Cystatin-C is an independent prognostic factor for survival in multiple myeloma and is reduced by bortezomib administration

Terpos, Evangelos; Katodritou, Eirini; Tsiftsakis, Evangelos; Kastritis, Efstathios; Christoulas, Dimitrios; Pouli, Anastasia; Michalis, Eurydiki; Verrou, Evgenia; Anargyrou, Konstantinos; Tsionos, Konstantinos; Dimopoulos, Meletios Α.; Zervas, Konstantinos

doi:10.3324/haematol.2008.000638

Cited by 66 publications

(59 citation statements)

References 40 publications

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“…A multivariate analysis showed that response to multiple-myeloma therapy and baseline GFR were significantly associated with renal response (77). Additional data showing the activity of bortezomib alone and in combination in renally impaired patients, plus reversibility of renal impairment with bortezomib-based treatment, have been provided by numerous case series and case reports (20,(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88), as summarized in Tables 1-3.…”

Section: Bortezomibmentioning

confidence: 99%

Novel Therapeutic Agents for the Management of Patients with Multiple Myeloma and Renal Impairment

Chanan‐Khan

Miguel

Jagannath

et al. 2012

Clinical Cancer Research

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Renal impairment is a major complication of multiple myeloma. Patients presenting with severe renal impairment represent a greater therapeutic challenge and generally have poorer outcome. However, once patients with renal impairment achieve remission, their outcomes are comparable with those of patients without renal impairment. Therapies that offer substantial activity in this setting are needed. Bortezomib, thalidomide, and lenalidomide have substantially improved the survival of patients with multiple myeloma. Here we review the pharmacokinetics, activity, and safety of these agents in patients with renal impairment. Bortezomib can be administered at the full approved dose and schedule in renally impaired patients; similarly, no dose reductions are required with thalidomide. The pharmacokinetics of lenalidomide is affected by its renal route of excretion, and dose adjustments are recommended for moderate/severe impairment. Substantial evidence has emerged showing that these novel agents improve outcomes of patients with renal impairment, including impairment reversal. Bortezomib, thalidomide, and lenalidomide (at the recommended doses) are active options for patients with mild to moderate impairment, although limited data are available for thalidomide. Information on lenalidomide-based combinations is still emerging, but the available data indicate considerable activity. Substantial evidence indicates that bortezomib-high-dose dexamethasone with or without a third drug (e.g., cyclophosphamide, thalidomide, or doxorubicin) is an appropriate option for patients with any degree of renal impairment.

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Section: Bortezomibmentioning

confidence: 99%

Novel Therapeutic Agents for the Management of Patients with Multiple Myeloma and Renal Impairment

Chanan‐Khan

Miguel

Jagannath

et al. 2012

Clinical Cancer Research

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“…Importantly, however, preventive measures have been shown to reduce the incidence of ONJ by 75% [129]. Zervas et al have suggested that patients receiving zoledronic acid may have a higher risk of ONJ than patients treated with pamidronate [137], but conversely, zoledronic acid is probably more effective in counteracting the development of skeletal complications [138]. Current guidelines suggest that in the presence of stable MM, one should consider stopping bisphosphonates after 2 years of treatment, with a view to re-starting therapy in the context of recurrent MM.…”

Section: Bone Diseasementioning

confidence: 99%

Consensus statement from European experts on the diagnosis, management, and treatment of multiple myeloma: from standard therapy to novel approaches

Engelhardt

Kleber

Udi

et al. 2010

Leukemia & Lymphoma

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Original Citation:Consensus statement from European experts on the diagnosis, management, and treatment of multiple myeloma: from standard therapy to novel approaches. Terms of use:Open Access (Article begins on next page) Anyone can freely access the full text of works made available as "Open Access". Works made available under a Creative Commons license can be used according to the terms and conditions of said license. Use of all other works requires consent of the right holder (author or publisher) if not exempted from copyright protection by the applicable law. Availability: This is the author's manuscriptThis version is available http://hdl.handle.net/2318/81898 since This is an author version of the contribution published on: Questa è la versione dell'autore dell'opera: [August 2010, Vol. 51, No. 8 , Pages 1424-1443 (doi:10.3109/10428194.2010 ABSTRACTTreatment for multiple myeloma (MM) has changed beyond recognition over the past two decades. During the early 1980s, MM inevitably resulted in a slow progressive decline in quality of life until death after about 2 years, while today patients can expect a 50% chance of achieving a complete remission, median survival of 5 years, and a 20% chance of surviving longer than 10 years. An international expert opinion meeting (including members of the GIMEMA and DSMM study groups) was held in 2009. One of the outcomes of the meeting was the development of a consensus statement outlining contemporary optimal clinical practice for the treatment of MM. The international panel recommended that the state of the art therapy for MM should comprise: (a) evidence-based supportive care, (b) effective and well-tolerated chemotherapeutic regimens, (c) autologous hematopoietic stem cell transplant (ASCT) for patients suitable for intensive conditioning therapy, and (d) evidence-based incorporation of novel anti-MM agents. Maintenance strategies have also become increasingly important for the prolongation of remission after front-line therapies. In addition, improved understanding of the biology of MM has led to the development of novel biological therapeutic agents such as thalidomide, lenalidomide, bortezomib, and others. These agents specifically target intracellular mechanisms and interactions, such as those within the bone marrow microenvironment, and have been integrated into MM treatment. This report reviews recent clinical advances in the treatment strategies available for MM and provides an overview of the state of the art management of patients with MM.

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“…Serum cystatin C was also measured at the same timepoints on a Behring Nephelometer-II analyser using a latex particle-enhanced nephelometric immunoassay (Dade Behring, Liederbach, Germany), as previously described [13].…”

Section: Efficacy and Safety Assessmentsmentioning

confidence: 99%

Deferasirox effectively decreases iron burden in patients with double heterozygous HbS/β-thalassemia

et al. 2010

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Iron overload is present in several cases of double heterozygous HbS/beta-thalassemia (HbS/beta-thal). Deferasirox is an orally administered iron chelator which is effective on iron overloaded patients with transfusion-dependent anemia. The aim of this study was to investigate the efficacy and safety of deferasirox in HbS/beta-thal patients with iron overload. We evaluated 31 adult patients with HbS/beta-thal (14M/17F; median age 41 years) who had serum ferritin levels >1000 ng/mL and who were sporadically transfused. Total iron burden was monitored by measuring serum ferritin levels before and monthly after starting deferasirox, while liver iron concentration and cardiac iron burden were measured by magnetic resonance imaging (MRI) T2 and T2* parameters at baseline and 12 months after deferasirox treatment. Deferasirox managed to reduce the mean serum ferritin levels after 12 months of treatment from 1989±923 to 1008±776 ng/mL (P<0.001). This reduction was accompanied by a significant improvement on MRI T2* of the liver (from 3.9±3.2 to 5.8±3.1 ms; P<0.01) and by a comparable improvement of biochemical parameters of liver function. Mild nausea and diarrhoea of grade 1/2 were reported in 25% of patients within the first month of treatment, but did not re-occur. These data indicate that deferasirox provided effective control of iron levels (mainly of the liver) in minimally transfused patients with HbS/beta-thal, without significant adverse events, at similar doses to those studied widely for the treatment of patients with thalassemia syndromes.Response to Reviewers: I would like to thank the reviewer for the valuable comments about our paper entitled "Deferasirox effectively decreases iron burden in patients with double heterozygous HbS/beta-thalassemia". Please find below our answers to these comments. All changes have been bolded into the text.Reviewer #1: Comment 1. The manuscript was thoroughly revised and has remarkably improved. However, concerning two of the previous comments were incompletely answered. A more detailed answer will increase the comprehensibility of the corresponding parts of the paper. Certainly, it will be very easy for authors to add the missing information: As stated in the previous comment 5, for liver MRI, it would be helpful for the reader to know how the T2star values correspond to liver iron concentration given as mg/g or micromole/g dry or wet weight since at present the majority of institutions and colleagues are using these values and related cut-offs for the assessment of liver siderosis. Comment 2. (see previous comment 6): In "Methods" it is stated that: "The starting deferasirox dose was 10 or 20 mg/kg/day depending on baseline iron burden..." In "Results", it is written that "patients were treated with deferasirox at 10 and 20mg/kg/day? based on the number of transfusions?")? How was the "baseline iron burden defined" (according to "Results" by the number of transfusions) and what was the cut-off number of blood transfusions to decide for 20mg/kg/d? Answer: We tha...

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Cystatin-C is an independent prognostic factor for survival in multiple myeloma and is reduced by bortezomib administration

Cited by 66 publications

References 40 publications

Novel Therapeutic Agents for the Management of Patients with Multiple Myeloma and Renal Impairment

Novel Therapeutic Agents for the Management of Patients with Multiple Myeloma and Renal Impairment

Consensus statement from European experts on the diagnosis, management, and treatment of multiple myeloma: from standard therapy to novel approaches

Deferasirox effectively decreases iron burden in patients with double heterozygous HbS/β-thalassemia

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