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

Abstract.

Dosimetry studies in patients with non-Hodgkin’s lymphoma were performed to estimate the radiation absorbed dose to normal organs and bone marrow from 90Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) treatment in this phase I/II, multicenter trial. The trial was designed to determine the dose of Rituximab (chimeric anti-CD20, Rituxan, IDEC-C2B8, MabThera), the unlabeled antibody given prior to the radioconjugate to clear peripheral blood B cells and optimize distribution, and to determine the maximum tolerated dose of 90Y-Zevalin [7.4, 11, or 15 MBq/kg (0.2, 0.3, or 0.4 mCi/kg)]. Patients received 111In-Zevalin (indium-111 ibritumomab tiuxetan, IDEC-In2B8 ) on day 0 followed by a therapeutic dose of 90Y-Zevalin on day 7. Both doses were preceded by an infusion of the chimeric, unlabeled antibody Rituximab. Following administration of 111In-Zevalin, serial anterior/posterior whole-body scans were acquired. Major-organ radioactivity versus time estimates were calculated using regions of interest. Residence times were computed and entered into the MIRDOSE3 computer software program to calculate estimated radiation absorbed dose to each organ. Initial analyses of estimated radiation absorbed dose were completed at the clinical site. An additional, centralized dosimetry analysis was performed subsequently to provide a consistent analysis of data collected from the seven clinical sites. In all patients with dosimetry data (n =56), normal organ and red marrow radiation absorbed doses were estimated to be well under the protocol-defined upper limit 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 0.72–4.4 Gy), and 0.38 Gy to kidneys (range 0.07–0.61 Gy). Median estimated tumor radiation absorbed dose was 17 Gy (range 5.8–67 Gy). No correlation was noted between hematologic toxicity and the following variables: red marrow radiation absorbed dose, blood T 1/2, blood AUC, plasma T 1/2, and plasma AUC. It is concluded that 90Y-Zevalin administered at nonmyeloablative maximum tolerated doses results in acceptable radiation absorbed doses to normal organs. The only toxicity of note is hematologic and is not correlated to red marrow radiation absorbed dose estimates or T 1/2, reflecting that hematologic toxicity is dependent on bone marrow reserve in this heavily pretreated population.

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Authors and Affiliations

1. Department of Radiology, Nuclear Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minn., USA, , , , , , US
   Gregory A. Wiseman, Michael Stabin & William L. Dunn
2. Department of Internal Medicine Division of Hematology, Mayo Clinic and Mayo Foundation, Rochester, Minn., USA, , , , , , US
   Thomas E. Witzig
3. IDEC Pharmaceuticals Corp., San Diego, Calif., USA, , , , , , US
   Christine A. White, Judy R. Berlfein, Eric Ding & Antonio J. Grillo-López
4. Division of Hematology/Oncology, Department of Medicine, Northwestern University and Robert H. Lurie Comprehensive Cancer Center, Chicago, Ill., USA, , , , , , US
   William Erwin & Stewart Spies
5. University of California at Los Angeles, Los Angeles, Calif., USA, , , , , , US
   Magnus Dahlbom & Daniel H. S. Silverman
6. City of Hope, Duarte, Calif., USA, , , , , , US
   Andrew Raubitschek
7. Henry Ford Hospital, Detroit, Mich., USA, , , , , , US
   Kastytis Karvelis
8. Ryan Belanger Associates, San Diego, Calif., USA, , , , , , US
   Richard Belanger
9. Fox Chase Cancer Center, Philadelphia, Pa., USA, , , , , , US
   Timothy Schultheiss

Authors

1. Gregory A. Wiseman
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2. Christine A. White
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3. Michael Stabin
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4. William L. Dunn
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5. William Erwin
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6. Magnus Dahlbom
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7. Andrew Raubitschek
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8. Kastytis Karvelis
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9. Timothy Schultheiss
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10. Thomas E. Witzig
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11. Richard Belanger
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12. Stewart Spies
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13. Daniel H. S. Silverman
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14. Judy R. Berlfein
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15. Eric Ding
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16. Antonio J. Grillo-López
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Received 24 January and in revised form 20 March 2000

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Wiseman, G., White, C., Stabin, M. et al. Phase I/II 90Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) radioimmunotherapy dosimetry results in relapsed or refractory non-Hodgkin’s lymphoma.Eur J Nucl Med 27, 766–777 (2000). https://doi.org/10.1007/s002590000276

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• Issue Date: June 2000
• DOI: https://doi.org/10.1007/s002590000276