The novel proteasome inhibitor bortezomib (Velcade®) is approved for the treatment of multiple myeloma following at least one prior therapy. Recently, bortezomib was shown to be active in relapsed mantle cell lymphoma and some low grade B-cell non-Hodgkin’s lymphomas. We conducted a phase 2 trial to evaluate the overall response rate (ORR) following treatment with single agent bortezomib in patients with relapsed DLBCL. Non-hospitalized patients with measurable disease, and a Karnofsky Performance Score > 60%, were eligible for the trial if they had relapsed after or were refractory to their most recent chemotherapy. Patients had to be either not eligible for high dose chemotherapy with stem cell support or had already received a stem cell transplantation. The treatment schedule was: bortezomib 1.3 mg/m2 via intravenous bolus on days 1, 4, 8, and 11 of a 21-day cycle for up to 8 cycles. Responses were assessed using the International Workshop criteria (

J Clin Oncol
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1999
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1244
). Ten patients were enrolled in this trial with one screen failure. The mean age was 60 years (range 22 to 83). The study population was heavily pretreated with a mean of 4.6 (range 2 to 7) prior chemotherapy regimens. Three patients (33.3 %) had received high dose chemotherapy with stem cell transplantation. The mean number of treatment cycles received was 2.33 (range 1 to 8). One of nine patients had stable disease (SD) and completed all 8 treatment cycles whereas all other patients progressed while on study drug (PD). The treatment was well tolerated. Grade ≥ 3 AEs included thrombocytopenia, neutropenia, hyponatremia, and hyperkalemia. In summary, single agent bortezomib is not an active drug in heavily pretreated patients with relapsed/refractory DLBCL. Bortezomib has clinical activity as single agent in other lymphoma subtypes and there is at least additive preclinical and clinical activity in combination with other agents. Therefore, investigation of bortezomib-containing combination therapies might be considered in less heavily pretreated DLBCL patients.

Topics:
bortezomib, diffuse large b-cell lymphoma, chemotherapy regimen, hematopoietic stem cell transplantation, lymphoma, hodgkin's disease, hyperkalemia, hyponatremia, intravenous bolus, mantle-cell lymphoma

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2005, The American Society of Hematology
2005
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