Peripheral blood monoclonal plasma cells as a predictor of survival in patients with multiple myeloma [see comments]

The purpose of this study was to quantitate the number and labeling index of monoclonal plasma cells in the blood of patients with newly diagnosed multiple myeloma (MM) to learn if these values were independent prognostic factors for survival. Patients were candidates for this study if they had untreated myeloma requiring therapy, were evaluated at our institution between 1984 and 1993, and had a sample of blood analyzed with a sensitive immunofluorescence technique for monoclonal plasma cells and the blood B-cell labelling index (BLI). The % blood monoclonal plasma cells (%BPC) and the BLI were analyzed along with stage, marrow plasma cell LI, % marrow plasma cells, calcium, creatinine, albumin, beta-2-microglobulin, and C-reactive protein as univariate and multivariate factors for survival. Eighty percent of the 254 patients accrued to this study had monoclonal BPC detected. The median % BPC was 6% and 57% (144 of 254) of patients had a high number (> or = 4%). Patients with > or = 4% BPC had a median survival of 2.4 years vs 4.4 years for those with < 4% BPC (P < .001). The BLI was also prognostic (P = .008). In a multivariate analysis, the % BPC, age, albumin, stage, marrow plasma cell LI, and the BLI were independent factors for survival. The %BPC and the marrow plasma cell LI best separated the group into low, intermediate, and high risk myeloma with median survivals of 52, 35, and 26 months, respectively. Patients with high %BPC were less likely to have lytic bone disease from their MM (P = .002). The %BPC and the BLI are independent prognostic factors for survival and are useful in identifying patients as low, intermediate, and high risk. Clonal cells in the blood should be quantified in future clinical trials for myeloma.

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Peripheral blood monoclonal plasma cells as a predictor of survival in patients with multiple myeloma [see comments]

Blood ◽

10.1182/blood.v88.5.1780.1780 ◽

1996 ◽

Vol 88 (5) ◽

pp. 1780-1787 ◽

Cited By ~ 85

Author(s):

TE Witzig ◽

MA Gertz ◽

JA Lust ◽

RA Kyle ◽

WM O'Fallon ◽

...

Keyword(s):

Multiple Myeloma ◽

Prognostic Factors ◽

High Risk ◽

Plasma Cell ◽

Plasma Cells ◽

Cell Labelling ◽

Newly Diagnosed ◽

C Reactive Protein ◽

Reactive Protein ◽

Beta 2 Microglobulin

Abstract The purpose of this study was to quantitate the number and labeling index of monoclonal plasma cells in the blood of patients with newly diagnosed multiple myeloma (MM) to learn if these values were independent prognostic factors for survival. Patients were candidates for this study if they had untreated myeloma requiring therapy, were evaluated at our institution between 1984 and 1993, and had a sample of blood analyzed with a sensitive immunofluorescence technique for monoclonal plasma cells and the blood B-cell labelling index (BLI). The % blood monoclonal plasma cells (%BPC) and the BLI were analyzed along with stage, marrow plasma cell LI, % marrow plasma cells, calcium, creatinine, albumin, beta-2-microglobulin, and C-reactive protein as univariate and multivariate factors for survival. Eighty percent of the 254 patients accrued to this study had monoclonal BPC detected. The median % BPC was 6% and 57% (144 of 254) of patients had a high number (> or = 4%). Patients with > or = 4% BPC had a median survival of 2.4 years vs 4.4 years for those with < 4% BPC (P < .001). The BLI was also prognostic (P = .008). In a multivariate analysis, the % BPC, age, albumin, stage, marrow plasma cell LI, and the BLI were independent factors for survival. The %BPC and the marrow plasma cell LI best separated the group into low, intermediate, and high risk myeloma with median survivals of 52, 35, and 26 months, respectively. Patients with high %BPC were less likely to have lytic bone disease from their MM (P = .002). The %BPC and the BLI are independent prognostic factors for survival and are useful in identifying patients as low, intermediate, and high risk. Clonal cells in the blood should be quantified in future clinical trials for myeloma.

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Plasma cell labeling index and beta 2-microglobulin predict survival independent of thymidine kinase and C-reactive protein in multiple myeloma [see comments]

Blood ◽

10.1182/blood.v81.12.3382.bloodjournal81123382 ◽

1993 ◽

Vol 81 (12) ◽

pp. 3382-3387 ◽

Cited By ~ 3

Author(s):

PR Greipp ◽

JA Lust ◽

WM O'Fallon ◽

JA Katzmann ◽

TE Witzig ◽

...

Keyword(s):

Multiple Myeloma ◽

Prognostic Factors ◽

Thymidine Kinase ◽

Prognostic Significance ◽

Cell Labeling ◽

C Reactive Protein ◽

Prognostic Information ◽

Reactive Protein ◽

Beta 2 ◽

Beta 2 Microglobulin

The plasma cell labeling index (PCLI) and serum beta 2-microglobulin (beta 2M) are independent prognostic factors in multiple myeloma (MM). Recently, levels of thymidine kinase (TK) and C-reactive protein (CRP) have been shown to have prognostic value. We studied 107 patients with newly diagnosed myeloma to determine whether TK and CRP values added prognostic information not already available using the PCLI and beta 2M. Univariate survival analysis showed prognostic significance for the PCLI, TK, beta 2M, age, serum albumin, and CRP. Multivariate analysis showed that only PCLI and beta 2M have independent prognostic significance. The survival curves were better separated using the PCLI and beta 2M than with other combinations of variables. Among nine patients under age 65 with low PCLI and low beta 2M, eight were alive almost 6 years after starting chemotherapy. These good-risk patients could not be identified by standard clinical features. Although creatinine and calcium were normal, other features such as bone lesions, osteoporosis, fracture, and anemia were present and stage distribution was similar to other patients in the study. In conclusion, PCLI and beta 2M measured at diagnosis are independent prognostic factors. They must be considered when interpreting the results of clinical trials and should be helpful in counseling patients and in designing new trials. When the PCLI and beta 2M values are known, the TK and CRP values do not add useful additional prognostic information.

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Circulating plasma cells detected by flow cytometry as a predictor of survival in 302 patients with newly diagnosed multiple myeloma

Blood ◽

10.1182/blood-2005-05-1858 ◽

2005 ◽

Vol 106 (7) ◽

pp. 2276-2279 ◽

Cited By ~ 141

Author(s):

Grzegorz S. Nowakowski ◽

Thomas E. Witzig ◽

David Dingli ◽

Michal J. Tracz ◽

Morie A. Gertz ◽

...

Keyword(s):

Multiple Myeloma ◽

Flow Cytometry ◽

Median Survival ◽

Median Overall Survival ◽

Mononuclear Cells ◽

Plasma Cells ◽

Tumor Biology ◽

Newly Diagnosed ◽

C Reactive Protein ◽

Reactive Protein

Abstract We detected circulating plasma cells (PCs) by flow cytometry in 302 patients with newly diagnosed multiple myeloma (MM) by gating on CD38+CD45- cells. The number of circulating PCs per 50 000 mononuclear cells was reported. In 80 (27%) patients, no circulating PC were seen; 106 (35%) patients had 1 to 10 and 115 (38%) patients had more than 10 circulating PCs. Median overall survival for the 302 patients was 47 months. Patients with 10 or fewer circulating PCs had a median survival of 58.7 months, whereas patients with more than 10 circulating PCs had a median survival of 37.3 months (P = .001). On multivariate analysis, the prognostic value of circulating PCs was independent of β2-microglobulin, albumin, and C-reactive protein. There was only a weak correlation between tumor mass and circulating PCs, suggesting that the appearance of circulating PCs may be a reflection of tumor biology. We conclude that the number of circulating PCs measured by flow cytometry in patients with newly diagnosed MM is an independent predictor of survival.

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Plasma cell labeling index and beta 2-microglobulin predict survival independent of thymidine kinase and C-reactive protein in multiple myeloma [see comments]

Blood ◽

10.1182/blood.v81.12.3382.3382 ◽

1993 ◽

Vol 81 (12) ◽

pp. 3382-3387 ◽

Cited By ~ 230

Author(s):

PR Greipp ◽

JA Lust ◽

WM O'Fallon ◽

JA Katzmann ◽

TE Witzig ◽

...

Keyword(s):

Multiple Myeloma ◽

Prognostic Factors ◽

Thymidine Kinase ◽

Prognostic Significance ◽

Cell Labeling ◽

C Reactive Protein ◽

Prognostic Information ◽

Reactive Protein ◽

Beta 2 ◽

Beta 2 Microglobulin

Abstract The plasma cell labeling index (PCLI) and serum beta 2-microglobulin (beta 2M) are independent prognostic factors in multiple myeloma (MM). Recently, levels of thymidine kinase (TK) and C-reactive protein (CRP) have been shown to have prognostic value. We studied 107 patients with newly diagnosed myeloma to determine whether TK and CRP values added prognostic information not already available using the PCLI and beta 2M. Univariate survival analysis showed prognostic significance for the PCLI, TK, beta 2M, age, serum albumin, and CRP. Multivariate analysis showed that only PCLI and beta 2M have independent prognostic significance. The survival curves were better separated using the PCLI and beta 2M than with other combinations of variables. Among nine patients under age 65 with low PCLI and low beta 2M, eight were alive almost 6 years after starting chemotherapy. These good-risk patients could not be identified by standard clinical features. Although creatinine and calcium were normal, other features such as bone lesions, osteoporosis, fracture, and anemia were present and stage distribution was similar to other patients in the study. In conclusion, PCLI and beta 2M measured at diagnosis are independent prognostic factors. They must be considered when interpreting the results of clinical trials and should be helpful in counseling patients and in designing new trials. When the PCLI and beta 2M values are known, the TK and CRP values do not add useful additional prognostic information.

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MUKnine OPTIMUM protocol: a screening study to identify high-risk patients with multiple myeloma suitable for novel treatment approaches combined with a phase II study evaluating optimised combination of biological therapy in newly diagnosed high-risk multiple myeloma and plasma cell leukaemia

BMJ Open ◽

10.1136/bmjopen-2020-046225 ◽

2021 ◽

Vol 11 (3) ◽

pp. e046225

Author(s):

Sarah Brown ◽

Debbie Sherratt ◽

Samantha Hinsley ◽

Louise Flanagan ◽

Sadie Roberts ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Plasma Cell ◽

Phase Ii ◽

Whole Body ◽

Cell Leukaemia ◽

High Dose ◽

Newly Diagnosed ◽

Genetic Changes ◽

Novel Treatment

IntroductionMultiple myeloma (MM) is a plasma cell tumour with over 5800 new cases each year in the UK. The introduction of biological therapies has improved outcomes for the majority of patients with MM, but in approximately 20% of patients the tumour is characterised by genetic changes which confer a significantly poorer prognosis, generally termed high-risk (HR) MM. It is important to diagnose these genetic changes early and identify more effective first-line treatment options for these patients.Methods and analysisThe Myeloma UK nine OPTIMUM trial (MUKnine) evaluates novel treatment strategies for patients with HRMM. Patients with suspected or newly diagnosed MM, fit for intensive therapy, are offered participation in a tumour genetic screening protocol (MUKnine a), with primary endpoint proportion of patients with molecular screening performed within 8 weeks. Patients identified as molecularly HR are invited into the phase II, single-arm, multicentre trial (MUKnine b) investigating an intensive treatment schedule comprising bortezomib, lenalidomide, daratumumab, low-dose cyclophosphamide and dexamethasone, with single high-dose melphalan and autologous stem cell transplantation (ASCT) followed by combination consolidation and maintenance therapy. MUKnine b primary endpoints are minimal residual disease (MRD) at day 100 post-ASCT and progression-free survival. Secondary endpoints include response, safety and quality of life. The trial uses a Bayesian decision rule to determine if this treatment strategy is sufficiently active for further study. Patients identified as not having HR disease receive standard treatment and are followed up in a cohort study. Exploratory studies include longitudinal whole-body diffusion-weighted MRI for imaging MRD testing.Ethics and disseminationEthics approval London South East Research Ethics Committee (Ref: 17/LO/0022, 17/LO/0023). Results of studies will be submitted for publication in a peer-reviewed journal.Trial registration numberISRCTN16847817, May 2017; Pre-results.

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Genomic Basis of Multiple Myeloma Subtypes from the MMRF CoMMpass Study

10.1101/2021.08.02.21261211 ◽

2021 ◽

Author(s):

Sheri Skerget ◽

Daniel Penaherrera ◽

Ajai Chari ◽

Sundar Jagannath ◽

David S. Siegel ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Plasma Cells ◽

Hematological Malignancy ◽

Therapeutic Option ◽

Consensus Clustering ◽

Newly Diagnosed ◽

Loss Of Function ◽

Serial Samples ◽

Genomic Basis

Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The MMRF CoMMpass study is a longitudinal, observational clinical study of newly diagnosed multiple myeloma patients where tumor samples are characterized using whole genome, exome, and RNA sequencing at diagnosis and progression, and clinical data is collected every three months. Analyses of the baseline cohort identified genes that are the target of recurrent gain- and loss-of-function events. Consensus clustering identified 8 and 12 unique copy number and expression subtypes of myeloma, respectively, identifying high-risk genetic subtypes and elucidating many of the molecular underpinnings of these unique biological groups. Analysis of serial samples showed 25.5% of patients transition to a high-risk expression subtype at progression. We observed robust expression of immunotherapy targets in this subtype, suggesting a potential therapeutic option.

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Comparison of Newly Diagnosed and Relapsed Refractory Multiple Myeloma Using Transcriptional Profiling of Myeloma Cells.

Blood ◽

10.1182/blood.v106.11.1555.1555 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1555-1555

Author(s):

Shaji Kumar ◽

Philip R. Greipp ◽

Jessica L. Haug ◽

Michael Kline ◽

Wee Joo Chng ◽

...

Keyword(s):

Multiple Myeloma ◽

Drug Resistance ◽

Differential Expression ◽

Median Survival ◽

Plasma Cell ◽

Plasma Cells ◽

Expression Profiles ◽

Significant Proportion ◽

Newly Diagnosed ◽

Myeloma Cells

Abstract Background: Multiple myeloma (MM) is a plasma cell malignancy that is incurable with current approaches. The median survival for patients with MM is around four years and a significant proportion of patients experience a course characterized by multiple relapses treated with different therapies. The median survival for patients relapsing after the initial therapy is nearly 18 months and successive treatment strategies result in decreasing response durations, likely reflecting acquired drug resistance. In order to better understand the biological changes associated with advanced, relapsed, refractory MM, we compared gene expression profiles (GEP) of malignant plasma cells isolated from patients with relapsed refractory MM and compared them to plasma cells from patients with newly diagnosed MM. Methods: In order to obtain two relatively homogenous group of patients, we compared samples from 44 patient with newly diagnosed MM enrolled in the ECOG E1A00 clinical trial (comparing thalidomide and dexamethasone to dexamethasone alone) to 44 patients with relapsed refractory MM enrolled in a phase II trial of Velcade (SUMMIT), where most patients had four or more previous relapses. Plasma cells from bone marrow aspirates were separated by magnetic bead selection of CD138 positive cells and studied using Affymetrix HG-U133A chips using standard methodology. The arrays were analyzed using Genespring 7.2 software following GCRMA normalization and genes with differential expression between the two datasets were examined. Differentially expressed genes were further analyzed using Ingenuity Pathways Analysis program. Results: A total of 864 genes were identified which were at least two fold and significantly different between the newly diagnosed and relapsed patients. Using Ingenuity software, 437 of these genes were mapped to different biological networks. Examination of the canonical pathways demonstrated several important cellular pathways differentially regulated between the two groups. Several important mediators of the cytokines, receptors and respective signaling pathways appear to be down regulated in the relapsed group and included IGF-1, HGF, SDF-1 alpha, gp130 and importantly the MEK/ERK pathway. Additionally expression of adhesion molecules such as VCAM1 and PECAM was decreased in the relapsed group compared to newly diagnosed pts. There appear to increased tissue hypoxia in the relapsed marrow as indicated by up regulation of HIF-1 alpha as well increased levels of Placental growth factor. Myeloma cells from relapsed disease were characterized by decreased expression of mcl1, FLIP1, and bcl-xL and increased caspase 8 relative to newly diagnosed group. Also seen was decreased expression of the glucocorticoid and interferon receptors in the relapsed setting. Conclusion: Comparison of the GEP between MM cells from newly diagnosed and relapsed pts demonstrates important differences that have potential biological relevance. The plasma cell in the relapsed setting appears to be more independent of the tumor microenvironment. Additionally, differential expression of some of the genes provides clues to mechanisms of drug resistance commonly observed in the relapsed pts. We are in the process of validating some of the key findings from these analyses.

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Superior Rate of Complete Response with up-Front Velcade-Thalidomide-Dexamethasone Versus Thalidomide-Dexamethasone in Newly Diagnosed Multiple Myeloma Is Not Affected by Adverse Prognostic Factors, Including High-Risk Cytogenetic Abnormalities.

Blood ◽

10.1182/blood.v112.11.1662.1662 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1662-1662

Author(s):

Michele Cavo ◽

Nicoletta Testoni ◽

Carolina Terragna ◽

Giulia Marzocchi ◽

Sandra Durante ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Multivariate Analysis ◽

Prognostic Factors ◽

High Risk ◽

Light Chain ◽

Complete Response ◽

Phase Iii ◽

Newly Diagnosed ◽

Cox Regression Analysis

Abstract Complete response (CR) is an important objective of autologous stem-cell transplantation (ASCT) in multiple myeloma (MM). In comparison with conventional induction treatments, newer combinations of novel agents may effect increased rates of CR and near CR (nCR), a benefit potentially translating into even higher frequencies of CR/nCR after ASCT and improved clinical outcome. We designed a phase III study to detect an increase in CR+nCR rates from 10–15% with conventional Thalidomide-Dexamethasone (TD) to 20–30% with Velcade added to TD (VTD) in newly diagnosed MM. Both TD and VTD were given as three 21-day cycles in preparation for double ASCT. In the present analysis, CR+nCR rates by the two induction treatments were examined in relationship to baseline prognostic variables in 399 evaluable pts aged ≤65 years, of whom 199 randomized to VTD and 200 to TD. All analyses were intent to treat. In comparison with TD, VTD effected higher rates of CR+nCR (12% vs 33%, P<0.001) and of ≥very good partial response (VGPR) (30% vs 61%, P<0.001). By univariate analysis, superiority of VTD to TD was maintained across all sub-group analyses according to standard prognostic factors, including β2-m, albumin, stage (ISS), Hb, PLTs, bone marrow PC, M protein isotype, LDH, CRP. In particular, the rates of CR+nCR with VTD vs TD in pts with standard poor prognostic factors were as follows: ISS stage 3 (23.5% vs 6%, P=0.03), Hb<10 g/dL (24% vs 4%, P=0.002), PLTs<150.000/μL (35% vs 4%, P=0.009), bone marrow PC ≥50% (31% vs 13%, P<0.001), IgA isotype (63% vs 15%, P<0.001), LDH >190 U/L (33% vs 9%, P<0.001), CRP ≥8 mg/L (29% vs 10%, P=0.004). We next examined CR+nCRs by treatment arms in relationship to cytogenetics (FISH data available in 93% to 99% of all pts). Superior CR+nCR rates were effected by VTD vs TD in the presence of high-risk cytogenetics, including del(13) (39% vs 10%, P<0.001), t(4;14) (39.5% vs 10%, P=0.002), combined t(4;14) and del(13) (32% vs 0%, P=0.001), and del(17p) (28.5% vs 0%, P=0.03). Remarkably, when examined in the context of the VTD arm, high-quality response rates were significantly higher for pts carrying del(13) and t(4;14) vs those who lacked these abnormalities [del(13): CR+nCR:39% vs 24%, P=0.03; ≥VGPR: 71% vs 48%, P=0.001] [t(4;14): ≥VGPR:79% vs 55%, P=0.007)]. An opposite trend was noted for pts in the TD arm, whose probability to attain ≥VGPR was adversely affected by the presence of del(13) (P=0.07) and del(17p) (P=0.03). Variables associated with achievement of CR+nCR in the two arms that retained statistical significance when assessed by multivariate Cox regression analysis included randomization to VTD (P<0.001), light chain only subtype (P<0.001), IgA isotype (P<0.001) and Hb>10 g/dL (P=0.01). In the VTD arm, a positive correlation was observed with del(13) (P=0.006) and t(4;14) (P=0.02). Response to first ASCT with melphalan 200 mg/m2 could be evaluated in 297 pts, of whom 145 randomized to VTD and 152 to TD. Randomization to VTD was closely associated with increased CR+nCR rates (54% vs 29% with TD, P<0.001) and remained statistically significant (P<0.001) also in the multivariate analysis. Additional factors predicting for superior post-ASCT CR+nCR rates in the multivariate setting included light chain only subtype (P<0.001) and IgA isotype (P=0.005). We conclude that randomization to up-front VTD was the strongest and independent factor associated with increased rates of CR+nCR before ASCT. Superiority of VTD to TD pertained in both low-risk and high-risk sub-groups, including the traditionally unfavorable sub-groups carrying del(13), t(4,14) and del(17p). Remarkably, in the VTD arm improved postinduction CR+nCR rates were significantly associated with the presence of del(13) and t(4;14) in the multivariate analysis. Benefit from VTD vs TD as primary induction therapy translated into significantly improved CR+nCR rates after the first ASCT and remained statistically significant when assessed by multivariate analysis.

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Rising Plasma Cell Proliferation By Ki67/CD138 Ratio at Relapse Is a Marker of High Risk Disease in Multiple Myeloma

Blood ◽

10.1182/blood.v126.23.2991.2991 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2991-2991

Author(s):

Peter A. Forsberg ◽

Tomer M Mark ◽

Sujitha Yadlapati ◽

Adriana C Rossi ◽

Roger N Pearse ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Cell Proliferation ◽

Overall Survival ◽

High Risk ◽

Plasma Cell ◽

Plasma Cells ◽

Initial Therapy ◽

First Line ◽

High Risk Disease

Abstract Background: Assessment of malignant plasma cell cycling via plasma cell labeling index (PCLI) has been a validated prognostic tool in multiple myeloma (MM) for years but utilization remains limited. We recently developed a novel immunohistochemical (IHC) co-staining technique for CD138 and Ki67 expression to quantify plasma cells in active cycling. Previously presented results from newly diagnosed patients demonstrate that having an elevated ratio of plasma cells in active cycle by co-expression of CD138 and Ki67 (>5%) is associated with aggressive disease and poor outcomes including shorter overall survival (OS). The expansion of subclones with higher proliferative capacity following initial therapy may be an indicator of a higher risk relapse event and indicate poor prognosis. Here we assess MM patients (pts) with Ki67/CD138 co-staining on bone marrow samples both at diagnosis and relapse to assess the impact of changes in cell cycling ratio on outcomes with subsequent therapy and overall clinical course. Methods: A retrospective cohort study of pts with treated symptomatic MM was performed by interrogation of the clinical database at the Weill Cornell Medical College / New York Presbyterian Hospital (WCMC/NYPH). For inclusion in the analysis, pts must have had bone marrow evaluation with double-staining for Ki67 and CD138 by immunohistochemistry both at diagnosis and relapse. Pts must have completed their first line and relapse treatments at WCMC/NYPH. The Ki67% was calculated as the ratio of plasma cells expressing CD138 that were also found to express Ki67. Treatment outcomes were stratified and compared based on alterations in Ki67% between diagnosis and relapse. Results: We identified 37 pts with bone marrow sampling that was evaluated for CD138 and Ki67 co-expression both at diagnosis and at the time of relapse. These pts had undergone a median of 2 lines of prior treatment at the time of relapse bone marrow biopsy (range 1-7). 19 pts were identified to have a rising Ki67% between diagnosis and relapse defined at a 5% or greater increase, the other 18 pts had stable or decreased Ki67%. Pts with a rising Ki67% at relapse had a shorter OS with a median of 72 months vs not reached (p=0.0069), Figure 1. Pts who had rising Ki67% at relapse had shorter progression free survival (PFS) on first line treatment with a median of 25 vs 47 months (p=0.036), Figure 2. Additionally pts with rising Ki67% had a trend towards shorter PFS with the treatment they received after relapse with median of 12.5 vs 3.5 months (p=0.09). Relapse regimens were most commonly carfilzomib (n=9), pomalidomide (5) or ixazomib (4) based. 37% of pts (7/19) with rising Ki67% achieved PR or better on relapsed treatment vs 67% (12/18) with stable Ki67%. Discussion: The presence of clonal evolution and selection of higher risk clones under therapeutic pressure in multiple myeloma is a key feature of disease progression. The ability to improve risk stratification at the time of relapse may help guide clinical decision making to best suit individual patient needs. We have identified rising plasma cell proliferation through quantification of Ki67/CD138 co-expression at relapse to be a useful marker of high risk disease evolution. This appears to help identify the emergence of higher risk clones which are ultimately responsible for treatment resistant disease. Patients with rising Ki67% were more likely than patients with stable Ki67% to have early relapses to initial therapy, were less likely to achieve responses to relapse regimens or to maintain their response and had shorter overall survival. Further evaluation is needed to identify if different approaches to patients with increasing proliferation may improve outcomes in these patients. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Mark: Calgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Rossi:Calgene: Speakers Bureau. Pearse:Celegen: Consultancy. Pekle:Celgene: Speakers Bureau; Takeda: Speakers Bureau. Perry:Celgene: Speakers Bureau; Takeda: Speakers Bureau. Coleman:Celgene: Speakers Bureau; Takeda: Speakers Bureau. Niesvizky:Celgene: Consultancy, Speakers Bureau.

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PLP2 Expression as a Prognostic and Therapeutic Indicator in High-Risk Multiple Myeloma

BioMed Research International ◽

10.1155/2020/4286101 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Hua Bai ◽

Yudi Zhu ◽

Peipei Xu ◽

Bing Chen

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Poor Prognosis ◽

Proteolipid Protein ◽

Clinicopathological Features ◽

Newly Diagnosed ◽

Biopsy Specimens ◽

Prognostic Prediction ◽

Beta 2 Microglobulin ◽

High Beta

Multiple myeloma (MM) is a devastating cancer with a highly heterogeneous outcome. Because of the heterogeneity of myeloma cells, risk stratification is important for making therapeutic regimens. Nevertheless, no immunohistochemical predictive and prognostic marker has been constructed yet. In the present study, we explored the prognostic value of proteolipid protein 2 (PLP2) in MM patients using immunohistochemistry (IHC). We assessed PLP2 expression in bone marrow (BM) biopsy specimens obtained from 87 newly diagnosed MM (NDMM) patients. Correlations between PLP2 expression and clinicopathological features were analyzed. PLP2 expression was present in high-risk MM patients, which was increased with disease progression and poor prognosis. PLP2 was increasing in parallel with high beta-2 microglobulin (β2-MG) and lactate dehydrogenase (LDH). Furthermore, MM patients with low PLP2 expression could achieve a favorable treatment response. PLP2 may be a novel biomarker for prognostic prediction and a therapeutic target for anti-MM treatments.

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