splenomegaly and/or large tumor burden, biodistribution studies indicated that '''(-labeled antibody could not deliver more radiation to tumor than to normal organs and these patients were not treated. Thus, tumor burden and spleen size may determine the feasibility of treatment with radiola beled antibody. Treatment with this antibody labeled with high doses of '"I was well tolerated and may prove therapeutical!}' useful. These studies are being continued to determine the maximal doses of radiation that can be tolerated by nonhematopoietic tissues after infusion of '"I-labeled