First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial
| Autor: | Brian K. Link, Pieter Sonneveld, Michael Kneba, Marek Z. Wojtukiewicz, Ole V. Gadeberg, Peter Johnson, John Radford, Jørgen Petersen, Michael Pfreundschuh, Nedjad Losic, Andreas Engert, Anton Hagenbeek, Lars Møller Pedersen, Tadeusz Robak, Jan Walewski, Mimi Flensburg, Andrzej Hellmann |
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| Přispěvatelé: | Cancer Center Amsterdam, Clinical Haematology, Hematology, Cardiology |
| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Oncology medicine.medical_specialty Chronic lymphocytic leukemia Immunology Follicular lymphoma Kaplan-Meier Estimate Antibodies Monoclonal Humanized Infections Ofatumumab Biochemistry chemistry.chemical_compound Recurrence Internal medicine medicine Humans Lymphoma Follicular Aged CD20 B-Lymphocytes Hematology Dose-Response Relationship Drug biology business.industry Antibodies Monoclonal Cell Biology Middle Aged Antigens CD20 medicine.disease Lymphoma Treatment Outcome chemistry Drug Resistance Neoplasm Monoclonal biology.protein Female Refractory Follicular Lymphoma business Follow-Up Studies |
| Zdroj: | Hagenbeek, A, Gadeberg, O V, Johnson, P, Pedersen, L M, Walewski, J, Hellmann, A, Link, B K, Robak, T, Wojtukiewicz, M, Pfreundschuh, M, Kneba, M, Engert, A, Sonneveld, P, Flensburg, M, Petersen, J, Losic, N & Radford, J 2008, ' First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma : results of a phase 1/2 trial ', Blood, vol. 111, no. 12, pp. 5486-5495 . https://doi.org/10.1182/blood-2007-10-117671 Blood, 111(12), 5486-5495. American Society of Hematology |
| ISSN: | 0006-4971 0009-2274 |
| Popis: | Ofatumumab is a unique monoclonal antibody that targets a distinct small loop epitope on the CD20 molecule. Preclinical data show that ofatumumab is active against B-cell lymphoma/chronic lymphocytic leukemia cells with low CD20-antigen density and high expression of complement inhibitory molecules. In a phase 1/2 trial evaluating safety and efficacy of ofatumumab in relapsed or refractory follicular non-Hodgkin lymphoma (FL) grade 1 or 2, 4 dose groups of 10 patients received 4 weekly infusions of 300, 500, 700, or 1000 mg. Patients had a median of 2 prior FL therapies and 13% had elevated lactate dehydrogenase. No safety concerns or maximum tolerated dose was identified. A total of 274 adverse events were reported; 190 were judged related to ofatumumab, most occurring on the first infusion day with Common Terminology Criteria grade 1 or 2. Eight related events were grade 3. Treatment caused immediate and profound B-cell depletion, and 65% of patients reverted to negative BCL2 status. Clinical response rates ranged from 20% to 63%. Median time to progression for all patients/responders was 8.8/32.6 months, and median duration of response was 29.9 months at a median/maximum follow-up of 9.2/38.6 months. Ofatumumab is currently being evaluated in patients with rituximab-refractory FL. This trial was registered at www.clinicaltrials.gov as #NCT00092274. |
| Databáze: | OpenAIRE |
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