Estudio primario

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Perifosine plus bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma previously treated with bortezomib: results of a multicenter phase I/II trial.

Año 2011
Revista Journal of clinical oncology : official journal of the American Society of Clinical Oncology
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PURPOSE:

Novel agents have improved patient outcome in relapsed or relapsed/refractory multiple myeloma (MM). Preclinical data show that the novel signal transduction modulator, perifosine, enhances the cytotoxicity of dexamethasone and bortezomib. Clinical data suggest that perifosine in combination with dexamethasone has activity in relapsed or relapsed/refractory MM.

PATIENTS AND METHODS:

In a phase I/II study, perifosine in combination with bortezomib with or without dexamethasone was prospectively evaluated in 84 patients with relapsed or relapsed/refractory MM. All were heavily pretreated and bortezomib exposed; 73% were refractory to bortezomib, and 51% were refractory to bortezomib and dexamethasone. The dose selected for the phase II study was perifosine 50 mg/d plus bortezomib 1.3 mg/m(2), with the addition of low-dose dexamethasone at 20 mg if progression occurred on perifosine plus bortezomib alone.

RESULTS:

An overall response rate (ORR; defined as minimal response or better) of 41% was demonstrated with this combination in 73 evaluable patients, including an ORR of 65% in bortezomib-relapsed patients and 32% in bortezomib-refractory patients. Therapy was generally well tolerated; toxicities, including gastrointestinal adverse effects and fatigue, proved manageable. No treatment-related mortality was seen. Median progression-free survival was 6.4 months, with a median overall survival of 25 months (22.5 months in bortezomib-refractory patients).

CONCLUSION:

Perifosine-bortezomib ± dexamethasone demonstrated encouraging activity in heavily pretreated bortezomib-exposed patients with advanced MM. A phase III trial is underway comparing perifosine-bortezomib plus dexamethasone with bortezomib-dexamethasone in patients with relapsed/refractory MM previously treated with bortezomib.

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Estudio primario

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Bortezomib or high-dose dexamethasone for relapsed multiple myeloma.

Año 2005
Revista The New England journal of medicine
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BACKGROUND:

This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies.

METHODS:

We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3 mg per square meter of body-surface area) on days 1, 4, 8, and 11 for eight three-week cycles, followed by treatment on days 1, 8, 15, and 22 for three five-week cycles, or high-dose dexamethasone (40 mg orally) on days 1 through 4, 9 through 12, and 17 through 20 for four five-week cycles, followed by treatment on days 1 through 4 for five four-week cycles. Patients who were assigned to receive dexamethasone were permitted to cross over to receive bortezomib in a companion study after disease progression.

RESULTS:

Patients treated with bortezomib had higher response rates, a longer time to progression (the primary end point), and a longer survival than patients treated with dexamethasone. The combined complete and partial response rates were 38 percent for bortezomib and 18 percent for dexamethasone (P<0.001), and the complete response rates were 6 percent and less than 1 percent, respectively (P<0.001). Median times to progression in the bortezomib and dexamethasone groups were 6.22 months (189 days) and 3.49 months (106 days), respectively (hazard ratio, 0.55; P<0.001). The one-year survival rate was 80 percent among patients taking bortezomib and 66 percent among patients taking dexamethasone (P=0.003), and the hazard ratio for overall survival with bortezomib was 0.57 (P=0.001). Grade 3 or 4 adverse events were reported in 75 percent of patients treated with bortezomib and in 60 percent of those treated with dexamethasone.

CONCLUSIONS:

Bortezomib is superior to high-dose dexamethasone for the treatment of patients with multiple myeloma who have had a relapse after one to three previous therapies.

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Revisión sistemática

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Bortezomib-induced acute congestive heart failure: a case report and review of literature.

Año 2014
Autores Subedi A , Sharma LR , Shah BK
Revista Annals of hematology
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Estudio primario

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Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma.

Año 2008
Revista The New England journal of medicine
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BACKGROUND:

The standard treatment for patients with multiple myeloma who are not candidates for high-dose therapy is melphalan and prednisone. This phase 3 study compared the use of melphalan and prednisone with or without bortezomib in previously untreated patients with multiple myeloma who were ineligible for high-dose therapy.

METHODS:

We randomly assigned 682 patients to receive nine 6-week cycles of melphalan (at a dose of 9 mg per square meter of body-surface area) and prednisone (at a dose of 60 mg per square meter) on days 1 to 4, either alone or with bortezomib (at a dose of 1.3 mg per square meter) on days 1, 4, 8, 11, 22, 25, 29, and 32 during cycles 1 to 4 and on days 1, 8, 22, and 29 during cycles 5 to 9. The primary end point was the time to disease progression.

RESULTS:

The time to progression among patients receiving bortezomib plus melphalan-prednisone (bortezomib group) was 24.0 months, as compared with 16.6 months among those receiving melphalan-prednisone alone (control group) (hazard ratio for the bortezomib group, 0.48; P<0.001). The proportions of patients with a partial response or better were 71% in the bortezomib group and 35% in the control group; complete-response rates were 30% and 4%, respectively (P<0.001). The median duration of the response was 19.9 months in the bortezomib group and 13.1 months in the control group. The hazard ratio for overall survival was 0.61 for the bortezomib group (P=0.008). Adverse events were consistent with established profiles of toxic events associated with bortezomib and melphalan-prednisone. Grade 3 events occurred in a higher proportion of patients in the bortezomib group than in the control group (53% vs. 44%, P=0.02), but there were no significant differences in grade 4 events (28% and 27%, respectively) or treatment-related deaths (1% and 2%).

CONCLUSIONS:

Bortezomib plus melphalan-prednisone was superior to melphalan-prednisone alone in patients with newly diagnosed myeloma who were ineligible for high-dose therapy. (ClinicalTrials.gov number, NCT00111319.)

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Estudio primario

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An observational, retrospective analysis of retreatment with bortezomib for multiple myeloma.

Año 2008
Revista Clinical lymphoma & myeloma
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PURPOSE:

The aim of this retrospective chart review of patients with multiple myeloma (MM) was to describe patterns of retreatment with bortezomib-based therapy and responses to retreatment in a community-based setting.

PATIENTS AND METHODS:

Data were retrospectively extracted from the medical records of patients treated in US Oncology-affiliated community oncology clinics who received 2 separate treatments with bortezomib-based therapy. Eligible patients had > or = 60 days between treatments and > or = 4 bortezomib doses during initial treatment. Responses were determined primarily by laboratory values. Response categories included (1) very good partial response (VGPR), > or = 90% M-protein decrease; (2) partial response (PR), 50%-89% decrease; and (3) less than PR (< PR), < 50% decrease, excluding progressive disease (PD).

RESULTS:

Retreatment response data were available for 82 patients; 5 (6%) had VGPR, 12 (15%) had PR, 52 (63%) had < PR, 5 (6%) had PD, and 8 (10%) died. Among 62 patients with response assessments for initial treatment and retreatment, VGPR/PR rates to retreatment were 44%, 23%, and 13% among patients with VGPR, PR, and < PR to initial treatment, respectively. Median time between bortezomib treatments was 9.7 months; 29% of patients received non-bortezomib therapy between treatments. The most common treatment pattern (58% of patients) was single-agent bortezomib at initial treatment and retreatment. Toxicity contributed to discontinuation in 38% of patients during initial treatment and 22% during retreatment; rates of neuropathy contributing to discontinuation were 18% and 6%, respectively.

CONCLUSION:

Retreatment with bortezomib-based therapy is feasible, with predictable toxicities. This observational analysis supports bortezomib alone or in combination as a retreatment option after initial bortezomib treatment in patients with relapsed MM.

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Estudio primario

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A phase 2 study of bortezomib in relapsed, refractory myeloma.

Año 2003
Revista The New England journal of medicine
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BACKGROUND:

Bortezomib, a boronic acid dipeptide, is a novel proteasome inhibitor that has been shown in preclinical and phase 1 studies to have antimyeloma activity.

METHODS:

In this multicenter, open-label, nonrandomized, phase 2 trial, we enrolled 202 patients with relapsed myeloma that was refractory to the therapy they had received most recently. Patients received 1.3 mg of bortezomib per square meter of body-surface area twice weekly for 2 weeks, followed by 1 week without treatment, for up to eight cycles (24 weeks). In patients with a suboptimal response, oral dexamethasone (20 mg daily, on the day of and the day after bortezomib administration) was added to the regimen. The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee.

RESULTS:

Of 193 patients who could be evaluated, 92 percent had been treated with three or more of the major classes of agents for myeloma, and in 91 percent, the myeloma was refractory to the therapy received most recently. The rate of response to bortezomib was 35 percent, and those with a response included 7 patients in whom myeloma protein became undetectable and 12 in whom myeloma protein was detectable only by immunofixation. The median overall survival was 16 months, with a median duration of response of 12 months. Grade 3 adverse events included thrombocytopenia (in 28 percent of patients), fatigue (in 12 percent), peripheral neuropathy (in 12 percent), and neutropenia (in 11 percent). Grade 4 events occurred in 14 percent of patients.

CONCLUSIONS:

Bortezomib, a member of a new class of anticancer drugs, is active in patients with relapsed multiple myeloma that is refractory to conventional chemotherapy.

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Estudio primario

No clasificado

Feasibility and efficacy of bortezomib re-treatment in multiple myeloma.

Año 2007
Autores Ciolli, S , Leoni, F , Casini, C
Revista Haematologica
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Estudio primario

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Bortezomib-associated tumor lysis syndrome in multiple myeloma.

Año 2008
Autores Furtado M , Rule S
Revista Leukemia & lymphoma
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Estudio primario

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Bortezomib-bendamustine-dexamethasone for treatment of relapsed/refractory myeloma

Año 2011
Revista Haematologica
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Bendamustine with bortezomib and dexamethasone was evaluated in 79 patients with relapsed/refractory multiple myeloma. Median age was 64 (range 40-80) years and patients had a median of 2 (range 1-6) prior treatment lines. Bendamustine 70 mg/m2, day 1 and 4, bortezomib 1.3mg/m2 days 1, 4, 8, 11 intravenously, and dexamethasone 20 mg, days 1, 4, 8, and 11, q 28 days, was given for up to 8 cycles. Primary endpoint was response rate (ORR) and secondary endpoints were progression-free survival (PFS), overall survival (OS), time to response and toxicity. ORR was 60.9%, and when minor responses were included, 75.9%. Median time to response was 31 days (111 to best response). ORR rate was similar in patients previously exposed to bortezomib, lenalidomide and to both bortezomib and lenalidomide. PFS was 9.7 and OS 25.6 months. Multivariate analysis showed high LDH, ≥3 prior treatment lines and low platelet counts correlating with short survival. Grade 3/4 thrombopenia and G 3/4/5 infections were noted in 38% and 23% respectively. Grade ≤ 2 polyneuropathy increased from 19% at baseline to 52% at cycle 8 and grade 4 from 0 to 7%. Bendamustine-bortezomib-dexamethasone is active and well tolerated in patients with relapsed/refractory myeloma. This study is registered in the EudraCT data base (Nr. 2008-006421-13).

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Resumen estructurado de revisiones sistemáticas

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Bortezomib in multiple myeloma and lymphoma: a clinical practice guideline

Año 2007
Revista Database of Abstracts of Reviews of Effects (DARE)
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