Prognostic Value of Immunophenotyping in Multiple Myeloma: A Study by the PETHEMA/GEM Cooperative Study Groups on Patients Uniformly Treated With High-Dose Therapy

2008 ◽  
Vol 26 (16) ◽  
pp. 2737-2744 ◽  
Author(s):  
Gema Mateo ◽  
M. Angeles Montalbán ◽  
Maria-Belén Vidriales ◽  
Juan J. Lahuerta ◽  
Maria V. Mateos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Progression Free Survival ◽  
Study Groups ◽  
High Dose ◽  
Prognostic Impact ◽  
Free Survival ◽  
Multiparametric Flow Cytometry ◽  
Risk Of Progression ◽  
Bone Marrow Plasma

Purpose To analyze the prognostic impact of immunophenotyping in patients with multiple myeloma (MM). Patients and Methods We have prospectively analyzed the prognostic impact of antigenic markers, assessed by multiparametric flow cytometry, in a series of 685 newly diagnosed MM patients that were uniformly treated according to the GEM 2000 protocol. Results Our results show that expression of both CD19 and CD28 as well as the absence of CD117 were associated with a significantly shorter progression free-survival (PFS) and overall survival (OS). Interestingly, the CD28 expression correlated with t(14;16) and del(17p), while CD117-negative patients were associated with t(4;14) and del(13q). Simultaneous assessment of CD28 and CD117 antigens allowed stratification of patients with MM into three risk categories: poor risk (CD28 positive CD117 negative), intermediate (either both markers negative or both positive), and good risk (CD28 negative CD117 positive), with PFS rates of 30, 37, and 45 months, respectively (P = .01), and OS rates of 45, 68, and not reached, respectively (P = .0001). Conclusion To the best of our knowledge, this is the first prospective analysis in which the prognostic impact of a relatively high number of antigenic markers has been simultaneously analyzed in a large series of uniformly treated patients, showing that the expression of several antigens (particularly CD28 and CD117) on bone marrow plasma cells from patients with MM can help to identify patients at high risk of progression.

Prognostic Value of Immunophenotyping of Multiple Myeloma: A Study on 685 Patients Uniformly Treated with High-Dose Therapy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1472-1472
Author(s):  
Gema Mateo ◽  
Maria A. Montalban ◽  
Maria-Belén Vidriales ◽  
Juan J. Lahuerta ◽  
Maria-Victoria Mateos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
High Dose ◽  
Prognostic Impact ◽  
Prognostic Information ◽  
Free Survival ◽  
Multiparametric Flow Cytometry ◽  
Disease Characteristics ◽  
Antigenic Profile ◽  
Simultaneous Assessment

Abstract Analysis of the antigenic profile of malignant cells has shown to be a valuable tool for the diagnosis and the identification of prognostic markers in haematological malignancies. By contrast, in multiple myeloma (MM), immunophenotyping is rarely used in clinical practice. Moreover, conflicting results have been reported probably because they were based on short series of heterogeneously treated MM patients. In the present study, we have prospectively analysed the prognostic impact of antigenic markers, assessed by multiparametric flow cytometry, in a series of 685 newly diagnosed MM patients that were uniformly treated according to the GEM-2000 protocol. The results show that three antigenic markers (CD19, CD28 and CD117) afford prognostic information. The expression of both CD19 and CD28 as well as the absence of CD117 were associated with a significantly shorter progression free-survival (PFS) and overall survival (OS). Interestingly, the CD28 expression correlated with t(14;16) and Del(17p), while CD117 negative cases were associated with t(4;14) and Del(13q) as well as several other disease characteristics. The simultaneous assessment of CD28 and CD117 antigens, allowed stratification of myeloma patients into three risk categories: poor risk (CD28+CD117−), intermediate (either both markers negative or both positive), and good risk (CD28−CD117+), with PFS rates of 30, 37 and 45 months, respectively (p=0.01), and OS of 45, 68 and not reached, respectively (p=0.0001). To the best of our knowledge, this is the first prospective analysis in which the prognostic impact of a relatively high number of antigenic markers has been simultaneously analysed in a large series of uniformly treated patients.

The role of complete response in multiple myeloma

Blood ◽  
2009 ◽  
Vol 114 (15) ◽  
pp. 3139-3146 ◽  
Author(s):  
Jean-Luc Harousseau ◽  
Michel Attal ◽  
Herve Avet-Loiseau
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Dose ◽  
Prognostic Impact ◽  
Free Survival ◽  
Depth Of Response ◽  
The Impact ◽  
Good Partial Response

AbstractIn multiple myeloma (MM), the impact of complete response (CR) could be shown only after introduction of high-dose therapy plus autologous stem cell transplantation (ASCT). In the context of ASCT, achieving CR (negative immunofixation and normal bone marrow) or at least very good partial response is associated with longer progression-free survival and in most studies longer survival. With novel agents, high CR rates are achieved and this prognostic impact of CR is being shown as well, both in relapsed and in newly diagnosed MM. However the benefit of CR achievement depends on the type of treatment and is not identical for all patients. In elderly patients, treatments inducing more CR may be more toxic. Although CR achievement is necessary in patients with poor-risk disease, it might not be as critical for long survival in more indolent MM. CR achievement is not the only objective of treatment because it is possible to further improve the depth of response and the outcome by continuing treatment after CR achievement. Finally, there are several levels of CR and in the future it will be necessary to confirm the prognostic impact of immunophenotypic or molecular CR or of CR defined by imaging procedures.

Clinical Features, Outcome and Prognostic Factors For Survival and Evolution To Multiple Myeloma Of Solitary Plasmacytomas: A Report Of The Greek Myeloma Study Group In 97 Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3130-3130
Author(s):  
Eirini Katodritou ◽  
Evangelos Terpos ◽  
Argiris S. Symeonidis ◽  
Anastasia Pouli ◽  
Charikleia Kelaidi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Features ◽  
Plasma Cells ◽  
Surgical Excision ◽  
Novel Agents ◽  
High Dose ◽  
Solitary Plasmacytoma ◽  
Prognostic Impact ◽  
Free Survival

Abstract Solitary plasmacytoma (SP) is a rare plasma cell dyscrasia characterized by the presence of bone or extramedullary tumors consisting of monoclonal plasma cells, without evidence of systematic multiple myeloma (MM). The treatment of choice is local radiotherapy (RT) with or without surgical excision (SE). Our aim was to describe the clinical features, the outcome and prognosis of SP patients. Thus, we studied 97 consecutive patients, 65 with solitary bone plasmacytoma (SBP) and 32 with solitary extramedullary plasmacytoma (SEP), (M/F: 66/31, median age: 61 years, range 17-85 years) who were diagnosed and treated in 12 Greek Myeloma Centers; treatment was given according to each center’s local policy. Patients with SBP and SEP did not differ in age, gender, performance status (PS), Hb, CRP, LDH, calcium, beta2-microglobulin, renal function or impairment of humoral immunity (immunoparesis). Patients with SEP presented more often with serum or urinary monoclonal component (p<0.001 and p=0.004, respectively). The median size of SP was larger in patients with SBP compared to patients with SEP (5.5cm vs. 3cm; p=0.003). CD56 antigen was expressed more often on plasma cells of SBP biopsies (p=0.03). Eighteen (56.2%) patients with SEP presented with upper respiratory track plasmacytoma and 14 presented with plasmacytomas in other locations. In 26/65 patients (40%) with SBP, plasmacytoma was located in the vertebrae and 39 had plasmacytoma in other bones. Bisphosphonates were administered more frequently in SBP patients (p=0.001). There was no difference in the type of treatment (RT, conventional chemotherapy (CT) ± novel agents (NA), SE or combined treatment) between the 2 groups; 80 patients (82.5%) received RT alone or in combination with CT and/or SE, 7 patients (7.2%) received CT alone, 7 patients (7.2%) underwent only SE and 3 patients (3.1%) were treated with CT and SE. The median dose of radiation delivered was 40 Gy (range 24-55 Gy). Novel agent combinations were administered in 27/47 patients (57.4%) who received CT (bortezomib-based regimens: 46.8%); 13/47 (27.6%) patients treated with CT underwent high-dose therapy. Myelotoxicity, neurotoxicity and neutropenic infections presented more frequently in patients treated with CT (p<0.001, p=0.01, p=0.009, respectively). Objective response rate (≥PR) and complete response (CR) was 91.8% and 61.9%, respectively. There was no difference in response rates or median time to response (3 months, range 1-24 months) between patients with SBP or SEP. Overall, 38 (39.2%) patients relapsed (relapse of SP only: 14; progression to MM only: 16, relapse of SP and progression to MM: 8). After a median follow up of 60 months (range 3-264 months), 74 (76.3%) patients were alive, 13 (13.4%) were dead and 10 (10.3%) patients were lost to follow up. Overall survival (OS), although higher in SEP over SBP, did not reach statistical significance. The 10-year MM-free survival (MMFS) was 50% vs. 70% respectively, for patients with SBP vs. SEP (p=0.054). Ten-year OS for patients treated with RT± surgical excision was 81% vs. 70% for those treated with other therapies including CT± NA (p=0.3). Overall, the 10-year OS, plasmacytoma relapse-free survival (PRFS), progression-free survival (PFS) and MMFS was 78%, 58%, 43% and 59%, respectively. In the multivariate analysis PRFS and age predicted for OS (p=0.02, HR: 0.97; 95% CI: 0.94-0.99 and p=0.01, HR: 1.09; 95% CI: 1.017-1.16, respectively); 10-year OS for patients <60 vs. ≥60 years was 85% vs. 60% (p=0.02); patients with PRFS >24 vs. ≤24 months had a 10-year OS of 82% vs. 60% (p=0.01). Achievement of CR predicted positively for PRFS. Immunoparesis (n=24) predicted negatively for progression to MM. Chemotherapy including NA had no prognostic impact on OS, PRFS or MMFS. Our study demonstrated that patients with SP enjoy a prolonged OS that is favorably influenced by young age and PRFS. We also confirmed that patients with SBP progress more frequently to MM compared to SEP in the era of novel agents. Radiotherapy with or without SE remains the treatment of choice for SP. The additional use of systematic therapy including novel anti-myeloma agents increases toxicity without improving survival or decreasing the probability of SP relapse or progression to MM. Immunoparesis predicts for progression to MM. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Prediction Model for Cereblon Expression in Bone Marrow Plasma Cells Based on Blood Markers in Multiple Myeloma Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Byung-Hyun Lee ◽  
Ka-Won Kang ◽  
Min Ji Jeon ◽  
Eun Sang Yu ◽  
Dae Sik Kim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cells ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
High Serum ◽  
Free Survival ◽  
Serum Free Light Chain ◽  
Bone Marrow Plasma ◽  
Clinically Significant

BackgroundCereblon (CRBN) is a direct target of immunomodulatory drugs (IMiDs) and is known to be sensitive and responsive to IMiD therapy. We evaluated CRBN expression in bone marrow plasma cells and analyzed whether CRBN expression was associated with multiple myeloma prognosis. Lastly, we developed a nomogram model for predicting high CRBN expression based on clinically significant blood markers.MethodsWe evaluated 143 multiple myeloma patients (internal dataset) who underwent bone marrow examinations. For evaluating the prognostic ability of the nomogram model, two external cohorts (235 patients in external dataset 1 and 156 patients in external dataset 2) were analyzed. The expression of CRBN in bone marrow aspirate samples was evaluated using immunohistochemistry. High CRBN expression was defined as the study-defined H-score ≥6.ResultsIn the high CRBN group, the median progression-free survival (PFS) and overall survival (OS) of patients receiving the IMiD-based therapy and non-IMiD therapy were 29 and 10 months for PFS, and NR (not reached) and 54 months for OS, respectively. IMiD-based therapy was significantly associated with better PFS and OS outcomes. High CRBN expression was independently predicted by female sex, high serum free-light chain (FLC) ratio, higher serum M-protein level, and higher β2-microglobulin level. Based on these results, we constructed a new nomogram model to predict high CRBN expression and the effectiveness of IMiD therapy in multiple myeloma.ConclusionThis nomogram could improve the prognostic evaluation of myeloma patients exhibiting high CRBN expression treated with IMiD therapy and might help provide personalized treatment strategies to clinicians.

Prognostic Value of Circulating Plasma Cells in Monoclonal Gammopathy of Undetermined Significance

2005 ◽  
Vol 23 (24) ◽  
pp. 5668-5674 ◽  
Author(s):  
Shaji Kumar ◽  
S. Vincent Rajkumar ◽  
Robert A. Kyle ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Prognostic Value ◽  
Plasma Cells ◽  
Progression Free Survival ◽  
M Protein ◽  
Free Survival ◽  
Risk Of Progression ◽  
Plasma Cell Disorder ◽  
Undetermined Significance

Purpose Monoclonal gammopathy of undetermined significance (MGUS) progresses to multiple myeloma or another related plasma cell disorder (PCD) at a rate of approximately 1% per year. Identification of patients with MGUS at high risk of progression will allow development of preventive strategies. We studied the prognostic value of circulating plasma cells (PCs) in patients with MGUS to predict progression. Patients and Methods Patients were eligible for this retrospective analysis if they were seen at the Mayo Clinic between 1984 and 1997, were diagnosed with MGUS, and had an analysis of the peripheral blood for circulating PCs by the slide-based immunofluorescence method. Patients were observed for progression to another PCD. Results Three hundred twenty-five patients were eligible and 63 (19%) had circulating PCs. Patients with circulating PCs were twice as likely (hazard ratio, 2.1) to experience progression to another PCD (most commonly myeloma), compared with those without circulating PCs (95% CI, 1.1 to 4.3; P = .03). In patients with circulating PCs, the median progression-free survival was 138 months compared with a median not yet reached for those without circulating PCs (P = .028). The median overall survival also was shorter for those with circulating PCs. Other factors with prognostic value were high levels of M protein and non–immunoglobulin G heavy-chain type. Conclusion The presence of circulating PCs, especially when combined with other known prognostic factors such as M protein concentration and immunoglobulin isotype, identify a group of individuals with MGUS at higher risk of progression to overt multiple myeloma.

scholarly journals Symptomatic Outcome of CTDa In Multiple Myeloma Patients

KYAMC Journal ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 124-128
Author(s):  
Zulfia Zinat Chowdhury ◽  
Mohammad Ali ◽  
AKM Mynul Islam ◽  
Salina Haque ◽  
Tamanna Bahar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Cost Effective ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
Albumin Level ◽  
High Dose ◽  
Female Ratio ◽  
Stem Cell Rescue ◽  
Bone Marrow Plasma

Background: Multiple Myeloma (MM) represents approximately 15% of all hematological malignancies. Despite the use of high-dose chemotherapy followed by stem cell rescue MM remains incurable at present. The goal is to control the disease as much as possible, providing the best quality of life to patients for the longest duration. Currently, CTDa (attenuated Cyclophosphamide, Thalidomide, Dexamethasone) is the best option of treatment as it is cost-effective, with no need for hospitalization with a good response. Objective: To find out the symptomatic responses and toxicities of CTDa in Multiple Myeloma patients. Materials and Methods: 25 patients of newly diagnosed MM patients were treated in the Haematology Department, Bangabandhu Sheikh Mujib Medical University (BSMMU) from July 2016 to July 2017. The mean age of the patients was 54 years, Male female ratio was 1.5:1 and most of the patients were farmers. After induction of 4 to 6 cycles of CTDa all patients were followed up at 6th and 12th weeks. At follow up we evaluated improvement of weakness, bone pain, Hb%, ESR, monoclonal protein, ß2microglobulin, bone marrow plasma cells and serum calcium and albumin level. Adverse effects, such as peripheral neuropathy, thromboembolic events, hyperglycemia, constipation, rash, and somnolence were also assessed. Results: Among 25 patients, complete response achieved only 13 patients (52%), where 20% and 16% of patients belonged to partial or no response respectively. The death occurred in 2 cases (12%). Conclusion: CTDa is a gentle approach to treat an especially frail group of patients, since virtually all patients ultimately relapse. KYAMC Journal Vol. 11, No.-3, October 2020, Page 124-128

PTEN Gene Deletions in Patients with Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4889-4889
Author(s):  
Xiao Ying Qi ◽  
A. Keith Stewart ◽  
Hong Chang
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Progression Free Survival ◽  
Myeloma Cell ◽  
Suppressor Gene ◽  
High Dose Chemotherapy ◽  
Pten Gene ◽  
Allelic Loss ◽  
High Dose ◽  
13Q Deletion

Abstract PTEN, a tumor suppressor gene, negatively regulates the anti-apoptotic action of akt phosphorylation. Allelic loss or mutation of this gene has been detected in many solid tumors and more recently in human myeloma cell lines (HMCLs). Expression of PTEN has resulted in growth inhibition and apoptosis of a HMCL, suggesting that it may play a role in the pathogenesis of multiple myeloma (MM). However, the PTEN status in tumor cells from patients with MM has not been determined. Using a triple staining method combining staining for cytoplasmic light chains and fluorescence in situ hybridization (FISH) with chromosome 10-centromere and PTEN-gene specific probes, we analyzed clonal plasma cells from 71 patients with MM, 10 with plasma cell leukemia (PCL) and 10 HMCLs. Hemizygous PTEN deletions were detected in 4 of 71 (5.6%) MM patients, 2 of 10 (20%) PCLs, and 2 of 10 (20%) HMCLs. The percentages of clonal plasma cells containing PTEN deletions ranged from 21–90% (median, 56%). Three of the 4 patients with PTEN deletions were detected at diagnosis with stage III disease (Duire-Salmon) and 1 was detected at relapse. Two patients had IgG kappa, 1 IgG lambda and 1 free lambda light chain. To correlate the PTEN status with other known genetic abnormalities in MM, we investigated 4 MM and 2 PCLs with PTEN deletions using FISH for chromosome13q, p53 status, translocations t(11;14), t(4;14) and t(14;16). One MM had a 13q deletion, 1 PCL had a t(11;14), and the other PCL had a t(14;16), a 13q deletion and a p53 deletion. All 4 MM patients with hemizygous PTEN deletions received melphalan based high-dose chemotherapy and autologous stem cell support. Their median overall survival (OS) was 48.1months, and progression free survival (PFS) was 42.8 months as compared to patients without PTEN deletions (OS, not reached, PFS, 25.8 months) (p=0.51 for OS, p=0.67 for PFS). Our results indicate that PTEN deletions are uncommon in MM patients and therefore unlikely represent a primary event for MM. PTEN deletions appear to occur in the advance stage of the disease, and are more frequently involved in PCL or HMCLs suggesting that deletions of PTEN may be associated with disease progression in a subset of MM.

Limited Feasibility of Double Transplant Program: A Multicenter Study on 151 Multiple Myeloma Patients Aged≤65 Years.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1175-1175
Author(s):  
A. Corso ◽  
S. Mangiacavalli ◽  
L. Barbarano ◽  
E. P. Alessandrino ◽  
R. Cairoli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
Stage Ii ◽  
High Dose ◽  
Severe Toxicity ◽  
Peripheral Blood Stem Cells ◽  
Free Survival ◽  
Intention To Treat ◽  
Transplant Program ◽  
Related Mortality

Abstract High dose therapy represents the gold standard therapy for newly diagnosed multiple myeloma (MM) patients (pts), with no definite agreement about the adoption of single or double transplant. From January 2000 to December 2004, 151 consecutive MM pts aged ≤65 years in stage II, III or I in progression according to Durie-Salmon were enrolled in a multicenter no randomised high dose program including a tandem transplant (Tx1; Tx2). The protocol was designed as follows: 2 pulse-VAD as induction, 2 DCEP to mobilise peripheral blood stem cells (PBSC), double auto-transplant 3-6 months apart each conditioned with high-dose Melphalan at the dose of 200 mg/m2. Patients characteristics at the enrolment: males 76 (51%), females 75 (49%), median age 55 (range: 35–65), stage I in progression 26 (17%), stage II 25 (16%), stage III 100 (67%). Response rates after each phase for the evaluable patients are reported in the table below VAD (151 pts) DCEP (146 pts) Tx1 (119 pts) Tx2 (63 pts) CR (%) 4 9 18 29 VGPR (%) 28 35 48 60 PR (%) 44 30 25 9 SD (%) 18 10 2 0 Progr (%) 6 16 7 0 Patients not addressed to transplant for mobilization failure were only 5%. Most of the patients (75%) collected ≥ 4x106CD34+cells/Kg after each DCEP-cycle which were considered adequate to rescue hemopoiesis after each transplant. The whole protocol was well-tolerated. In particular, no therapy related mortality was associated to pulse-VAD, or DCEP, and no difference between Tx1 and Tx2 as far the transplant related mortality was registered (1.5% after each transplant). Second transplant was not performed in 48 pts for the following reasons: 8 pts (7%) did not collect enough PBSC, 8 pts (7%) have had severe toxicity with the first transplant; 8 pts (7%) underwent allo-TMO; 7 pts (6%) had progressive disease and 15 pts (12%) refused Tx2. Finally only 76 pts (50% of the enrolled pts) completed the program with the second transplant. Analysing data on an intention-to-treat basis, median follow-up was 30 months, median Progression Free Survival (PFS) was 31 months, median overall survival (OS) was not reached. The median Event Free Survival (calculated from the completion of Tx1 to progression or any other event) was 20 months. No difference in terms of PFS and EFS was found comparing pts who finally received only Tx1, with those who completed the protocol (p=0.9; p=0.5). The EFS was not statistically different for patients receiving one or two transplant even when the analysis was performed according to the type of response achieved after Tx1. In conclusion, despite higher percentage of good quality responses (CR+VGPR) can be obtained with 2 transplants with respect to 1 (66% vs 89%) without additional toxicity, no difference in terms of PFS or EFS were observed between the patients who underwent 1 or 2 transplants. Thus, keeping into account the more complex management of patients in a tandem transplant program, it might be more advantageous to perform as initial therapeutic approach, high-dose protocol including only 1 transplant procedure.

New Criteria To Identify Risk of Progression in Monoclonal Gammopathy of Uncertain Significance: Multiparametric Flow Cytometry Analysis of Bone Marrow Plasma Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3517-3517
Author(s):  
Ernesto Perez-Persona ◽  
María-Belén Vidriales ◽  
Gema Mateo ◽  
Ramón Garcia Sanz ◽  
Marivi Mateos ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Flow Cytometry Analysis ◽  
Dna Index ◽  
Multiparametric Flow Cytometry ◽  
Uncertain Significance ◽  
Risk Of Progression ◽  
Bone Marrow Plasma

Abstract Monoclonal Gammopathy of Uncertain Significance (MGUS) is a monoclonal disorder defined by the presence of a serum monoclonal protein <3g/dL, bone marrow plasma cells < 10% and absence of end-organ damage. The risk of progression to multiple myeloma (MM) is about 1% per year, and therefore these patients require long follow-up. Accordingly, the definition of new parameters that could be used for the identification of patients at risk of progression could be of great value. The aim of the present study is to evaluate the utility of multiparameter flow cytometry analysis of bone marrow (BM) plasma cells (PC) for predicting the risk of progression of MGUS patients. From January 1996 to September 2004, bone marrow aspirate samples from 350 patients, who fulfil the criteria of MGUS according to the International Myeloma Working Group criteria, were analysed by multiparametric flow cytometry. A specific gate on PC was performed based on CD138/CD38 expression and FSC/SSC characteristics and PC were immunophenotypically classified as normal (polyclonal) or aberrant (clonal) according to the expression of CD138, CD38, CD45, CD19 and CD56 antigens. Twenty seven patients (8 %) progressed to MM, with a median time to progression (TTP) of 46 months (range 9 to 109 months). Interestingly, the percentage of aberrant PC within the total BM PC compartment (aPC/BMPCc) clearly identify patients at different risk of progression. Thus, TTP in patients with ≥ 95% aPC/BMPCc was 85 months vs not reached cases with <95% aPC/BMPCc (p=0.0000). Other parameters with a significant influence on progression in the univariate analysis were: paraprotein level (higher vs lower of 2 mg/dl; p= 0.0004), the presence of immunoparesis (no paresis vs. decreased levels in one or two Ig. p= 0.0005), Bence-Jones proteinuria (p= 0.0003), PC BM infiltration assessed both by morphology and flow cytometry (p=0.0074; and p= 0.001, respectively), and DNA index assessed by flow cytometry (diploid vs aneuploid; p=0.0064). Moreover, the cut off level of 95% aPC/BMPCc, also allows the discrimination of two risk categories upon considering only patients at low risk of progression, based on a low paraprotein level or absence of inmunoparesis (p= 0.0000 and p= 0.0000, respectively). On multivariate analysis only the percentage of aPC/BMPCc (≥95%) (p=0.000), the DNA index (p=0.007), and the Bence-Jones proteinuria (p=0.000) showed independent prognostic value. In summary, our results show that multiparameter FC evaluation of BMPC at diagnosis is a simple, cost-effective and valuable tool for predicting the risk of progression of MGUS patients.

Characteristics Of Multiple Myeloma Patients With 6-Year Or Longer Progression-Free Survival After a Single Autologous Transplant

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3366-3366 ◽  
Author(s):  
Kehinde U.A. Adekola ◽  
Qaiser Bashir ◽  
Nina Shah ◽  
Sai Ravi Pingali ◽  
Simrit Parmar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Progression Free Survival ◽  
High Dose ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Free Survival ◽  
Autologous Transplant ◽  
Preparative Regimen

Background High dose chemotherapy followed by an autologous stem cell transplant (auto-HCT) is considered standard of care in patients with newly diagnosed multiple myeloma (MM). In a recent randomized trial, median progression free survival (PFS) after auto-HCT, with or without maintenance therapy was 46 and 27 months, respectively (McCarthy P et al. NEJM 2012). However, about 15% of patients are reported to have much longer PFS (Pineda-Roman M et al. Cancer 2008). Here we tried to identify the factors that may predict a long PFS after auto-HCT. Methods We performed a retrospective chart review of patients who received an auto-HCT for MM between January 2000 and March 2007. A total of 1135 patients underwent an auto-HCT during this period, and 194 patients (17%) had a minimum PFS of 72 months or longer after a single auto-HCT. The primary objective was to determine the variables associated with a long PFS and overall survival (OS). Results Patient characteristics and outcomes are shown in the attached Table. The median age at auto-HCT was 56 years, and the median time from diagnosis to auto-HCT was 7.5 months. Twenty-three (13%) patients had ≥ 10% plasma cells in the bone marrow at auto-HCT and only 9 patients (4.8%) had high-risk cytogenetic abnormalities. One-hundred and fifty (77%) patients received induction therapy containing either an immunomodulatory (IMiD) agent or a proteasome inhibitor (PI). At the time of the auto-HSCT, only 13 (6.7%) patients were in CR and 38 (19.6%) were CR or VGPR after induction therapy (Table). One-hundred and sixty three (84%) patients received mephalan alone as conditioning regimen. Eighty-one (42%) patients received post auto-HCT maintenance. Eighty (41%) patients achieved a CR, while 104 (54%) achieved CR + VGPR after auto-HCT. Six patients (3.1%) developed a second primary malignancy post- autologous transplant. After a median follow-up of 95.4 months, median PFS was 97.3 months and median OS has not been reached. The 10-year PFS and OS were 41% and 73% respectively. Use of melphalan alone as preparative regimen was associated with a longer PFS and OS (p=0.004 and 0.004, respectively). Achievement of CR after auto-HCT was associated with a longer PFS only (p=0.001), and the use of IMiD or a PI as induction was associated with a longer OS (p=0.01). Conclusion Approximately 17% patients achieved a median PFS of 6 years or longer after a single auto-HCT. The long PFS in this cohort may be associated with younger age, low incidence of HR cytogenetics, use of an IMiD or PI as induction therapy, relatively low disease burden at auto-HCT, transplant from the year 2000 onwards, achievement of CR in >40% and the use of melphalan alone as preparative regimen. Disclosures: Shah: Celgene: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Qazilbash:Celgene: Membership on an entity’s Board of Directors or advisory committees.

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