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Blood, 15 August 2000, Vol. 96, No. 4, pp. 1259-1266
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Radioimmunotherapy with iodine 131I tositumomab for
relapsed or refractory B-cell non-Hodgkin lymphoma: updated results and
long-term follow-up of the University of Michigan
experience
Mark S. Kaminski,
Judith Estes,
Kenneth R. Zasadny,
Isaac R. Francis,
Charles W. Ross,
Melissa Tuck,
Denise Regan,
Susan Fisher,
Jeanne Gutierrez,
Stewart Kroll,
Robert Stagg,
George Tidmarsh, and
Richard L. Wahl
From the Divisions of Hematology/Oncology and
Nuclear Medicine, Departments of Internal Medicine, Radiology and
Pathology, University of Michigan, Ann Arbor, MI; and Coulter
Pharmaceutical, Inc, South San Francisco, CA.
CD20-targeted radioimmunotherapy is a promising new treatment for
B-cell non-Hodgkin lymphoma (NHL). We now provide updated and long-term
data on 59 chemotherapy-relapsed/refractory patients treated with
iodine 131I tositumomab in a phase I/II single-center
study. Fifty-three patients received individualized therapeutic doses,
delivering a specified total-body radiation dose (TBD) based on the
clearance rate of a preceding dosimetric dose. Six patients received
dosimetric doses only. Dose-escalations of TBD were conducted
separately in patients who had or had not undergone a prior autologous
stem cell transplant (ASCT) until a nonmyeloablative maximally
tolerated TBD was established (non-ASCT = 75 cGy, post-ASCT = 45
cGy). Fourteen additional non-ASCT patients were treated with 75 cGy.
Unlabeled antibody was given prior to labeled dosimetric and
therapeutic doses to improve biodistribution. Forty-two (71%) of 59 patients responded; 20 (34%) had complete responses (CR). Thirty-five
(83%) of 42 with low-grade or transformed NHL responded versus 7 (41%) of 17 with de novo intermediate-grade NHL
(P = .005). For all 42 responders, the median
progression-free survival was 12 months, 20.3 for those with CR. Seven
patients remain in CR 3 to 5.7 years. Sixteen patients were re-treated
after progression; 9 responded and 5 had a CR. Reversible hematologic
toxicity was dose limiting. Only 10 patients (17%) had human
anti-mouse antibodies detected. Long-term, 5 patients developed
elevated thyroid-stimulating hormone levels, 5 were diagnosed with
myelodysplasia and 3 with solid tumors. A single, well-tolerated
treatment with iodine 131I tositumomab can, therefore,
produce frequent and durable responses in NHL, especially low-grade or
transformed NHL.

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J. M. Pagel, N. Hedin, K. Subbiah, D. Meyer, R. Mallet, D. Axworthy, L. J. Theodore, D. S. Wilbur, D. C. Matthews, and O. W. Press
Comparison of anti-CD20 and anti-CD45 antibodies for conventional and pretargeted radioimmunotherapy of B-cell lymphomas
Blood,
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[Abstract]
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T. A. Riccobene, R. C. Miceli, C. Lincoln, Y. Knight, J. Meadows, M. G. Stabin, and C. Sung
Rapid and Specific Targeting of 125I-Labeled B Lymphocyte Stimulator to Lymphoid Tissues and B Cell Tumors in Mice
J. Nucl. Med.,
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[Abstract]
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D. J. Buchsbaum and A. F. LoBuglio
Targeting of 125I-Labeled B Lymphocyte Stimulator
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K. Subbiah, D. K. Hamlin, J. M. Pagel, D. S. Wilbur, D. L. Meyer, D. B. Axworthy, R. W. Mallett, L. J. Theodore, P. S. Stayton, and O. W. Press
Comparison of Immunoscintigraphy, Efficacy, and Toxicity of Conventional and Pretargeted Radioimmunotherapy in CD20-Expressing Human Lymphoma Xenografts
J. Nucl. Med.,
March 1, 2003;
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J. O. Armitage, P. P. Carbone, J. M. Connors, A. Levine, J. M. Bennett, and S. Kroll
Treatment-Related Myelodysplasia and Acute Leukemia in Non-Hodgkin's Lymphoma Patients
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March 1, 2003;
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G. Sgouros, S. Squeri, A. M. Ballangrud, K. S. Kolbert, J. B. Teitcher, K. S. Panageas, R. D. Finn, C. R. Divgi, S. M. Larson, and A. D. Zelenetz
Patient-Specific, 3-Dimensional Dosimetry in Non-Hodgkin's Lymphoma Patients Treated with 131I-anti-B1 Antibody: Assessment of Tumor Dose-Response
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M. S. Cragg, S. M. Morgan, H. T. C. Chan, B. P. Morgan, A. V. Filatov, P. W. M. Johnson, R. R. French, and M. J. Glennie
Complement-mediated lysis by anti-CD20 mAb correlates with segregation into lipid rafts
Blood,
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[Abstract]
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G. L. Griffiths, S. V. Govindan, R. M. Sharkey, D. R. Fisher, and D. M. Goldenberg
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M. E. Juweid
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D. R. Colnot, G. J. Ossenkoppele, J. C. Roos, J. J. Quak, R. de Bree, P. K. Borjesson, P. C. Huijgens, G. B. Snow, and G. A. M. S. van Dongen
Reinfusion of Unprocessed, Granulocyte Colony-stimulating Factor-stimulated Whole Blood Allows Dose Escalation of 186Relabeled Chimeric Monoclonal Antibody U36 Radioimmunotherapy in a Phase I Dose Escalation Study
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D. W. Seldin
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R. O. Dillman
Radiolabeled Anti-CD20 Monoclonal Antibodies for the Treatment of B-Cell Lymphoma
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M. Hunault-Berger, N. Ifrah, and P. Solal-Celigny
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J. G. Jurcic, S. M. Larson, G. Sgouros, M. R. McDevitt, R. D. Finn, C. R. Divgi, A. M. Ballangrud, K. A. Hamacher, D. Ma, J. L. Humm, et al.
Targeted alpha particle immunotherapy for myeloid leukemia
Blood,
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P. McLaughlin
Progress and Promise in the Treatment of Indolent Lymphomas
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G. A. Wiseman, L. I. Gordon, P. S. Multani, T. E. Witzig, S. Spies, N. L. Bartlett, R. J. Schilder, J. L. Murray, M. Saleh, R. S. Allen, et al.
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T. E. Witzig, L. I. Gordon, F. Cabanillas, M. S. Czuczman, C. Emmanouilides, R. Joyce, B. L. Pohlman, N. L. Bartlett, G. A. Wiseman, N. Padre, et al.
Randomized Controlled Trial of Yttrium-90-Labeled Ibritumomab Tiuxetan Radioimmunotherapy Versus Rituximab Immunotherapy for Patients With Relapsed or Refractory Low-Grade, Follicular, or Transformed B-Cell Non-Hodgkin's Lymphoma
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D. M. Goldenberg
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J. A. Siegel, S. Kroll, D. Regan, M. S. Kaminski, and R. L. Wahl
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H. Kobayashi, K. Shirakawa, S. Kawamoto, T. Saga, N. Sato, A. Hiraga, I. Watanabe, Y. Heike, K. Togashi, J. Konishi, et al.
Rapid Accumulation and Internalization of Radiolabeled Herceptin in an Inflammatory Breast Cancer Xenograft with Vasculogenic Mimicry Predicted by the Contrast-enhanced Dynamic MRI with the Macromolecular Contrast Agent G6-(1B4M-Gd)256
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J. M. Vose, B. C.-H. Chiu, B. D. Cheson, J. Dancey, and J. Wright
Update on Epidemiology and Therapeutics for Non-Hodgkin's Lymphoma
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O. W. Press, M. Corcoran, K. Subbiah, D. K. Hamlin, D. S. Wilbur, T. Johnson, L. Theodore, E. Yau, R. Mallett, D. L. Meyer, et al.
A comparative evaluation of conventional and pretargeted radioimmunotherapy of CD20-expressing lymphoma xenografts
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B. D. Cheson
Some Like It Hot!
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M. S. Kaminski, A. D. Zelenetz, O. W. Press, M. Saleh, J. Leonard, L. Fehrenbacher, T. A. Lister, R. J. Stagg, G. F. Tidmarsh, S. Kroll, et al.
Pivotal Study of Iodine I 131 Tositumomab for Chemotherapy-Refractory Low-Grade or Transformed Low-Grade B-Cell Non-Hodgkin's Lymphomas
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S. L. McCune, J. P. Gockerman, and D. A. Rizzieri
Monoclonal Antibody Therapy in the Treatment of Non-Hodgkin Lymphoma
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O. W. Press, J. P. Leonard, B. Coiffier, R. Levy, and J. Timmerman
Immunotherapy of Non-Hodgkin's Lymphomas
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