Τίτλος:
Serum free immunoglobulin light chain fingerprint identifies a subset of newly diagnosed multiple myeloma patients with worse outcome
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Multiple myeloma (MM) is a multi–subclonal malignancy with relatively high heterogeneity. Patients who initially presented with both monoclonal-protein (MP) and free light chain (FLC) secretion but then relapsed with a light chain escape pattern have been shown to reflect disease clonal evolution and to bare a worse prognosis. We hypothesized that a discordant MP/FLC pattern at diagnosis may reflect a similar clonal evolution that had occurred prior to diagnosis of active myeloma, conferring a worse outcome. We analyzed 255 consecutive newly diagnosed MM patients who received first line bortezomib-based therapy between 2007 and 2014, hypothesizing that their MP/FLC fingerprint at diagnosis reflects clonal heterogeneity and, therefore, affects outcome. An involved FLC level ≥ 700 mg/L and MP ≥ 2.5 g/L were used as cutoffs for low vs high FLC and MP levels, respectively. Patients were divided into 4 subgroups according to their involved FLC and MP blood levels at diagnosis: HiLC and HiMP for patients with either a predominant FLC or a predominant MP, respectively, and HiLC-MP and LoLC-MP when both FLC and MP were increased or decreased, respectively. There were 68 (27%) patients with HiLC, which presented more often with International Staging System-3 stage (P <.0001). Multivariate analysis showed that HiLC was associated with a 5.1-fold risk for mortality in a multivariate model (95% confidence interval [CI], 1.34-19.68). Both HiLC and HiLC-MP phenotypes were associated with shorter progression-free survival (hazard ratio of 2.66 [95% CI, 1.33-5.32] and 2.82 [95% CI, 1.37-5.83], respectively), independently of other prognostic factors, including the use of autograft. Thus, we identified an LC predominant secretory fingerprint (HiLC phenotype) at diagnosis as a potential independent risk factor that may affect disease control and survival in newly diagnosed MM patients treated with bortezomib-based induction therapy; this may represent increased subclonal heterogeneity. Copyright © 2016 John Wiley & Sons, Ltd.
Συγγραφείς:
Avivi, I.
Cohen, Y.C.
Joffe, E.
Benyamini, N.
Held-Kuznetsov, V.
Trestman, S.
Terpos, E.
Dimopoulos, M.A.
Kastritis, E.
Περιοδικό:
Journal of Hematology & Oncology
Εκδότης:
John Wiley and Sons Ltd
Λέξεις-κλειδιά:
bortezomib; immunoglobulin light chain; lactate dehydrogenase; immunoglobulin light chain, adult; aged; anemia; Article; cancer chemotherapy; cancer diagnosis; cancer survival; female; human; kidney failure; major clinical study; male; mortality risk; multiple myeloma; overall survival; phenotype; priority journal; progression free survival; treatment outcome; cohort analysis; immunology; middle aged; mortality; multiple myeloma; prognosis; risk factor; very elderly, Adult; Aged; Aged, 80 and over; Cohort Studies; Female; Humans; Immunoglobulin Light Chains; Male; Middle Aged; Multiple Myeloma; Prognosis; Risk Factors; Treatment Outcome
