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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
Abstract
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 (131)I 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 (131)I tositumomab can, therefore, produce frequent and durable responses in NHL, especially low-grade or transformed NHL. (Blood. 2000;96:1259-1266)
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“and in patients receiving 131 I-tositumomab (MTD 5 75 cGy, single administration in heavily pretreated patients without major marrow involvement with tumor) ( 92 , 93 ).”
From Normal-Tissue Tolerance to Radiopharmaceutical Therapies, the Knowns and the Unknowns (2021) · cites this paper as [93]
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Metadata
- Authors
- Kaminski, M. S., Estes, J., Zasadny, K. R., Francis, I. R., Ross, C. W., Tuck, M., Regan, D., Fisher, S., Gutierrez, J., Kroll, S., Stagg, R., Tidmarsh, G., & Wahl, R. L.
- Affiliations
- University of Michigan (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2000-08-15
- Volume
- 96
- Issue
- 4
- Pages
- 1259-1266
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1573890015
- Cited by
- 525
- References
- 56
- Citations by year
- 2025: 1 · 2024: 9 · 2023: 7 · 2022: 7 · 2021: 4 · 2020: 13 · 2019: 7 · 2018: 7 · 2017: 11 · 2016: 15 · 2015: 14 · 2014: 17 · 2013: 14 · 2012: 21
- FWCI
- 41.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ca056794-08)
- National Cancer Institute (R01-CA-56794, P01-CA-42678)
- National Center for Research Resources (M-01RR00042, M01RR000042)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
- Keywords
- radioimmunotherapy, iodine-131 tositumomab, B-cell non-Hodgkin lymphoma, relapsed/refractory lymphoma, autologous stem cell transplantation, progression-free survival, complete response, long-term follow-up, hematologic toxicity, human anti-mouse antibodies, thyroid-stimulating hormone, myelodysplastic syndrome
- MeSH terms
- Adult, Aged, Antibodies, Monoclonal, Female, Follow-Up Studies, Humans, Iodine Radioisotopes, Male, Middle Aged, Recurrence, Lymphoma, B-Cell, Radioimmunotherapy, Treatment Outcome, Antigens, CD20
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