A phase I/II trial of iodine-131-tositumomab (anti-CD20), etoposide, cyclophosphamide, and autologous stem cell transplantation for relapsed B-cell lymphomas

Relapsed B-cell lymphomas are incurable with conventional chemotherapy and radiation therapy, although a fraction of patients can be cured with high-d ose chemoradiotherapy and autologous stem-cell transplantation (ASCT), We c onducted a phase I/II trial to estimate the maximum tolerated dose (MTD) of iodine 131 (I-131)-tositumomab (anti-CD20 antibody) that could be combined with etoposide and cyclophosphamide followed by ASCT in patients with rela psed B-cell lymphomas. Fifty-two patients received a trace-labeled infusion of 1.7 mg/kg I-131-tositumomab (185-370 MBq) followed by serial quantitati ve gamma-camera imaging and estimation of absorbed doses of radiation to tu mor sites and normal organs. Ten days later, patients received a therapeuti c infusion of 1.7 mg/kg tositumomab labeled with an amount of I-131 calcula ted to deliver the target dose of radiation (20-27 Gy) to critical normal o rgans (liver, kidneys, and lungs). Patients were maintained in radiation is olation until their total-body radioactivity was less than 0.07 mSv/h at 1 m, They were then given etoposide and cyclophosphamide followed by ASCT. Th e MTD of I-131-tositumomab that could be safely combined with 60 mg/kg etop oside and 100 mg/kg cyclophosphamide delivered 25 Gy to critical normal org ans. The estimated overall survival (OS) and progression-free survival (PFS ) of all treated patients at 2 years was 83% and 68%, respectively. These f indings compare favorably with those in a nonrandomized control group of pa tients who underwent transplantation, external-beam total-body irradiation, and etoposide and cyclophosphamide therapy during the same period (OS of 5 3% and PFS of 36% at 2 years), even after adjustment for confounding variab les in a multivariable analysis. (C) 2000 by The American Society of Hemato logy.