Serum Free Light Chain Ratio (FLCr) Is a Powerful Prognostic Factor For Survival In Newly Diagnosed Multiple Myeloma (MM) In The Era Of New Agents Namely On ISS Stage II Patients
Authors: Esteves Graça V , Neves Manuel L , Martins Helena F , Costa Maria Joao , Valle Sara , Raposo João , Martins Carlos M. , Guerra Lurdes , Lopes Conceição , Mendes Susana , Alho Ana , Ferreira Rita , Viveiros Carolina , Espada Eduardo , Conde Inês , Alves Daniela , Lacerda Joao F , Polo Blanca , Proença Helena , Carmo José A 
Published: October 2019

Abstract

Introduction
MM is characterized by the presence of a monoclonal immunoglobulin in the serum and/or urine, produced by malignant plasma cells. MM has a highly uncertain evolution and prognostic depending on age, stage and cytogenetic abnormalities. FLC is a readily available laboratory test and has independent prognostic significance in all the plasma cell disease entities helping to clarify International Staging System (ISS). Its value in the era of new therapeutic drugs is to be proved.

Purpose
To determine the prognostic value of baseline serum FLCr in patients with newly diagnosed MM, consecutively treated with thalidomide or bortezomib based regimens.

Methods
This is a retrospective study, from July 2004 to December 2012. We studied the relationship of baseline FLCr with outcome and its contribution to clarify the prognostic value of ISS. Serum FLC levels were measured in frozen sera at initial diagnosis, using a latex-enhanced immunoassay (The Binding Site, Birmingham, UK) on a Beckman Coulter nephelometric analyzer. FLCr was calculated as k/λ (reference range: 0,26-1,65). Abnormal FLCr was defined of < 0,03 or > 32,00 and standard FLCr of 0,03-32. Patients have been staged by ISS and Mayo Clinic stratification. All patients received at least two cycles of a thalidomide based regimen, 91 patients (38,9%): thalidomide, doxorubicin, dexamethasone (TAD), 37 patients (15,8%) and melphalan/cyclophosphamide, thalidomide, prednisone (M/CTP), 54 patients (23,0%) or bortezomib based regimens, 143 patients (61,1%): bortezomib, doxorubicin and dexamethasone (PAD), 53 patients (22,6%), bortezomib, cyclophosphamide and dexamethasone (Cy-Bor-D), 7 patients (2,9%) and melphalan/cyclophosphamide, bortezomib, prednisone (M/CVP), 83 patients (35,6%). Median follow-up from diagnosis was 25 months. Follow-up was through the review of each patient’s complete medical records at our center. Statistical analysis was performed with SPSS 20 ®.

Results
We reviewed 234 patients consecutively treated. Male gender was 46,6% and median age was 67 years (22-84y). The Ig type was IgG in 59,4%, IgA in 22,2%, IgD in 1,7%, light chains MM in 15,4% and non-secretory MM in 1,3%. The median Hb level was 10,7g/dL (4,9-16,7g/dL) and serum albumin was 27,4 g/L (9,0-50-0g/L). Twenty five percent of patients had a creatinine clearance <30ml/mn, 30,1% elevated LDH and median β2-microglobulin was 4,08 mg/L (0,97-100,8mg/L). According to ISS, 35,0% of patients were on stage I, 28,2% on stage II and 36,8% on stage III. Mayo Clinic stratification revealed 21,4% with 0, 31,2% with 1, 28,2% with 2 and 19,2% 3 risk-factors. Sixty percent of patients had k light chain clonality: 50,9% had abnormal FLCr (< 0,03 or > 32,00) and 49,1% had standard FLCr 0,03-32,00. FISH was performed in 74,4% patients: 26,0% presented high-risk features. Overall survival (OS) and progression free survival (PFS) were significantly different according the patients presented 0, 1, 2 or 3 Mayo Clinic risk factors, with median survival times of 83, not reached (NR), 39 and 36 months, for OS, p=0,000, and 41, 41, 17 and 17 months for PFS, p=0,000. Patients with abnormal FLCr had similar outcome of standard FLCr. Patients in ISS II had significant different OS according the FLCr: 77 and 39 months for standard and abnormal FLCr, respectively, P=0,015. There was no such correlation on stages I and III.

Conclusions
Baseline serum FLCr associated to others risk-factors like serum β2-microglobuline and albumin is a powerful prognostic factor for survival in newly diagnosed MM treated with thalidomide or bortezomib-based therapies. FLCr helps to clarify the outcome of ISS stage II patients identifying a subgroup with clearly inferior outcome.

Disclosures:
Esteves: Yassen: Consultancy; Celgene: Consultancy. Raposo:Roche; lymphoproliferative diseases: Consultancy. Guerra:Novartis, Bristol-Myers Squibb and Amgen. Advisory bord meetings. Areas involved: Myeloproliferative neoplasms and acute leukaemia: Consultancy.