This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Terpos, E. Articles by Zervas, K. Search for Related Content PubMed PubMed Citation Articles by Terpos, E. Articles by Zervas, K.

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

On behalf of the Greek Myeloma Study Group

Correspondence: Evangelos Terpos, Department of Hematology and Medical Research, 251 General Air Force Hospital, 3 Kanellopoulou street, Athens, 11525, Greece. E-mail:eterpos{at}hotmail.com

Background: Renal 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 Methods: We 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.

Results: In 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.

Conclusions: Serum 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.

This article has been cited by other articles:

				M. A. Dimopoulos, P. G. Richardson, R. Schlag, N. K. Khuageva, O. Shpilberg, E. Kastritis, M. Kropff, M. T. Petrucci, M. Delforge, J. Alexeeva, et al. VMP (Bortezomib, Melphalan, and Prednisone) Is Active and Well Tolerated in Newly Diagnosed Patients With Multiple Myeloma With Moderately Impaired Renal Function, and Results in Reversal of Renal Impairment: Cohort Analysis of the Phase III VISTA Study J. Clin. Oncol., December 20, 2009; 27(36): 6086 - 6093. [Abstract] [Full Text] [PDF]