Time to treatment response in patients with follicular lymphoma treated with bortezomib is longer compared with other histologic subtypes

Owen A. O'Connor, Carol Portlock, Craig Moskowitz, Paul Hamlin, David Straus, John Gerecitano, Mithat Gonen, Otilia Dumitrescu, Debra Sarasohn, John Butos, Ellen Neylon, Barbara Mac Gregor Cortelli, Susan Blumel, Andrew M. Evens, Andrew D. Zelenetz, John Wright, Brenda Cooper, Jane Winter, Julie Marie Vose

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Abstract

Purpose: To determine the antitumor activity of the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma. Experimental Design: Patients with follicular lymphoma (FL), marginal zone lymphoma, mantle cell lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, and Waldenstrom's macroglobulinemia were eligible for study. Bortezomib was given at a dose of 1.5 mg/m2 as an i.v. push on days 1, 4, 8, and 11 of a 21-day cycle. Eligibility included the following: (a) no more than three prior therapies, (b) at least 1 month since prior chemotherapy, (c) measurable disease, and (d) an absolute neutrophil count of >1,000/μL and a platelet count >50,000/μL for the first dose of any cycle. Results: Seventy-seven patients were registered, of which 69 were assessable for response based on the completion of two cycles of therapy. Subtypes included FL (59.5%), mantle cell lymphoma (52%), small lymphocytic lymphoma/chronic lymphocytic leukemia (16.2%), marginal zone lymphoma (21.6%), and one Waldenstrom's macroglobulinemia. The median number of prior therapies was three. Themost common grade 3 toxicity was lymphopenia (35%) and thrombocytopenia (31%). Twenty-five patients experienced grade ≤2 sensory neuropathy (32), and 8% experienced grade 3 neurosensory toxicity. The overall response rate was 45% (40% on an intention to treat) including 10 complete remissions. Of 18 patients with FL, 9 responded with 4 complete response. The median time to treatment response for FL was 12 weeks, whereas the median time to treatment response for other subtypes of non-Hodgkin's lymphoma was only 4 weeks. Conclusions: These data suggest that bortezomib has significant single agent activity in patients with FL, and that longer durations of treatment may improve overall response.

Original languageEnglish (US)
Pages (from-to)719-726
Number of pages8
JournalClinical Cancer Research
Volume16
Issue number2
DOIs
StatePublished - Jan 15 2010

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Follicular Lymphoma
B-Cell Chronic Lymphocytic Leukemia
Mantle-Cell Lymphoma
Waldenstrom Macroglobulinemia
Non-Hodgkin's Lymphoma
Therapeutics
Lymphopenia
Proteasome Inhibitors
Platelet Count
Thrombocytopenia
Bortezomib
Lymphoma
Neutrophils
Research Design
Drug Therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Time to treatment response in patients with follicular lymphoma treated with bortezomib is longer compared with other histologic subtypes. / O'Connor, Owen A.; Portlock, Carol; Moskowitz, Craig; Hamlin, Paul; Straus, David; Gerecitano, John; Gonen, Mithat; Dumitrescu, Otilia; Sarasohn, Debra; Butos, John; Neylon, Ellen; Cortelli, Barbara Mac Gregor; Blumel, Susan; Evens, Andrew M.; Zelenetz, Andrew D.; Wright, John; Cooper, Brenda; Winter, Jane; Vose, Julie Marie.

In: Clinical Cancer Research, Vol. 16, No. 2, 15.01.2010, p. 719-726.

Research output: Contribution to journalArticle

O'Connor, OA, Portlock, C, Moskowitz, C, Hamlin, P, Straus, D, Gerecitano, J, Gonen, M, Dumitrescu, O, Sarasohn, D, Butos, J, Neylon, E, Cortelli, BMG, Blumel, S, Evens, AM, Zelenetz, AD, Wright, J, Cooper, B, Winter, J & Vose, JM 2010, 'Time to treatment response in patients with follicular lymphoma treated with bortezomib is longer compared with other histologic subtypes', Clinical Cancer Research, vol. 16, no. 2, pp. 719-726. https://doi.org/10.1158/1078-0432.CCR-08-2647
O'Connor, Owen A. ; Portlock, Carol ; Moskowitz, Craig ; Hamlin, Paul ; Straus, David ; Gerecitano, John ; Gonen, Mithat ; Dumitrescu, Otilia ; Sarasohn, Debra ; Butos, John ; Neylon, Ellen ; Cortelli, Barbara Mac Gregor ; Blumel, Susan ; Evens, Andrew M. ; Zelenetz, Andrew D. ; Wright, John ; Cooper, Brenda ; Winter, Jane ; Vose, Julie Marie. / Time to treatment response in patients with follicular lymphoma treated with bortezomib is longer compared with other histologic subtypes. In: Clinical Cancer Research. 2010 ; Vol. 16, No. 2. pp. 719-726.
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abstract = "Purpose: To determine the antitumor activity of the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma. Experimental Design: Patients with follicular lymphoma (FL), marginal zone lymphoma, mantle cell lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, and Waldenstrom's macroglobulinemia were eligible for study. Bortezomib was given at a dose of 1.5 mg/m2 as an i.v. push on days 1, 4, 8, and 11 of a 21-day cycle. Eligibility included the following: (a) no more than three prior therapies, (b) at least 1 month since prior chemotherapy, (c) measurable disease, and (d) an absolute neutrophil count of >1,000/μL and a platelet count >50,000/μL for the first dose of any cycle. Results: Seventy-seven patients were registered, of which 69 were assessable for response based on the completion of two cycles of therapy. Subtypes included FL (59.5{\%}), mantle cell lymphoma (52{\%}), small lymphocytic lymphoma/chronic lymphocytic leukemia (16.2{\%}), marginal zone lymphoma (21.6{\%}), and one Waldenstrom's macroglobulinemia. The median number of prior therapies was three. Themost common grade 3 toxicity was lymphopenia (35{\%}) and thrombocytopenia (31{\%}). Twenty-five patients experienced grade ≤2 sensory neuropathy (32), and 8{\%} experienced grade 3 neurosensory toxicity. The overall response rate was 45{\%} (40{\%} on an intention to treat) including 10 complete remissions. Of 18 patients with FL, 9 responded with 4 complete response. The median time to treatment response for FL was 12 weeks, whereas the median time to treatment response for other subtypes of non-Hodgkin's lymphoma was only 4 weeks. Conclusions: These data suggest that bortezomib has significant single agent activity in patients with FL, and that longer durations of treatment may improve overall response.",
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T1 - Time to treatment response in patients with follicular lymphoma treated with bortezomib is longer compared with other histologic subtypes

AU - O'Connor, Owen A.

AU - Portlock, Carol

AU - Moskowitz, Craig

AU - Hamlin, Paul

AU - Straus, David

AU - Gerecitano, John

AU - Gonen, Mithat

AU - Dumitrescu, Otilia

AU - Sarasohn, Debra

AU - Butos, John

AU - Neylon, Ellen

AU - Cortelli, Barbara Mac Gregor

AU - Blumel, Susan

AU - Evens, Andrew M.

AU - Zelenetz, Andrew D.

AU - Wright, John

AU - Cooper, Brenda

AU - Winter, Jane

AU - Vose, Julie Marie

PY - 2010/1/15

Y1 - 2010/1/15

N2 - Purpose: To determine the antitumor activity of the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma. Experimental Design: Patients with follicular lymphoma (FL), marginal zone lymphoma, mantle cell lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, and Waldenstrom's macroglobulinemia were eligible for study. Bortezomib was given at a dose of 1.5 mg/m2 as an i.v. push on days 1, 4, 8, and 11 of a 21-day cycle. Eligibility included the following: (a) no more than three prior therapies, (b) at least 1 month since prior chemotherapy, (c) measurable disease, and (d) an absolute neutrophil count of >1,000/μL and a platelet count >50,000/μL for the first dose of any cycle. Results: Seventy-seven patients were registered, of which 69 were assessable for response based on the completion of two cycles of therapy. Subtypes included FL (59.5%), mantle cell lymphoma (52%), small lymphocytic lymphoma/chronic lymphocytic leukemia (16.2%), marginal zone lymphoma (21.6%), and one Waldenstrom's macroglobulinemia. The median number of prior therapies was three. Themost common grade 3 toxicity was lymphopenia (35%) and thrombocytopenia (31%). Twenty-five patients experienced grade ≤2 sensory neuropathy (32), and 8% experienced grade 3 neurosensory toxicity. The overall response rate was 45% (40% on an intention to treat) including 10 complete remissions. Of 18 patients with FL, 9 responded with 4 complete response. The median time to treatment response for FL was 12 weeks, whereas the median time to treatment response for other subtypes of non-Hodgkin's lymphoma was only 4 weeks. Conclusions: These data suggest that bortezomib has significant single agent activity in patients with FL, and that longer durations of treatment may improve overall response.

AB - Purpose: To determine the antitumor activity of the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma. Experimental Design: Patients with follicular lymphoma (FL), marginal zone lymphoma, mantle cell lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, and Waldenstrom's macroglobulinemia were eligible for study. Bortezomib was given at a dose of 1.5 mg/m2 as an i.v. push on days 1, 4, 8, and 11 of a 21-day cycle. Eligibility included the following: (a) no more than three prior therapies, (b) at least 1 month since prior chemotherapy, (c) measurable disease, and (d) an absolute neutrophil count of >1,000/μL and a platelet count >50,000/μL for the first dose of any cycle. Results: Seventy-seven patients were registered, of which 69 were assessable for response based on the completion of two cycles of therapy. Subtypes included FL (59.5%), mantle cell lymphoma (52%), small lymphocytic lymphoma/chronic lymphocytic leukemia (16.2%), marginal zone lymphoma (21.6%), and one Waldenstrom's macroglobulinemia. The median number of prior therapies was three. Themost common grade 3 toxicity was lymphopenia (35%) and thrombocytopenia (31%). Twenty-five patients experienced grade ≤2 sensory neuropathy (32), and 8% experienced grade 3 neurosensory toxicity. The overall response rate was 45% (40% on an intention to treat) including 10 complete remissions. Of 18 patients with FL, 9 responded with 4 complete response. The median time to treatment response for FL was 12 weeks, whereas the median time to treatment response for other subtypes of non-Hodgkin's lymphoma was only 4 weeks. Conclusions: These data suggest that bortezomib has significant single agent activity in patients with FL, and that longer durations of treatment may improve overall response.

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