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


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 beta(2)-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.
Terpos
Evangelos
E
Department of Hematology and Medical Research, 251 General Air Force Hospital, 3 Kanellopoulou street, Athens, 11525, Greece. eterpos@hotmail.com
Katodritou
Eirini
E
Tsiftsakis
Evangelos
E
Kastritis
Efstathios
E
Christoulas
Dimitrios
D
Pouli
Anastasia
A
Michalis
Eurydiki
E
Verrou
Evgenia
E
Anargyrou
Konstantinos
K
Tsionos
Konstantinos
K
Dimopoulos
Meletios A
MA
Zervas
Konstantinos
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D001897:Boronic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D000069286:Bortezomib; D055316:Cystatin C / Q000097:blood*; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D011446:Prospective Studies; D011719:Pyrazines / Q000008:administration & dosage / Q000627:therapeutic use*; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D001897:Boronic Acids; D055316:Cystatin C; D011719:Pyrazines; D000069286:Bortezomib