Weekly and twice-weekly bortezomib in AL amyloidosis: Results of a phase II study.

Reece, D. E.; Hegenbart, Ute; Sanchorawala, Vaishali; Merlini, Giampaolo; Bladé, J; Liu, K.; Enny, Christopher; Velde, Helgi van de; Cakana, Andrew; Comenzo, Ray

doi:10.1200/jco.2010.28.15_suppl.8023

Cited by 3 publications

(8 citation statements)

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“…The median time to response was only 1.2 months, and the once-weekly bortezomib regimen was associated with lower neurotoxicity. The results of the phase II study 67 are reported in Table 3. Data from three international centers on 94 (18 previously untreated) patients treated with bortezomib with or without dexamethasone found a hematologic response in 71% with 25% CRs (47% CRs in previously untreated patients).…”

Section: Wwwjcoorgmentioning

confidence: 99%

Amyloidosis: Pathogenesis and New Therapeutic Options

Merlini

Seldin

Gertz

2011

JCO

438

334

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The systemic amyloidoses are a group of complex diseases caused by tissue deposition of misfolded proteins that results in progressive organ damage. The most common type, immunoglobulin light chain amyloidosis (AL), is caused by clonal plasma cells that produce misfolded light chains. The purpose of this review is to provide up-to-date information on diagnosis and treatment options for AL amyloidosis. Early, accurate diagnosis is the key to effective therapy, and unequivocal identification of the amyloidogenic protein may require advanced technologies and expertise. Prognosis is dominated by the extent of cardiac involvement, and cardiac staging directs the choice of therapy. Treatment for AL amyloidosis is highly individualized, determined on the basis of age, organ dysfunction, and regimen toxicities, and should be guided by biomarkers of hematologic and cardiac response. Alkylator-based chemotherapy is effective in almost two thirds of patients. Novel agents are also active, and trials are ongoing to establish their optimal use. Treatment algorithms will continue to be refined through controlled trials. Advances in basic research have led to the identification of new drug targets and therapeutic approaches, which will be integrated with chemotherapy in the future.

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Section: Wwwjcoorgmentioning

confidence: 99%

Amyloidosis: Pathogenesis and New Therapeutic Options

Merlini

Seldin

Gertz

2011

JCO

438

334

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“…CAN2007 was the first prospective phase 1/2 study of single-agent bortezomib in relapsed AL. Phase 1 findings 23,24 and primary phase 2 efficacy and safety results from the study after 10.2-to 37.7-month median follow-up across dose groups have been reported previously. 25 Here we report long-term outcome data at study closure after 51.8-month median follow-up (median, 46.1-66.1 months across dose groups), and highlight a small subset of patients who received prolonged bortezomib treatment of up to 66.8 months (5.6 years).…”

Section: Introductionmentioning

confidence: 54%

“…The study was conducted at 9 sites in Canada, France, Germany, Italy, Spain, and the United States between July 25, 2005, and March 9, 2009. 23,25 Study design has been reported previously. 23,25 During phase 1, patients sequentially received single-agent bortezomib at 0.7, 1.0, 1.3, or 1.6 mg/m 2 QW and then at 0.7, 1.0, or 1.3 mg/m 2 BIW.…”

Section: Methodsmentioning

confidence: 99%

“…Eligibility criteria have been reported previously 23,25 and are summarized in the supplemental Appendix available on the Blood Web site. In brief, patients $18 years of age with confirmed AL diagnosis, who had previously been treated and required further treatment of AL due to persistent clonal disease, were eligible.…”

Section: Patientsmentioning

confidence: 99%

“…23 Patients on the QW schedule received bortezomib on days 1, 8, 15, and 22 in 35-day cycles. Patients on the BIW schedule received bortezomib on days 1, 4, 8, and 11 in 21-day cycles.…”

Section: 25mentioning

confidence: 99%

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Long-term follow-up from a phase 1/2 study of single-agent bortezomib in relapsed systemic AL amyloidosis

Reece

Hegenbart

Sanchorawala

et al. 2014

Blood

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• Single-agent bortezomib produces durable hematologic responses and promising long-term overall survival in relapsed AL patients.• Once-weekly bortezomib is better tolerated and produces similar responses to twiceweekly bortezomib in relapsed AL patients.CAN2007 was a phase 1/2 study of once-and twice-weekly single-agent bortezomib in relapsed primary systemic amyloid light chain amyloidosis (AL) amyloidosis. Seventy patients were treated, including 18 and 34 patients at the maximum planned doses on the once-and twice-weekly schedules. This prespecified final analysis provides mature response and long-term outcomes data after 3-year additional follow-up since the last report. In the once-weekly 1.6 mg/m 2 and twice-weekly 1.3 mg/m 2 bortezomib groups, final hematologic response rates were 68.8% and 66.7%; 80% of patients in each group sustained their response for ‡1 year. One-year progression-free rates were 72.2% and 76.8%. Median overall survival (OS) was 62.1 months and not reached; 4-year OS rates were 75.0% and 63.0%. Low baseline difference in k/l free light-chain level was associated with higher hematologic complete response rates and longer OS. At data cutoff, 40 (57%) patients had received subsequent therapy, including 19 (27%) retreated with bortezomib, 11 (58%) of whom achieved complete or partial hematologic responses. Four patients received prolonged bortezomib for between 3.5 and 5.6 years, with no new safety concerns, highlighting the feasibility of long-term therapy. Single-agent bortezomib produced durable hematologic responses and promising long-term OS in relapsed AL amyloidosis. This trial was registered at www.clinicaltrials.gov as #NCT00298766. (Blood. 2014;124(16):2498-2506 IntroductionPrimary systemic amyloid light chain amyloidosis (AL) is a protein misfolding disorder in which a clonal plasma cell dyscrasia results in excessive production of abnormal immunoglobulin light chains.1-4 Extracellular deposition and toxicity of these fibril-forming abnormal light chains can lead to end-organ damage, particularly in the kidneys and heart, 1-4 and death. Suppression of the plasma cell dyscrasia and reduction or elimination of the production of amyloidogenic immunoglobulin light chains is the aim of AL treatment.1 Amyloid deposits can be resorbed and organ function restored on elimination of plasma cells secreting the abnormal light chains.1 Achievement of a hematologic response to therapy, particularly complete response (CR), is associated with improved organ function and prolonged survival. 5-8The plasma cell dyscrasia in AL is similar to that in multiple myeloma (MM).3,9 Thus, therapies that are effective in MM are typically used to treat AL.1 High-dose melphalan followed by stem cell transplantation (HDM-SCT) is highly effective in AL; however, many patients may be transplantation ineligible 10,11 due to age, poor performance status, and multiple organ involvement. Despite improvements in the management of transplantation in AL patients in recent years, the observed transplantation-associa...

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