Serum Free Light Chain Ratio (FLCr) Is a Powerful Prognostic Factor For Survival In Newly Diagnosed Multiple Myeloma (MM) Eligible For High Dose Melphalan (HDM)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1873-1873
Author(s):  
Graça Esteves ◽  
Manuel L Neves ◽  
Helena Martins ◽  
Carlos M. Martins ◽  
Maria Joao Costa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Prognostic Factor ◽  
Light Chain ◽  
Prognostic Value ◽  
Stage Ii ◽  
Newly Diagnosed ◽  
Baseline Serum ◽  
Significant Difference

Abstract Introduction MM is a B cell malignancy characterized by the presence of a monoclonal immunoglobulin (Ig) in the serum and/or urine produced by clonal plasma cells. MM has a variable outcome depending on age, stage and cytogenetic abnormalities. FLCr 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), namely the heterogeneous stage II. In the era of new therapeutic agents trending to personalized therapy, its prognostic value needs to be proved. Purpose To evaluate the prognostic value of baseline serum FLCr on outcome of patients with newly diagnosed MM eligible for HDM treated with thalidomide or bortezomib based regimens. Methods This is a retrospective study, from January 2005 to December 2012. We analyzed 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 drew at diagnosis before treatment, 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 bortezomib based regimen (64,7%), with doxorubicin and dexamethasone (PAD) in 55 patients (53,9%), with cyclophosphamide and dexamethasone (Cy-Bor-D) in 11 patients (10,8%) or thalidomide, doxorubicin and dexamethasone (TAD) in 36 patients (35,3%). Median follow-up from diagnosis was 30 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 102 patients treated with thalidomide or bortezomib based-regimens eligible for HDM. Fifty one percent of patients were male and median age was 52 years (22-70y). The Ig type was IgG in 62,7%, IgA in 14,7%, IgD in 3,9%, light chains MM in 17,7% and non-secretory MM in 1,0% of patients. The median Hb level was 9,8 g/dL (5,3-16,7mg/L) and median serum albumin was 31,5 g/L (22,3-48,3g/L). Creatinine clearance <30ml/mn occurred in 18,6% of patients, 34,3% had elevated LDH and median β2-microglobulin was 6,61 mg/L (1,06-45,77mg/L). According to ISS, 39,2%% of patients were on stage I, 25,5%% on stage II and 35,3% on stage III. Clonal k light chain present in 58,8% of patients: 64,7% had abnormal FLCr (<0,03 or >32,00). Cytogenetic FISH analysis was performed in 86,3% of patients: 32,4% presented high-risk features. We observed a significant difference on overall survival (OS) and progression free survival (PFS) according to Mayo Clinic risk-factors: 0, not reached (NR), 1, NR, 2, 49 months and 3, 71 months for OS (P=0,000) and 0, 68 months, 1, 55 months, 2, 16 months and 3, 24 months for PFS (P=0,000). According the FLCr there was a significant advantage on OS for standard FLCr: NR vs 71 months (P=0,035). A trend to a better OS (P=0,061) was observed in stage II patients with standard FLCr but no significant difference at any stage. 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 eligible for HDM treated with thalidomide or bortezomib-based therapies. We fail to fully demonstrate FLCr prognostic value on ISS stage II patients, only a trend for better outcome with standard FLCr. Disclosures: Esteves: Janssen-Cylag and Celgene. Consultancy on the area of multiple myeloma and acute myeloid leukaemia: Consultancy. Raposo:Roche; lymphoproliferative diseases: Consultancy. Guerra:Novartis, Bristol-Myers Squibb and Amgen. Advisory bord meetings. Areas involved: Myeloproliferative neoplasms and acute leukaemia: Consultancy.

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

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3150-3150 ◽  
Author(s):  
Graça V Esteves ◽  
Manuel L Neves ◽  
Helena F Martins ◽  
Maria Joao Costa ◽  
Sara Valle ◽  
...  
Keyword(s):  
Risk Factors ◽  
Prognostic Factor ◽  
Light Chain ◽  
Mayo Clinic ◽  
Prognostic Value ◽  
Myeloproliferative Neoplasms ◽  
Stage Ii ◽  
Newly Diagnosed ◽  
Baseline Serum

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.

Bone Marrow Microcirculation Parameter Amplitude A of Contrast-Enhanced Dynamic MRI Is a Prognostic Factor for Progressive Multiple Myeloma for Patients with Low Beta2-Microglobulin.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5062-5062
Author(s):  
Jens Hillengass ◽  
Klaus Wasser ◽  
Axel Benner ◽  
Stefan Delorme ◽  
Christian Zechmann ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Prognostic Factor ◽  
Prognostic Value ◽  
International Standards ◽  
High Temporal Resolution ◽  
Significant Prognostic Factor ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Contrast Enhanced

Abstract Introduction: We have previously shown that contrast-enhanced dynamic magnetic resonance imaging (dMRI) microcirculation parameters Amplitude A and distribution rate constant kep are significantly increased in patients with multiple myeloma (MM) compared to healthy controls and correlate with osteolytic bone involvement. Furthermore an elevated Amplitude A is associated with a high plasmacell-infiltration and increased microvessel density in bone marrow. We now evaluated the prognostic value of changes in microcirculation of bone marrow as detected by dMRI for overall (OAS) and event free survival (EFS) in patients with MM. Methods: Between 1999 and 2001 62 patients with progressive MM requiring chemotherapy according to international standards (6 newly diagnosed patients, 56 patients with relapse or refractory disease) were investigated with dMRI of the lumbar spine. OAS and EFS were updated for all patients in February 2005. The estimated median follow up was 4.5 years. All patients underwent standardized dMRI with high temporal resolution (T1w-turboFLASH) before start of therapy. The contrast uptake was quantified using a two compartment model with the output parameters Amplitude A and distribution constant rate kep reflecting bone marrow microcirculation. To examine the prognostic value of the findings of dMRI we used the Proportional Hazards model as proposed by Cox. Results: We recorded a correlation with borderline significance (p-value 0.1) between Amplitude A and EFS. We did not find a correlation of dMRI parameters with OAS. The multivariable analysis of Beta2-Microglobulin, age, Lactat Dehydrogenase (LDH) and Albumin revealed Beta2-Microglobulin as the only statistically significant prognostic factor for EFS in this group of patients. When patients were classified according to high or low Beta2-Microglobulin, Amplitude A was able to provide significant additional information characterizing EFS. Patients with low Beta2-Microglobulin and increased Amplitude A had significant shorter EFS than patients with low Beta2-Microglobulin and low Amplitude A. Conclusion: Our investigations indicate that dMRI parameter Amplitude A which reflects the increased bone marrow microcirculation and angiogenesis is a novel prognostic factor for progressive multiple myeloma in patients with low Beta2-Microglobulin. So a more precise differentiation of patients may be possible through dMRI. The prognostic impact of dMRI for newly diagnosed myeloma patients and patients with monoclonal gammopathie with undetermined signifikance will now be evaluated in a prospective study.

The Ratio of Monoclonal to Polyclonal Immunoglobulins Assessed with the Hevylite Test Predicts Prognosis, Is Superior for Monitoring the Course of the Disease and Allows Detection of Monoclonal Immunoglobulin In Patients with Normal or Subnormal Involved Immunoglobulin Isotype

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4038-4038
Author(s):  
Heinz Ludwig ◽  
Ladan Mirbahai ◽  
Niklas Zojer ◽  
Arthur Bradwell ◽  
Stephen Harding
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Risk Stratification ◽  
Binding Site ◽  
Light Chain ◽  
Monoclonal Immunoglobulin ◽  
Immunoglobulin Isotype ◽  
Site Group ◽  
Risk Stratification Model

Abstract Abstract 4038 Parameters that appraise the prognosis of an individual multiple myeloma (MM) patient are essential for clinical guidance and treatment planning. Similarly important for clinical care are factors that assess variations in the course of the disease and that allow accurate measurement of residual monoclonal proteins. Presently, the International Staging System (ISS) stage, and cytogenetics are used for prognostication, EBMT or IMWG response criteria are applied for evaluation of response and of progressive disease, and conventional protein analytics including serum free light chain (FLC) measurement, serum protein electrophoresis (SPE) and immunofixation (IF) for detection of residual paraprotein. Here, we evaluate the prognostic relevance of the ratio of monoclonal to isotype matched polyclonal immunoglobulins for prognostication at start of therapy, for evaluation of response for long term follow up and for measurement of monoclonal immunoglobulin in patients with normal or below normal levels of the involved immunoglobulin isotype. 103 previously untreated patients with multiple myeloma were enrolled (35 IgGκ, 17 IgGλ, 29 IgAκ, 22 IgAλ). 39 (38%) presented with ISS stage I, 42 (41%) with stage II, and 22 (21%) with stage III disease; there was insufficient data to assign ISS in 2 cases. Median age was 67 (range: 32,86) years. Patients were enrolled from 1994 to 2007, either into a trial comparing thalidomide-dexamethasone with Melphalan-Prednisone or into a study comparing double with triple autologous transplantation after 4 cycles of VAD induction therapy. Patients were followed for a median of 13 months (range: 85 days -158 months). Immunoglobulin heavy/light chain (HLC) pairs were assessed by using polyclonal antibodies targeted at unique junctional epitopes between heavy chain and light chain constant regions of intact immunoglobulins using the Hevylite IgA kappa, IgA lambda, IgG kappa and IgG lambda kits (HevylitêO Binding Site, Birmingham, UK) on a Siemens BN̂OII Analyzer. Concentrations of conventional parameters such as IgA, IgG, ß2-microglobulin (β2-M), FLC, immunofixation, LDH, creatinine, were assessed by standard techniques. Survival analysis and Cox proportional hazards were performed using SPSS v18 program Median OS of the entire group was 37.9 months with 39 (37 %) of the103 (6 patients were lost to follow up) patients being alive at 4 years follow up. Univariate analysis revealed a correlation between OS and β2-M, (HR: 1.411, 95% CI: 1.369–4.248, p=0.002), the HLC ratio (HR: 1.9, 95% CI: 1.092–3.36, p=0.02), and LDH (HR:1.006, 95%CI 1.00–1.014, p=0.0396) but not with Albumin, age, and creatinine. In multivariate analysis, β2-M (HR: 1.9, 95% CI: 1.105–3.93, p=0.028), and the HLC ratio (HR: 1.89, 95% 1.092–3.362: x-y, p=0.039), were found as the only parameters correlating with survival. A three tiered risk stratification model utilizing ß2-M >3.5mg/L and HLC >median value had a greater prognostic value than ISS (p=0.001 v p=0.09). Patients with 0 risk factors (ß2-M <3.5mg/L, HLC ratio <median) had a 50% survival time of 118 months, patients with 1 risk factor (either ß2-M >3.5mg/L or HLC ratio >median) had a 50% survival of 53 months and those with both risk factors (ß2-M >3.5mg/L and HLC ratio >median) had a 50% survival of 29 months (p=0.001). During follow up 46 (45%) of the patients achieved normal or subnormal levels of their involved immunoglobulin isotype. Abnormal HLC ratios were identified in 35/46, interestingly 7/35 patients (IgA kappa: 2 pts, IgA lambda: 2pts. IgG kappa: 3pts) were negative by IFE, indicating that the hevylite test is more sensitive than IF in identifying residual disease. In addition in 7/35 patients HLC ratio indicated relapse when immunoglobulin levels where within normal ranges. In conclusion, the HLC ratio is highly prognostic. Furthermore, HLC analysis improved the detection of variations in the course of the disease and increased the diagnostic accuracy in patients with normal or subnormal levels of the involved isotype and even in patients shown to ne negative in IF. Determination of the HLC ratio seems to overcome a hitherto unmet need for improvement in assessment of response and of variations in the production of the monoclonal protein.Figure 1:Risk stratification model based upon ß2-M >3.5mg/L and HLC >medianFigure 1:. Risk stratification model based upon ß2-M >3.5mg/L and HLC >median Disclosures: Mirbahai: Binding Site Group Ltd: Employment. Bradwell:Binding Site: Equity Ownership, Patents & Royalties. Harding:Binding Site Group Ltd: Employment.

scholarly journals Smoldering Multiple Myeloma: Usefulness of Serum Heavy/Light Chain Measurements for the Evaluation of Evolving Pattern

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4514-4514
Author(s):  
Carlos Fernandez de Larrea ◽  
Ignacio Isola ◽  
Esther Moga ◽  
Maria Teresa Cibeira ◽  
Ester Lozano ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Prognostic Factors ◽  
Light Chain ◽  
Protein Level ◽  
Progressive Increase ◽  
M Protein ◽  
Smoldering Multiple Myeloma ◽  
Risk Of Progression

Abstract Introduction: Smoldering multiple myeloma (SMM) is an asymptomatic and biologically heterogeneous clonal plasma cell disorder. A number of prognostic factors to identify patients at a higher risk of progression have been described, such as the size of the M protein, proportion of abnormal bone marrow plasma cells (BMPCs), immunoparesis and serum free light chain (FLC) k/l ratio. More recently, isotype-specific uninvolved heavy and light chain (HLC) pair suppression measured with the Hevylite assay was also associated with an increased risk of progression. Recent studies have evaluated the key prognostic impact of an increase in M-protein levels during follow-up ("evolving" pattern). However, an important limitation could be the evaluation of M-protein level variations based on serum protein electrophoresis (SPE) in patients with a small size M-spike. The aim of this study was to prospectively analyze the changes in M-protein according to SPE and HLC measurements, as well as other risk factors for progression, in patients with SMM. Methods: Thirty patients newly diagnosed with SMM at a single institution from January 2014 through September 2017 were prospectively included in the study. For each patient, baseline levels of known prognostic factors (serum M-protein, serum and urine immunofixation, clonal BMPCs percentage, total immunoglobulins, involved/uninvolved FLC and involved/uninvolved HLC pairs) were recorded. During the follow up, M-protein level, FLC and isotype specific HLC pairs were also analyzed. Evolving change in M-protein level according to SPE was defined as ³ 10% increase within the first 6 months of diagnosis (if M-protein was ³ 30 g/L) and/or ³ 25% increase within the first 12 months (for any level of M-protein); evolving change according to HLC was defined as a ³ 10% increase in the involved pair. A sequential increase in each of three or more consecutive measurements from diagnosis was considered an evolving change regardless of its magnitude. Results: The clinical characteristics of the total of patients, as well as of the patients with evolving changes in M-protein according to HLC are summarized in Table 1. During the study period, 5/30 (17%) of patients demonstrated an evolving behavior of the M-protein according to SPE. Four of these patients (4/5) also showed a progressive increase in the M-protein in the HLC measurements. One patient showed stable HLC levels even though both the M-protein and the involved FLC progressively increased. This patient was of intermediate and low risk according to Mayo Clinic and PETHEMA scores, respectively. On follow up, no progressive suppression of the isotype-specific uninvolved HLC pair or increase in the FLC ratio was noted, and there have been no signs of progression after a follow up of 3 years. According to involved HLC-pair levels, 12/30 (40%) of patients demonstrated an evolving behavior. Five out of 7 patients that were not classified as evolving by SPE, were IgA isotype. Eight out of 12 patients showed severe isotype-specific suppression of the uninvolved HLC-pair (> 50% below lower level of normal) as well as a highly abnormal FLC ratio (<0.125 or >8). Three out of the 4 remaining patients showed either severe isotype-specific HLC pair suppression or highly abnormal FLC ratio in follow up measurements. Compared to patients with no "HLC-evolving pattern", evolving patients were more likely to have highly abnormal FLC ratios (90 vs. 33%, p=0.009), severe suppression of the other isotypes (64 vs. 19%, p=0,024), highly abnormal isotype-specific HLC ratios (67 vs. 33%, p=NS), severe isotype-specific HLC-pair suppression (75 vs. 50%, p=NS), and immunoparesis (67 vs. 39%p=NS). Five patients progressed to symptomatic multiple myeloma during follow up; 4 of them showed a progressive increase in the involved HLC pair from diagnosis. The remaining patient demonstrated a progressive increase in the involved HLC pair that started 19 months prior to progression, followed 4 months later with an increase in M-protein as measured by SPE. Conclusions: In our series, the Hevylite assay allowed us to identify patients with a progressive increase in M-protein (clonal heavy/light chain pair) that was not evident with SPE measurements. This "HLC evolving pattern" was associated with other risk factors for progression to symptomatic disease and with worsening of other prognostic parameters during follow up. Disclosures Rosinol: Janssen, Celgene, Amgen, Takeda: Honoraria. Bladé:Janssen: Honoraria.

scholarly journals Prognostic Value of Galectin-9 Relates to Programmed Death-Ligand 1 in Patients With Multiple Myeloma

2021 ◽  
Vol 11 ◽  
Author(s):  
Byung-Hyun Lee ◽  
Yong Park ◽  
JI-Hea Kim ◽  
Ka-Won Kang ◽  
Seung-Jin Lee ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Value ◽  
Immune Checkpoint Inhibitor ◽  
Plasma Cells ◽  
Cancer Type ◽  
Newly Diagnosed ◽  
Programmed Death ◽  
Significant Difference ◽  
Patient Prognosis ◽  
Cox Analysis

Galectin-9 (Gal-9) expression can be negatively or positively associated with cancer patient prognosis, depending on the cancer type. However, the nature of this relationship remains unclear in multiple myeloma. Therefore, we evaluated the prognostic value of Gal-9 and its relationship with the expression of PD-L1 molecule, the most widely studied immune checkpoint inhibitor, in patients with newly diagnosed multiple myeloma. Gal-9 and PD-L1 levels in bone marrow aspirate samples were evaluated using immunofluorescence assays. Gal-9 positivity was defined as having ≥1% Gal-9-expressing plasma cells. PD-L1 expression was categorized as low or high based on its median value. The median OS of patients with positive and negative Gal-9 expression was 42 months and not reached, respectively. However, no significant difference was observed in OS between the two groups (P = 0.10). Patients with high PD-L1 expression had OS times of 14 and 43 months in the positive and negative Gal-9 expression groups, respectively. In the high PD-L1 expression group, patients expressing Gal-9 had significantly worse OS than those negative for it (P = 0.019). Multivariable Cox analysis confirmed that Gal-9 expression could independently predict shortened OS (hazard ratio, 1.090; 95% confidence interval, 1.015–1.171; P = 0.018) in patients with high PD-L1 expression. However, in the low PD-L1 expression group, patients with high Gal-9 expression exhibited a trend toward better OS (P = 0.816). Our results indicate that the prognostic value of Gal-9 may be related to PD-L1 expression in patients with newly diagnosed multiple myeloma.

scholarly journals T(4; 14) Is Not a Poor Prognostic Factor for Newly Diagnosed Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation in New Drug Era

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 30-30
Author(s):  
Chuanying Geng ◽  
Guangzhong Yang ◽  
Wen Gao ◽  
Huijuan Wang ◽  
Yanchen Li ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Prognostic Factor ◽  
Propensity Score ◽  
Stem Cell Transplantation ◽  
Propensity Score Matching ◽  
Autologous Stem Cell Transplantation ◽  
Prognostic Value ◽  
Newly Diagnosed ◽  
New Drug

Background The prognostic value of t(4;14) in newly diagnosed multiple myeloma (MM) patients undergoing autologous stem cell transplantation (ASCT) remains controversial. We aimed to evaluate the prognostic value of t(4; 14) for newly diagnosed MM patients undergoing ASCT in new drug era. Methods We retrospectively analyzed 419 newly diagnosed MM patients under 66 years of age in Beijing Chaoyang hospital, Capital Medical University. The propensity score matching technique was used to reduce the bias between groups. Results Among 419 patients, 243 (58.0%) patients received ASCT after induction therapy including new drugs with 12 months. Patients with ASCT had significantly longer median overall survival (OS) (69.8 vs. 59.3 months, p=0.034) and progression-free survival (PFS) (35.0 vs. 23.9 months, p=0.001) than non-ASCT patients. Univariate Cox proportional hazards regression analyses showed that ASCT was correlated with longer OS (HR=0.720, 95%CI: 0.531-0.977, p=0.035) and PFS (HR=0.618, 95%CI: 0.470-0.814, p=0.001). The favorable effect of ASCT on PFS was confirmed in multivariate (HR=0.376, 95%CI: 0.195-0.723, p=0.003), but it had no impact on OS in multivariate analysis (p=0.289). In the propensity score matching analysis, 116 patients, 58 in each group, were identified. Among 116 matched patients, patients with ASCT had longer PFS (52.1 vs.23.3 months, p=0.002) and OS (89.2 vs.50.2 months, p=0.010). Among 121 patients received ASCT and t(4; 14) measurement by fluorescence in situ hybridization, 30 (24.8%) patients presented translocation t(4; 14). Univariate Cox analyses showed that t(4; 14) was not correlated with PFS (p=0.347) and OS (p=0.454). Multivariate Cox analyses also showed that t(4; 14) was not correlated with PFS (p=0.466) and OS (p=0.349). There was no significant difference in PFS (36.5 vs.37.0 months, p=0.344) or OS (54.0 vs.81.7 months, p=0.452) in ASCT patients with or without t(4;14). Conclusion These results demonstrated that ASCT was a favorable prognostic factor for newly diagnosed MM patients under 66 years of age, however, t(4; 14) had no prognostic value for newly diagnosed MM patients received ASCT in new drug era. Disclosures No relevant conflicts of interest to declare.

scholarly journals Elevated Serum Soluble Interleukin-2 Receptor Level Is a Useful Prognostic Factor for Disease-Specific Overall Survival in Patients with Newly Diagnosed Follicular Lymphoma before Initiation of Treatment

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3985-3985
Author(s):  
Kenji Nozaki ◽  
Hiroyuki Sugahara ◽  
Shuji Ueda ◽  
Jun Ishikawa ◽  
Shigeo Fuji ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Clinical Characteristics ◽  
Interleukin 2 ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
Soluble Interleukin 2 Receptor ◽  
Pretreatment Serum ◽  
Disease Specific

Introduction: Serum soluble interleukin-2 receptor (sIL-2R) is recognized as a tumor-related biomarker of malignant lymphomas, including follicular lymphoma (FL). The objective of this study is to assess the prognostic significance of pretreatment serum sIL-2R level for disease-specific overall survival (DSS) in patients with FL. Methods: We retrospectively analyzed medical records of our 10 individual institutions to identify all patients (pts) ≥ 18 years old with newly diagnosed FL between 01/01/2008 and 12/31/2018. Only pts with FL grade 1-3b, confirmed at pathological review, were included. Pts with histological transformation at diagnosis were excluded. Serum sIL-2R was determined by sandwich enzyme-linked immunosorbent assay. Clinical characteristics, therapies, response, relapse patterns and follow up status were collected and analyzed in the cohort. DSS was defined from the time of initial diagnosis to death due to lymphoma or last follow up. DSS was analyzed according to Kaplan Meier method and differences between subgroups were compared with log-rank test. Multivariate cox regression analysis was used to investigate associations of sIL-2R, FL International Prognostic Index (FLIPI) and progression or relapse within 24 months after diagnosis (POD24) with DSS. Serum levels of sIL-2R was measured before initiation of treatment and the data on the nearest date of the diagnostic biopsy within six months was adopted. Results: We recorded 565 pts and 535 pts of them with pretreatment serum sIL-2R levels available were included in the analysis with median age 64 years (range: 30-90) and 305 females (57%). Clinical characteristics are summarized in Table 1. The median of the serum sIL-2R level was 896 IU/mL (range: 145 - 23800). We decided an optimal cutoff value of 1800 IU/mL by using receiver operating characteristic (ROC) analysis, which showed it was 1830 IU/mL (AUC : 0.76, 95%CI : 0.67 - 0.84). Various poor prognostic indicators, such as bulky mass, increased LDH, ≥5 nodal lesions, poor performance status (PS), bone marrow invasion, FLIPI and FLIPI-2 high-risk, decreased Hb, advanced disease, high tumor burden, increased β2MG and existence of B symptoms, were strongly associated with high serum sIL-2R level (≥1800 IU/mL), and high sIL-2R level correlated with POD24 (P<0.001, Chi-squared test). The estimated 10-year DSS rate was 87.2% with a median follow up duration of 4.4 years. In pts with POD24 (96 pts, 18%), DSS was significantly worse than those with non-POD24; 64.3% vs 93.0% (P<0.001) and rituximab maintenance did not improve DSS in both groups (P=0.85 and 0.98, respectively). In patients with sIL-2R level of ≥1800 (high sIL-2R, 378 pts, 71%), DSS was significantly worse than those with sIL-2R level of <1800 IU/mL (low sIL-2R, 157 pts, 29%); 68.2% vs 96.0% (P<0.001), respectively (Figure 1). Multivariate analyses employing sex, PS, sIL-2R, FLIPI and POD24 demonstrated that high sIL-2R was an independent prognostic factor for DSS (HR : 2.88, 95% CI : 1.15-7.21, P<0.05). Regardless of POD24 status, pts with high sIL-2R had significantly worse DSS than those with low sIL-2R; 44.6% vs 91.5% in pts with POD24 (P<0.05) and 82.6% vs 96.8% in pts without POD24 (P<0.001), respectively. Among pts treated with rituximab plus anthracycline-containing chemotherapy as the 1st line regimen (222 pts, 41%), pts with high sIL-2R had significantly worse DSS than those with low sIL-2R; 68.1% vs 97.2% (P<0.001). Among pts treated with rituximab-bendamustine as the 1st line regimen (48 pts, 9%), there was no significant difference between high and low sIL-2R populations (P=0.2), however, among pts treated with bendamustine-containing regimen at least once in their life time (180 pts, 34%), there was significant difference between them; 63.1% vs 87.8% (P<0.05). Even in pts achieving complete metabolic response after 1st line treatment (178 pts, 33%), high pretreatment sIL-2R level was a significant factor affecting poor DSS; 75.9% vs 94.3% (P<0.05). Conclusions: High sIL-2R level ( ≥1800 IU/mL) is a significant and independent adverse prognostic factor for DSS in pts with newly diagnosed FL. This study provides us useful information to predict population with worse DSS before initiation of treatment. Disclosures Nozaki: Chugai: Honoraria; Celgene: Honoraria. Kida:Eisai Co., Ltd: Honoraria. Kosugi:Novartis Pharma Co.: Honoraria; Bristol-Myers Squibb Co.: Honoraria; Eisai Co., Ltd: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Kyowa Kirin Co., Ltd: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; ONO PHARMACEUTICAL CO., LTD.: Honoraria; NIPPON SHINYAKU CO.,LTD.: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Celgene K.K.: Honoraria; Pfizer Inc.: Honoraria. Shibayama:Astellas, Teijin, MSD, Shionogi, Eisai, Sumitomo Dainippon, Taiho, Nippon Shinyaku: Research Funding; Celgene, Chugai, Eisai, AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Takeda, Novartis, Janssen, Chugai, Eisai, Mundi Pharma, Ono, Otsuka, Kyowa Kirin, Sumitomo Dainippon, AstraZeneca, Avvie, DaiichiSankyo, Fujimoto, Nippon Shinyaku, Sanofi, Bristol-Myers Squibb, Pfizer: Honoraria.

Serum Kappa/Lambda Ratio, An Independent Prognostic Factor at Diagnosis and Serum Free-Light Chains Level, An Early Indicator of Relapse/Progression In Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2954-2954
Author(s):  
Mohamad Sobh ◽  
Stephane Morisset ◽  
Taoufik Guilli ◽  
Sophie Ducastelle-Lepretre ◽  
Fiorenza Barraco ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factor ◽  
Conflicts Of Interest ◽  
Fish Analysis ◽  
Cox Regression Analysis ◽  
Serum Free ◽  
Treatment Type ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 2954 Background: The serum free light chain (sFLC) analysis has been used for the diagnosis and monitoring of plasma cell dyscrasias and has proved its usefulness in disease treatment response in multiple myeloma (MM). Some studies have evaluated the prognostic value of the sFLC levels expressed as K/L ratio (sFLCR) at diagnosis. In contrast, performing this analysis during patient's follow up and on therapy is still not very well defined yet. Aim: Our first objective was to evaluate the impact of sFLCR, measured at diagnosis in MM patients, on the progression free survival (PFS) and overall survival (OS); the second objective was to assess the importance of sFLC analysis during the follow-up especially for relapse/progression detection comparing to concomitant monoclonal-protein (M-p) traditional serum protein electrophoresis (sPE). Methods: Between years 2002 and 2008, we have analysed 174 MM patients for which a concomitant measurement of sFLC and sPE was done during follow-up. Only 118 patients had the sFLCR analysis performed at diagnosis. The sFLC analysis was performed using the Freelite™ test from the Binding site on a BNIIÒ, Dade BehringÓ, and for sPE, analysis was done using a Paragon CZE 2000Ò, Beckman CoulterÓ. There were 92 (53%) males and 82 (47%) females, median age at diagnosis 57 years (34-72), 120 (69%) were IgG (87K&33L), 52 (30%) IgA (41K&11L) and 2 (1%) IgD (1K&1L). According to the ISS, there were 16 (9%) in stage I, 17 (10%) in stage II and 141 (81%) in stage III. Among 61 (35%) FISH analysis done, 31 (51%) detected a chromosome 13 deletion. Twenty six (15%) patients had renal insufficiency. According to the distribution of the different ratios at diagnosis, we have defined three groups: group1 (n=25): patients with 0.13<sFLCR<3.3 which represents the double of the normal range (0.26-1.65); group2 (n=63): patients with sFLCR>3.3 and group3 (n=30): patients with sFLCR<0.13.We also monitored the behaviour of sFLC and sPE in a way to early detect relapse/progression independently of treatment type. Kaplan Meier and cox regression analysis were performed to study the PFS and OS in different groups, slopes of the increase period corresponding to each measurement were compared using the student t-bilateral test with R statistical software. Results: After a median follow-up of 38 months [3.3-93.7], the 5-years OS for groups 1, 2 and 3 was 75% [56-100], 60% [47-76] and 40% [23-69] respectively; and the 5-years PFS was 69% [49-96], 43% [31-60] and 29% [15-54] respectively. The multivariate analysis studying age, ISS, sex, cytogenetics and sFLCR, showed that both OS and PFS are worslty affected with a more abnormal sFLCR, hazard ratios (HR) in Figure1. After monitoring all patients, we observed 117 (67%) patients with relapse/progression and 57 (33%) patients were still in response to treatment. In 77 (66%) cases, relapse or progression was detected by concomitant increase of both sFLC and the M-p with a significant earlier increase for sFLC (Figure2A). In 17 (15%) patients, the relapse or progression was characterised by the only increase of sFLC without any increase of the M-p (Figure2B). Contrarily, in 5 (4%) patients there was only an increase of the M-p without increasing the sFLC (Figure2D). Finally, in 18 (15%) patients, the relapse or progression was revealed by the increase of M-p faster than the concerned sFLC (Figure2C). When comparing slopes of increasing sFLC to increasing M-p, we found a very high significant difference (p<0.001), thus showing that sFLC have a faster detection of relapse or progression. Conclusion: Our study has showed that abnormal sFLCR at diagnosis affects OS and more strongly the PFS independently of any other concomitant variable. In 81% of patients, sFLC analysis enabled an earlier detection of relapse/progression compared to sPE, this could be very important for early treatment intervention especially for high risk patients. Since there are no uniform recommendations for the use of this analysis during follow-up, we recommend its concomitant use with sPE, waiting for guidelines and we suggest that the sFLCR at diagnosis deserves more focus for its validation as a prognostic factor in MM. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document