Bortezomib and Dexamethasone in Previously Untreated Multiple Myeloma Associated with Renal Failure and Reversal of Renal Failure

Malani, Ashok K.; Gupta, V. D.; Rangineni, Raj

doi:10.1159/000095876

Cited by 22 publications

(18 citation statements)

References 31 publications

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“…19 In other studies of bortezomib-based regimens investigators have also reported similar notable levels of RI reversal. 18,[20][21][22]33,34,36,37 In contrast to the VISTA trial, 19 in which advanced age together with an abnormal renal function (eGFR Ͻ 30 mL/min) represented negative factors for RI recovery, in our study logistic multivariate analysis indicated male sex, but not age, as predictors of renal function recovery, whereas the moderate RI was confirmed as an independent prognostic factor also in our series. However, it is interesting to note that both the rate of and the time to RI reversal did not differ significantly in the 2 arms.…”

Section: Vmpt-vt Vs Vmp In MM With Renal Impairment 5763contrasting

confidence: 70%

Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in untreated multiple myeloma patients with renal impairment

Morabito

Gentile

Mazzone

et al. 2011

Blood

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We assessed efficacy, safety, and reversal of renal impairment (RI) in untreated patients with multiple myeloma given bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide (VMPT-VT) maintenance or bortezomib-melphalan-prednisone (VMP). Exclusion criteria included serum creatinine > 2.5 mg/dL. In the VMPT-VT/VMP arms, severe RI (estimated glomerular filtration rate [eGFR] < 30 mL/min), moderate RI (eGFR 31-50 mL/ min), and normal renal function (eGFR > 50 mL/min), were 6%/7.9%, 24.1%/24.9%, and 69.8%/67.2%, respectively. Statistically significant improvements in overall response rates and progression-free survival were observed in VMPT-VT versus VMP arms across renal cohorts, except in severe RI patients. In the VMPT group, severe RI reduced overall survival (OS). RI was reversed in 16/63 (25.4%) patients receiving VMPT-VT versus 31/77 (40.3%) receiving VMP. Multivariate analysis showed male sex (P ‫؍‬ .022) and moderate RI (P ‫؍‬ .003) significantly predicted RI recovery. VMP patients achieving renal response showed longer OS. In both arms, greater rates of severe hematologic adverse events were associated with RI (eGFR < 50 mL/min), however, therapy discontinuation rates were unaffected. VMPT-VT was superior to VMP for cases with normal renal function and moderate RI, whereas VMPT-VT failed to outperform VMP in patients with severe RI, although the relatively low number of cases analyzed preclude drawing definitive conclusions. VMPT-VT had no advantage in terms of RI reversal over VMP. This study is registered at http://www. clinicaltrials.gov as NCT01063179. (Blood. 2011;118(22):5759-5766)

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Section: Vmpt-vt Vs Vmp In MM With Renal Impairment 5763contrasting

confidence: 70%

Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in untreated multiple myeloma patients with renal impairment

Morabito

Gentile

Mazzone

et al. 2011

Blood

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“…Steroids have been shown to increase the levels of Cys-C. 33 Thus this reduction as well as the normalization of serum Cr in 6/6 patients who had high Cr values pre-bortezomib may be explained by the positive effect of bortezomib on renal function of myeloma patients; an effect which has been recently described. [18][19][20]34,35 One aspect of Cys-C measurement is that Cys-C can be affected by other pathological conditions, such as thyroid dysfunction, 36 or the use of glucocorticoids that has been associated with higher concentrations of Cys-C. 37,38 These effects suggest that the generation of Cys-C may increase in settings of increased metabolic rate, perhaps as a result of increased cell turnover. In our cohort population, no patient had received any steroid therapy before sampling for Cys-C measurement.…”

Section: Discussionmentioning

confidence: 99%

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

Terpos¹,

Katodritou²,

Tsiftsakis³

et al. 2009

Haematologica

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BackgroundRenal impairment is a common complication of multiple myeloma. Cystatin-C is considered an accurate marker of glomerular filtration rate in several renal disorders. Microarray analysis has revealed that cystatin-C is one of the most highly up-regulated genes in multiple myeloma. The aim of this study was to evaluate the serum levels of cystatin-C in myeloma patients, explore possible correlations with clinical data, including survival, and assess the effect of bortezomib on cystatin-C in relapsed multiple myeloma. Design and MethodsWe measured serum cystatin-C in 157 newly diagnosed, previously untreated myeloma patients, in 28 patients with relapsed disease pre-and post-bortezomib therapy and in 52 healthy controls, using a latex particle-enhanced nephelometric immunoassay. ResultsIn newly diagnosed patients, cystatin-C was elevated and showed strong correlations with advanced ISS stage, extensive bone disease, high β2-microglobulin, high serum creatinine, and low creatinine clearance. Multivariate analysis revealed that only cystatin-C and lactate dehydrogenase had an independent prognostic impact on patients' survival. The combination of cystatin-C and lactate dehydrogenase revealed three prognostic groups of patients: a high-risk group (both elevated cystatin-C and lactate dehydrogenase) with a median survival of 24 months, an intermediate-risk group (elevated cystatin-C or elevated lactate dehydrogenase) with a median survival of 48 months and a low-risk group (both low cystatin-C and lactate dehydrogenase) in which median survival has not yet been reached (p<0.001). Cystatin-C could also identify a subset of ISS-II patients with worse outcome. Relapsed patients had higher cystatin-C levels even compared to newly diagnosed patients. Treatment with bortezomib produced a significant reduction of cystatin-C, mainly in responders. ConclusionsSerum cystatin-C is not only a sensitive marker of renal impairment but also reflects tumor burden and is of prognostic value in myeloma. Its reduction after treatment with bortezomib reflects bortezomib's anti-myeloma activity and possibly bortezomib's direct effect on renal function.Key words: multiple myeloma, renal impairment, cystatin-C, bortezomib, survival. Haematologica 2009; 94:372-379. doi:10.3324/haematol.2008 This is an open-access paper.Cystatin-C is an independent prognostic factor for survival in multiple myeloma and is reduced by bortezomib administration

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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: 98%

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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Bortezomib and Dexamethasone in Previously Untreated Multiple Myeloma Associated with Renal Failure and Reversal of Renal Failure

Cited by 22 publications

References 31 publications

Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in untreated multiple myeloma patients with renal impairment

Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in untreated multiple myeloma patients with renal impairment

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

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

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