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Iodine-131-anti-B1 radioimmunotherapy for B-cell lymphoma
Abstract
PURPOSE: The CD20 B-lymphocyte surface antigen expressed by B-cell lymphomas is an attractive target for radioimmunotherapy, treatment using radiolabeled antibodies. We conducted a phase I dose-escalation trial to assess the toxicity, tumor targeting, and efficacy of nonmyeloablative doses of an anti-CD20 monoclonal antibody (anti-B1) labeled with iodine-131 (131I) in 34 patients with B-cell lymphoma who had failed chemotherapy. PATIENTS AND METHODS: Patients were first given tracelabeled doses of 131I-labeled anti-B1 (15 to 20 mg, 5 mCi) to assess radiolabeled antibody biodistribution, and then a radioimmunotherapeutic dose (15 to 20 mg) labeled with a quantity of 131I that would deliver a specified centigray dose of whole-body radiation predicted by the tracer dose. Whole-body radiation doses were escalated from 25 to 85 cGy in sequential groups of patients in 10-cGy increments. To evaluate if radiolabeled antibody biodistribution could be optimized, initial patients were given one or two additional tracer doses on successive weeks, each dose preceded by an infusion of 135 mg of unlabeled anti-B1 one week and 685 mg the next. The unlabeled antibody dose resulting in the most optimal tracer biodistribution was also given before the radioimmunotherapeutic dose. Later patients were given a single tracer dose and radioimmunotherapeutic dose preceded by infusion of 685 mg of unlabeled anti-B1. RESULTS: Treatment was well tolerated. Hematologic toxicity was dose-limiting, and 75 cGy was established as the maximally tolerated whole-body radiation dose. Twenty-eight patients received radioimmunotherapeutic doses of 34 to 161 mCi, resulting in complete remission in 14 patients and a partial response in eight. All 13 patients with low-grade lymphoma responded, and 10 achieved a complete remission. Six of eight patients with transformed lymphoma responded. Thirteen of 19 patients whose disease was resistant to their last course of chemotherapy and all patients with chemotherapy-sensitive disease responded. The median duration of complete remission exceeds 16.5 months. Six patients remain in complete remission 16 to 31 months after treatment. CONCLUSION: Nonmyeloablative radioimmunotherapy with 131I-anti-B1 is associated with a high rate of durable remissions in patients with B-cell lymphoma refractory to chemotherapy.
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“The clinical trials leading to the approval of anti-CD20 radioimmunotherapies intentionally excluded patients with bone marrow involvement with tumor of . 25% ( 92 ).”
From Normal-Tissue Tolerance to Radiopharmaceutical Therapies, the Knowns and the Unknowns (2021) · cites this paper as [92]
In the citing paper
“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 [92]
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Metadata
- Authors
- Kaminski, M. S., Zasadny, K. R., Francis, I. R., Fenner, M. C., Ross, C. W., Milik, A. W., Estes, J., Tuck, M., Regan, D., Fisher, S., Glenn, S. D., & Wahl, R. L.
- Affiliations
- University of Michigan (US)
- Venue
- Journal of Clinical Oncology
- Published
- 1996-07
- Volume
- 14
- Issue
- 7
- Pages
- 1974-1981
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W1892026381
- Cited by
- 396
- References
- 0
- Citations by year
- 2024: 2 · 2023: 6 · 2022: 5 · 2021: 3 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 4 · 2016: 5 · 2015: 4 · 2014: 5 · 2013: 4 · 2012: 6
- FWCI
- 28.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ca056794-08, 5p01ca042768-03)
- National Cancer Institute (R01-CA-56794, P0-1 CA42768)
- 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
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Keywords
- iodine-131, anti-CD20 monoclonal antibody, radioimmunotherapy, B-cell lymphoma, treatment toxicity, hematologic toxicity, tumor targeting, tissue distribution, complete remission, relapsed/refractory lymphoma, indolent lymphoma, transformed lymphoma, chemotherapy-refractory disease
- MeSH terms
- Adult, Aged, Antibodies, Monoclonal, Dose-Response Relationship, Radiation, Female, Humans, Iodine Radioisotopes, Male, Middle Aged, Remission Induction, Lymphoma, B-Cell, Radioimmunotherapy, Antigens, CD20
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