title: Serum free immunoglobulin light chain fingerprint identifies a subset of newly diagnosed multiple myeloma patients with worse outcome.
abstract: 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.
authors.affiliation: Department of Hematology, Tel Aviv Sourasky Medical Center and Tel Aviv University, Tel Aviv, Israel.
authors.forename: Irit
authors.initials: I
authors.lastname: Avivi
authors.affiliation: Department of Hematology, Tel Aviv Sourasky Medical Center and Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yael C
authors.identifier: http://orcid.org/0000-0002-9061-7287
authors.initials: YC
authors.lastname: Cohen
authors.affiliation: Department of Hematology, Tel Aviv Sourasky Medical Center and Tel Aviv University, Tel Aviv, Israel.
authors.forename: Erel
authors.initials: E
authors.lastname: Joffe
authors.affiliation: Department of Hematology, Rambam Medical Center, Technion, Haifa, Israel.
authors.forename: Noam
authors.initials: N
authors.lastname: Benyamini
authors.affiliation: Department of Hematology, Rambam Medical Center, Technion, Haifa, Israel.
authors.forename: Viki
authors.initials: V
authors.lastname: Held-Kuznetsov
authors.affiliation: Department of Hematology, Tel Aviv Sourasky Medical Center and Tel Aviv University, Tel Aviv, Israel.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Trestman
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
authors.forename: Efstathios
authors.initials: E
authors.lastname: Kastritis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology* / Q000401:mortality; D011379:Prognosis; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D007147:Immunoglobulin Light Chains
keywords: light chain; myeloma; prognosis; secretory