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Bortezomib therapy in patients with relapsed or refractory lymphoma: Potential correlation of in vitro sensitivity and tumor necrosis factor alpha response with clinical activity

Bortezomib therapy in patients with relapsed or refractory lymphoma: Potential correlation of in vitro sensitivity and tumor necrosis factor alpha response with clinical activity
Bortezomib therapy in patients with relapsed or refractory lymphoma: Potential correlation of in vitro sensitivity and tumor necrosis factor alpha response with clinical activity
To determine the efficacy of bortezomib in patients with lymphoid malignancy, correlating clinical response with effect on plasma cytokines and in vitro activity in primary cultures. Patients and Methods Patients received bortezomib (1.3 mg/m(2)) on days 1, 4, 8, and 11 of a 3-week cycle. Plasma tumor necrosis factor alpha (TNF-alpha) and interleukin-6 were measured before each treatment, and bortezomib activity was examined in patient samples grown in primary culture. Results Fifty-one patients received a total of 193 cycles of treatment. Twenty-four patients had mantle cell lymphoma (MCL), 13 had follicular lymphoma (FL), six had lymphoplasmacytic lymphoma, six had Hodgkin's disease (HD), and one each had diffuse large B-cell lymphoma and adult T-cell leukemia/lymphoma. Patients were heavily pretreated with a median of four previous therapies. Significant grade 3 to 4 toxicities were thrombocytopenia (n=22), fatigue (n=10), and peripheral neuropathy (n=3). Seven patients with MCL responded to treatment (one complete response, six partial responses [PRs]; overall response rate, 29%). Two patients with FL achieved a late PR 3 months after discontinuing therapy. Two patients with Waldenstrom's macroglobulinemia and one patient with HD achieved a PR. MCL primary cultures demonstrated greater sensitivity to bortezomib than FL (median 50% effective concentration for viability, 209 nmol/L v 1,311 nmol/L, respectively; P=.07), which correlated with clinical response. A median reduction in plasma TNF-alpha of 98% was observed in six patients with MCL who responded to bortezomib compared with a reduction of 38% in six nonresponders (P=.07). Conclusion Bortezomib demonstrates encouraging efficacy in MCL in heavily pretreated individuals. Response was associated with a reduction in plasma TNF-alpha and in vitro sensitivity in a small number of patients.
tumor-necrosis-factor, tumor, follicular lymphoma, non-hodgkins-lymphoma, cell, time, hematologic malignancies, international workshop, malignancy, lymphoma, necrosis, cultures, efficacy, treatment, phase-ii, b-cell lymphoma, multiple-myeloma cells, mantle cell lymphoma, cell lymphoma, cycle, therapy, disease, culture, individuals, apoptosis, t-cell, cycle arrest, large b-cell lymphoma, proteasome inhibitor ps-341, in-vitro, responses, cytokines, b cell, malignancies, patient
1527-7755
2105-2112
Strauss, S.J.
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Maharaj, L.
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Hoare, S.
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Johnson, P.W.
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Radford, J.A.
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Vinnecombe, S.
b24f1dbf-0204-4df7-9c2a-994fe9994f6a
Millard, L.
deeaea6c-70cb-4dc4-b817-16b12ce36c34
Rohatiner, A.
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Boral, A.
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Trehu, E.
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Schenkein, D.
22495ae6-3337-4923-851f-1168a4d8c74a
Balkwill, F.
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Joel, S.P.
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Lister, T.A.
ffe041c9-eb11-47e8-8c7c-177f8bc193c9
Strauss, S.J.
2a173c40-4617-465b-a550-b1ac7be45c55
Maharaj, L.
5f69f772-be78-4c8d-a5c7-50deefd9fffa
Hoare, S.
09276c31-606b-4d9c-99d3-b4cd0d822d38
Johnson, P.W.
3f6068ce-171e-4c2c-aca9-dc9b6a37413f
Radford, J.A.
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Vinnecombe, S.
b24f1dbf-0204-4df7-9c2a-994fe9994f6a
Millard, L.
deeaea6c-70cb-4dc4-b817-16b12ce36c34
Rohatiner, A.
9a45bee1-957c-4b7a-b686-8c7dd1ceb7a1
Boral, A.
9f620c9c-941e-406e-bc62-7722c253da4e
Trehu, E.
0d68a120-9021-4081-9703-599f68c4ae4e
Schenkein, D.
22495ae6-3337-4923-851f-1168a4d8c74a
Balkwill, F.
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Joel, S.P.
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Lister, T.A.
ffe041c9-eb11-47e8-8c7c-177f8bc193c9

Strauss, S.J., Maharaj, L., Hoare, S., Johnson, P.W., Radford, J.A., Vinnecombe, S., Millard, L., Rohatiner, A., Boral, A., Trehu, E., Schenkein, D., Balkwill, F., Joel, S.P. and Lister, T.A. (2006) Bortezomib therapy in patients with relapsed or refractory lymphoma: Potential correlation of in vitro sensitivity and tumor necrosis factor alpha response with clinical activity. Journal of Clinical Oncology, 24 (13), 2105-2112. (doi:10.1200/JCO.2005.04.6789).

Record type: Article

Abstract

To determine the efficacy of bortezomib in patients with lymphoid malignancy, correlating clinical response with effect on plasma cytokines and in vitro activity in primary cultures. Patients and Methods Patients received bortezomib (1.3 mg/m(2)) on days 1, 4, 8, and 11 of a 3-week cycle. Plasma tumor necrosis factor alpha (TNF-alpha) and interleukin-6 were measured before each treatment, and bortezomib activity was examined in patient samples grown in primary culture. Results Fifty-one patients received a total of 193 cycles of treatment. Twenty-four patients had mantle cell lymphoma (MCL), 13 had follicular lymphoma (FL), six had lymphoplasmacytic lymphoma, six had Hodgkin's disease (HD), and one each had diffuse large B-cell lymphoma and adult T-cell leukemia/lymphoma. Patients were heavily pretreated with a median of four previous therapies. Significant grade 3 to 4 toxicities were thrombocytopenia (n=22), fatigue (n=10), and peripheral neuropathy (n=3). Seven patients with MCL responded to treatment (one complete response, six partial responses [PRs]; overall response rate, 29%). Two patients with FL achieved a late PR 3 months after discontinuing therapy. Two patients with Waldenstrom's macroglobulinemia and one patient with HD achieved a PR. MCL primary cultures demonstrated greater sensitivity to bortezomib than FL (median 50% effective concentration for viability, 209 nmol/L v 1,311 nmol/L, respectively; P=.07), which correlated with clinical response. A median reduction in plasma TNF-alpha of 98% was observed in six patients with MCL who responded to bortezomib compared with a reduction of 38% in six nonresponders (P=.07). Conclusion Bortezomib demonstrates encouraging efficacy in MCL in heavily pretreated individuals. Response was associated with a reduction in plasma TNF-alpha and in vitro sensitivity in a small number of patients.

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Published date: 2006
Keywords: tumor-necrosis-factor, tumor, follicular lymphoma, non-hodgkins-lymphoma, cell, time, hematologic malignancies, international workshop, malignancy, lymphoma, necrosis, cultures, efficacy, treatment, phase-ii, b-cell lymphoma, multiple-myeloma cells, mantle cell lymphoma, cell lymphoma, cycle, therapy, disease, culture, individuals, apoptosis, t-cell, cycle arrest, large b-cell lymphoma, proteasome inhibitor ps-341, in-vitro, responses, cytokines, b cell, malignancies, patient

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Local EPrints ID: 62934
URI: http://eprints.soton.ac.uk/id/eprint/62934
ISSN: 1527-7755
PURE UUID: 6beb6673-ffe1-44af-b906-eaa35b768559
ORCID for P.W. Johnson: ORCID iD orcid.org/0000-0003-2306-4974

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Date deposited: 05 Sep 2008
Last modified: 03 Dec 2019 01:57

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Contributors

Author: S.J. Strauss
Author: L. Maharaj
Author: S. Hoare
Author: P.W. Johnson ORCID iD
Author: J.A. Radford
Author: S. Vinnecombe
Author: L. Millard
Author: A. Rohatiner
Author: A. Boral
Author: E. Trehu
Author: D. Schenkein
Author: F. Balkwill
Author: S.P. Joel
Author: T.A. Lister

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