Efficacy and safety of once-weekly and twice-weekly bortezomib in patients with relapsed systemic AL amyloidosis: results of a phase 1/2 study

Reece, Donna; Hegenbart, Ute; Sanchorawala, Vaishali; Merlini, Giampaolo; Palladini, Giovanni; Bladé, Joan; Fermand, Jean Paul; Hassoun, Hani; Heffner, Leonard T.; Vescio, Robert; Liu, Kevin; Enny, Christopher; Esseltine, Dixie Lee; Velde, Helgi van de; Cakana, Andrew; Comenzo, Raymond L.

doi:10.1182/blood-2011-02-334227

Cited by 159 publications

(138 citation statements)

References 51 publications

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“…46 Several phase II clinical trials in relapsed/refractory patients have been performed with immunomodulatory agents or the proteasome inhibitor bortezomib as single agents or in combination with alkylating agents and steroids with promising results. 45,[47][48][49][50] However, the outcomes of these clinical trials are difficult to interpret because of the mix of patients with respect to disease status, prior initial therapy, extent of organ involvement and different ways of reporting results. For phase III studies in relapsed/refractory patients, stratification based on degree of organ disease is indicated.…”

Section: Study Populationsmentioning

confidence: 99%

Consensus guidelines for the conduct and reporting of clinical trials in systemic light-chain amyloidosis

et al. 2012

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Section: Study Populationsmentioning

confidence: 99%

Consensus guidelines for the conduct and reporting of clinical trials in systemic light-chain amyloidosis

et al. 2012

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“…15,16 A prospective phase I/II clinical trial of bortezomib as a single agent showed a hematologic response in approximately two thirds of relapsed/refractory patients with AL amyloidosis. 17,18 In this trial, tolerability in patients with cardiac involvement was good, but subjects with advanced disease were excluded. 19 A large retrospective study including 94 patients, most of whom were relapsed or refractory after previous treatment, confirmed the efficacy of this drug in combination with dexamethasone (overall hematologic response rate 71%).…”

Section: Introductionmentioning

confidence: 99%

Melphalan and dexamethasone with or without bortezomib in newly diagnosed AL amyloidosis: a matched case–control study on 174 patients

et al. 2014

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Oral melphalan and dexamethasone (MDex) is a standard treatment for patients with AL amyloidosis who are not eligible for stem cell transplantation at many referral centers. However, following encouraging reports on the activity of bortezomib combined with alkylators and dexamethasone, these combinations are being moved to frontline therapy. We compared the outcome of 87 patients treated with bortezomib plus MDex (BMDex) with that of 87 controls treated with MDex. Patients and controls were matched for age, cardiac and renal function and free light chain burden. A higher rate of complete responses was observed with BMDex (42 vs 19%), but this did not result in a survival improvement in the overall population. However, a significant survival advantage for BMDex was observed in patients without severe (New York Heart Association class III or IV) heart failure and with N-terminal pro-natriuretic peptide type-B <8500 ng/l. Patients treated with full-dose dexamethasone had similar response rates and survival whether they received bortezomib or not. Intermediate-risk patients who are not fit enough to receive high-dose dexamethasone are likely to take the greatest advantage from the addition of bortezomib to MDex.

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“…Significant obstacles for the timely delivery of bortezomib are peripheral neuropathy and thrombocytopenia, which can be reduced by subcutaneous or once per week administration [14,15]. When the twice-per-week bortezomib schedule was decreased to once per week, the rate of grade 3-4 peripheral neuropathy was significantly reduced from 28 to 8 %, without affecting efficacy [16]. VMP (Velcade, melphalan and prednisone) today is considered one of the standard approaches for elderly MM patients, and the once-weekly bortezomib schedule is a valid alternative strategy [17].…”

Section: Introductionmentioning

confidence: 99%

“…Since bortezomib is generally well tolerated at doses up to 1.6 mg/m 2 on a once-weekly schedule [16], we hypothesized that this dose of once-weekly bortezomib plus cyclophosphamide and dexamethasone (BCD) is as effective as the standard BCD, resulting in less toxicity and avoiding bortezomib treatment discontinuation, which eventually leads to decreased efficacy. The aim of this study is to evaluate the antitumor efficacy and safety profile of the BCD regimen as a frontline induction therapy in elderly patients with newly diagnosed MM, who were unfit for standard dose chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Once-Weekly 1.6 mg/m2 Bortezomib BCD Regimen in Elderly Patients with Newly Diagnosed Multiple Myeloma Who are Unfit for Standard Dose Chemotherapy

Tang

Yao

et al. 2016

Indian J Hematol Blood Transfus

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Bortezomib has shown anti-myeloma effects in combination with alkylating agents, but clinical benefits can be limited by neurotoxicity. There is less information on the efficacy and tolerability of once-weekly 1.6 mg/m 2 bortezomib combined with cyclophosphamide and dexamethasone (BCD) regimen in elderly patients with newly diagnosed multiple myeloma who are unfit for standard dose chemotherapy. Here, we report our experience of weekly 1.6 mg/m 2 intravenous bortezomib in this group of patients. Between March 2010 and February 2015, we treated 34 newly diagnosed elderly patients with the combination of bortezomib 1.6 mg/m 2 intravenously on days 1 and 8; cyclophosphamide 200 mg/m 2 intravenously on days 1-4; dexamethasone 20 mg intravenously on days 1-4, and 8-11. Among the 34 patients, 14 (41 %) responded with complete response (CR), 6 (18 %) with very good partial response (VGPR) and 10 (29 %) with partial response (PR). The overall response rates were 88 %. After 2 cycles of treatments, the survival of patients who attained a response of VGPR or CR was significantly longer than those with PR or resistance to BCD, for both progression-free survival (PFS) (21.4 vs. 10.6 months, p = 0.002) and overall survival (OS) (23.0 vs. 16.8 months, p = 0.043). The 2-year PFS and OS were 26.5 and 64.7 % respectively in these elderly multiple myeloma patients in our study. Grade 1/2 neuropathy was observed in 20 % of the cycles while grade 3/4 neuropathy was not observed. No patients withdrew due to neuropathy or other side effects. Onceweekly bortezomib at 1.6 mg/m 2 BCD regimen is both effective and safe in elderly patients with newly diagnosed multiple myeloma who are unfit for standard dose chemotherapy.

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Efficacy and safety of once-weekly and twice-weekly bortezomib in patients with relapsed systemic AL amyloidosis: results of a phase 1/2 study

Cited by 159 publications

References 51 publications

Consensus guidelines for the conduct and reporting of clinical trials in systemic light-chain amyloidosis

Consensus guidelines for the conduct and reporting of clinical trials in systemic light-chain amyloidosis

Melphalan and dexamethasone with or without bortezomib in newly diagnosed AL amyloidosis: a matched case–control study on 174 patients

Once-Weekly 1.6 mg/m2 Bortezomib BCD Regimen in Elderly Patients with Newly Diagnosed Multiple Myeloma Who are Unfit for Standard Dose Chemotherapy

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