Phase I/II Y-90-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) radioimmunotherapy dosimetry results in relapsed or refractory non-Hodgkin's lymphoma

Dosimetry studies in patients with non-Hodgkin's lymphoma were performed to estimate the radiation absorbed dose to normal organs and bone marrow from Y-90-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) treatment in thi s phase I/II, multicenter trial. The trial was designed to determine the do se of Rituximab (chimeric anti-CD20, Rituxan, IDEC-C2B8, MabThera), the unl abeled antibody given prior to the radioconjugate to clear peripheral blood B cells and optimize distribution, and to determine the maximum tolerated dose of Y-90-Zevalin [7.4, 11, or 15 MBq/kg (0.2, 0.3, or 0.4 mCi/kg)], Pat ients received In-111-Zevalin (indium-111 ibritumomab tiuxetan, IDEC-In2B8) on day 0 followed by a therapeutic dose of Y-90-Zevalin on day 7. Both dos es were preceded by an infusion of the chimeric, unlabeled antibody Rituxim ab. Following administration of 111In-Zevalin, serial anterior/posterior wh ole body scans were acquired. Major-organ radioactivity versus time estimat es were calculated using regions of interest. Residence times were computed and entered into the MIRDOSE3 computer software program to calculate estim ated radiation absorbed dose to each organ. Initial analyses of estimated r adiation absorbed dose were completed at the clinical site. An additional, centralized dosimetry analysis was performed subsequently to provide a cons istent analysis of data collected from the seven clinical sites. In all pat ients with dosimetry data (n=56), normal organ and red marrow radiation abs orbed doses were estimated to be well under the protocol-defined upper limi t of 20 Gy and 3 Gy, respectively. Median estimated radiation absorbed dose was 3.4 Gy to liver (range 1.2-7.8 Gy), 2.6 Gy to lungs (range 0.723.4 Gy) , and 0.38 Gy to kidneys (range 0.07-0.61 Gy). Median estimated tumor radia tion absorbed dose was 17 Gy (range 5.8-67 Gy). No correlation was noted be tween hematologic toxicity and the following variables: red marrow radiatio n absorbed dose, blood T-1/2, blood AUC, plasma T-1/2, and plasma AUC. It i s concluded that Y-90-Zevalin administered at nonmyeloablative maximum tole rated doses results in acceptable radiation absorbed doses to normal organs . The only toxicity of note is hematologic and is not correlated to red mar row radiation absorbed dose estimates or T-1/2, reflecting that hematologic toxicity is dependent on bone marrow reserve in this heavily pretreated po pulation.