Addition of cyclophosphamide and higher doses of dexamethasone do not improve outcomes of patients with AL amyloidosis treated with bortezomib

Kastritis, Efstathios; Gavriatopoulou, Maria; Ρούσσου, Μαρία; Fotiou, Despina; Ziogas, Dimitrios C.; Migkou, Magdalini; Eleutherakis‐Papaiakovou, Evangelos; Panagiotidis, Ioannis; Kanellias, Nikolaos; Psimenou, Erasmia; Papadopoulou, Elektra; Pamboucas, Constantinos; Gakiopoulou, Hariklia; Ntalianis, Argyrios; Tasidou, Anna; Giannouli, Stavroula; Terpos, Evangelos

doi:10.1038/bcj.2017.47

Cited by 31 publications

(17 citation statements)

References 35 publications

(31 reference statements)

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“…A recent study compared the effects of treating 101 patients with AL amyloidosis with VD (59 patients) or VCD (42 patients). The results indicate that for the VD regimen, low dexamethasone doses were equally as effective as higher doses; furthermore, efficacy was not improved by the addition of cyclophosphamide (VCD) [ 96 ]. A hematologic response was achieved in 68% of patients treated with VD and 78% treated with VCD ( p = 0.26).…”

Section: Bortezomib In Light Chain Amyloidosismentioning

confidence: 99%

Bortezomib for the Treatment of Hematologic Malignancies: 15 Years Later

Robak

2019

Drugs R D

114

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Bortezomib is a dipeptidyl boronic acid that selectively inhibits the ubiquitin proteasome pathway, which plays a role in the degradation of many intracellular proteins. It is the first-in-class selective and reversible inhibitor of the 26S proteasome, with antiproliferative and antitumor activity. It exerts its anti-neoplastic action mainly via the inhibition of the nuclear factor-κB pathway components associated with cell proliferation, apoptosis, and angiogenesis. The drug has revolutionized the treatment of multiple myeloma and, more recently, mantle cell lymphoma. In 2003, bortezomib received accelerated approval from the US Food and Drug Administration for the treatment of relapsed/refractory multiple myeloma and in 2008 for patients with previously untreated multiple myeloma. In 2006, bortezomib was approved for the treatment of refractory/relapsed mantle cell lymphoma and, in 2014, for previously untreated mantle cell lymphoma. Bortezomib has also demonstrated clinical efficacy both as a single drug and in combination with other agents in light chain amyloidosis, lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia, and peripheral T-cell lymphomas. Furthermore, continued clinical studies are required to confirm its value for patients with indolent and aggressive B-cell non-Hodgkin lymphomas and acute leukemias.

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Section: Bortezomib In Light Chain Amyloidosismentioning

confidence: 99%

Bortezomib for the Treatment of Hematologic Malignancies: 15 Years Later

Robak

2019

Drugs R D

114

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“…Melphalan is more effective in patients harboring t(11;14) and, combined with bortezomib, it is associated with a longer response [31]. Of note, a retrospective study showed that the addition of cyclophosphamide and a combination with higher doses of dexamethasone do not significantly improve the response rate or survival of patients treated with bortezomib [32].…”

Section: Upfront Conventional Treatmentmentioning

confidence: 99%

Conventional Therapy for Amyloid Light-Chain Amyloidosis

Milani¹,

Palladini²

2020

Acta Haematol

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The vast majority of patients with light-chain (AL) amyloidosis are not eligible for stem cell transplant and are treated with conventional chemotherapy. Conventional regimens are based on various combinations of dexamethasone, alkylating agents, proteasome inhibitors, and immunomodulatory drugs. The choice of these regimens requires a careful risk stratification, based on the extent of amyloid organ involvement, comorbidities, and the characteristics of the amyloidogenic plasma cell clone. Most patients are treated upfront with bortezomib and dexamethasone combined with cyclophosphamide or melphalan. Cyclophosphamide does not compromise stem cell mobilization and harvest and is more manageable in renal failure. Melphalan can overcome the effect of t(11; 14), which is associated with lower response rates and shorter survival in subjects treated with bortezomib and dexamethasone, or in combination with cyclophosphamide. Lenalidomide and pomalidomide are the mainstay of rescue treatment. They are effective in patients exposed to bortezomib, dexamethasone, and alkylators, but deep hematologic responses are rare. Ixazomib, alone or in combination with lenalidomide, increases the rate of complete responses in relapsed/refractory patients. Conventional chemotherapy regimens will represent the backbone for future combinations, particularly with anti-plasma-cell immunotherapy, that will further improve response rates and outcomes.

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“…We filtered a total of 1,406 articles, from which sixteen studies (Jaccard et al, 2008;Gibbs et al, 2009;Gillmore et al, 2009;Wechalekar et al, 2010;Wechalekar et al, 2013;Palladini et al, 2014;Venner et al, 2014;Kastritis et al, 2015;Milani et al, 2015;Gertz et al, 2016;Katoh et al, 2016;Kastritis et al, 2016;Milani et al, 2017;Kastritis et al, 2017;Shimazaki et al, 2018;Liu et al, 2019) involving 3,402 participants were ultimately selected for the analysis. Of the sixteen studies, three were RCTs Kastritis et al, 2016), two were prospective types (Wechalekar et al, 2010;Palladini et al, 2014), the other two were case-control types (Palladini et al, 2014;Milani et al, 2015), and the remaining nine were retrospective types Wechalekar et al, 2010;Wechalekar et al, 2013;Venner et al, 2014;Kastritis et al, 2015;Katoh et al, 2016;Kastritis et al, 2017;Shimazaki et al, 2018;Liu et al, 2019). The PRISMA flow diagram was presented in Figure 1.…”

Section: Baseline Characteristics Of Enrolled Studiesmentioning

confidence: 99%

Efficacy of Chemotherapies and Stem Cell Transplantation for Systemic AL Amyloidosis: A Network Meta-Analysis

Cai

Xu²,

et al. 2020

Front. Pharmacol.

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Background/Aims: The present Bayesian network meta-analysis (NMA) was to compare the efficacy of different chemotherapies and autologous stem cell transplantation (ASCT) in immunoglobulin light-chain (AL) amyloidosis. Methods:We systematically searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies compared the rates of hematological response (HR), complete response (CR), renal response, and cardiac response in AL amyloidosis patients.Results: There were three randomized controlled trials (RCTs) and thirteen observational controlled trials (OCTs) comprising 3,402 participants enrolled for the comparisons of seven treatments: melphalan + dexamethasone (MDex), high-dose melphalan followed by ASCT, bortezomib + melphalan + dexamethasone (BMDex), thalidomide + cyclophosphamide + dexamethasone (CTD), bortezomib + dexamethasone (BDex), bortezomib + cyclophosphamide + dexamethasone (CyBorD), cyclophosphamide + lenalidomide + dexamethasone (CLD). BMDex was ranked first in the aspect of both HR and CR, CTD induced the highest rate of renal response, and BDex was possibly the best treatment for the cardiac response. Conclusion:Although more data about safety and cost are needed, BMDex was recommended as the most efficient treatment for AL amyloidosis patients for enhancing the response rate for HR and CR.

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Addition of cyclophosphamide and higher doses of dexamethasone do not improve outcomes of patients with AL amyloidosis treated with bortezomib

Cited by 31 publications

References 35 publications

Bortezomib for the Treatment of Hematologic Malignancies: 15 Years Later

Bortezomib for the Treatment of Hematologic Malignancies: 15 Years Later

Conventional Therapy for Amyloid Light-Chain Amyloidosis

Efficacy of Chemotherapies and Stem Cell Transplantation for Systemic AL Amyloidosis: A Network Meta-Analysis

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