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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

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
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
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.
chemotherapy, therapy, monoclonal antibody, monoclonal-antibodies, cyclophosphamide, combination, cell, expression, patient, non-hodgkins-lymphoma, lymphoma, leukemia, monoclonal-antibody, low-grade, trial, cd20, time, lymphocytic-leukemia, chronic lymphocytic-leukemia, efficacy, rituximab, maintenance therapy, b cell, cells, mitoxantrone, response duration, molecules
0006-4971
5486-5495
Hagenbeek, A.
d7b8edbe-9308-40b5-932a-5339d7450336
Gadeberg, O.
ecbb62ce-a654-45c3-b4fa-e3c539545628
Johnson, P.
3f6068ce-171e-4c2c-aca9-dc9b6a37413f
Pedersen, L.M.
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Walewski, J.
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Hellmann, A.
4e6d2a62-489b-4a8b-8ead-1973110870f0
Link, B.K.
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Robak, T.
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Wojtukiewicz, M.
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Pfreundschuh, M.
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Kneba, M.
cbb2fede-32e5-4efa-b944-82b13d2cb9a8
Engert, A.
eab2712c-2927-481d-ac5c-b2a579256ce2
Sonneveld, P.
b2fc5ffb-e8da-450e-a318-fbc1a0d9c894
Flensburg, M.
a6340cae-0bc9-4634-85bc-24d8b6bfebfb
Petersen, J.
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Losic, N.
b6831420-0d0f-4bec-870f-ab283edbc748
Radford, J.
1a8a0bd5-8ef3-46af-b35c-3a4bba491eee
Hagenbeek, A.
d7b8edbe-9308-40b5-932a-5339d7450336
Gadeberg, O.
ecbb62ce-a654-45c3-b4fa-e3c539545628
Johnson, P.
3f6068ce-171e-4c2c-aca9-dc9b6a37413f
Pedersen, L.M.
a0ad69aa-c888-487f-a302-44746a8a4939
Walewski, J.
484ad2fa-a169-4a32-892c-894d50eda025
Hellmann, A.
4e6d2a62-489b-4a8b-8ead-1973110870f0
Link, B.K.
e3998c09-76b2-4800-96e3-0c900e4b90cd
Robak, T.
324e6a9d-cee7-48c5-93fc-8aa61fd68476
Wojtukiewicz, M.
1ca41cf5-4d6a-475d-8a73-7985e22842b2
Pfreundschuh, M.
ae57a75a-e89e-46dd-8d49-f3a084c3b64e
Kneba, M.
cbb2fede-32e5-4efa-b944-82b13d2cb9a8
Engert, A.
eab2712c-2927-481d-ac5c-b2a579256ce2
Sonneveld, P.
b2fc5ffb-e8da-450e-a318-fbc1a0d9c894
Flensburg, M.
a6340cae-0bc9-4634-85bc-24d8b6bfebfb
Petersen, J.
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Losic, N.
b6831420-0d0f-4bec-870f-ab283edbc748
Radford, J.
1a8a0bd5-8ef3-46af-b35c-3a4bba491eee

Hagenbeek, A., Gadeberg, O., 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. and 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, 111 (12), 5486-5495. (doi:10.1182/blood-2007-10-117671).

Record type: Article

Abstract

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.

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More information

Published date: 2008
Keywords: chemotherapy, therapy, monoclonal antibody, monoclonal-antibodies, cyclophosphamide, combination, cell, expression, patient, non-hodgkins-lymphoma, lymphoma, leukemia, monoclonal-antibody, low-grade, trial, cd20, time, lymphocytic-leukemia, chronic lymphocytic-leukemia, efficacy, rituximab, maintenance therapy, b cell, cells, mitoxantrone, response duration, molecules

Identifiers

Local EPrints ID: 62763
URI: http://eprints.soton.ac.uk/id/eprint/62763
ISSN: 0006-4971
PURE UUID: 4ca6ddd2-e5dd-4ab3-88f9-b87380ef7583
ORCID for P. Johnson: ORCID iD orcid.org/0000-0003-2306-4974

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Date deposited: 02 Sep 2008
Last modified: 16 Mar 2024 02:59

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Contributors

Author: A. Hagenbeek
Author: O. Gadeberg
Author: P. Johnson ORCID iD
Author: L.M. Pedersen
Author: J. Walewski
Author: A. Hellmann
Author: B.K. Link
Author: T. Robak
Author: M. Wojtukiewicz
Author: M. Pfreundschuh
Author: M. Kneba
Author: A. Engert
Author: P. Sonneveld
Author: M. Flensburg
Author: J. Petersen
Author: N. Losic
Author: J. Radford

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