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Article ; Online: Treatment to suppression of focal lesions on positron emission tomography-computed tomography is a therapeutic goal in newly diagnosed multiple myeloma.

Davies, Faith E / Rosenthal, Adam / Rasche, Leo / Petty, Nathan M / McDonald, James E / Ntambi, James A / Steward, Doug M / Panozzo, Susan B / van Rhee, Frits / Zangari, Maurizio / Schinke, Carolina D / Thanendrarajan, Sharmilan / Walker, Brian / Weinhold, Niels / Barlogie, Bart / Hoering, Antje / Morgan, Gareth J

Haematologica

2018 Volume 103, Issue 6, Page(s) 1047–1053

Abstract: Fluorine-18 fluorodeoxyglucose positron emission tomography with computed tomography attenuation correction (PET-CT) in myeloma can detect and enumerate focal lesions by the quantitative characterization of metabolic activity. The aim of this study was ... ...

Abstract	Fluorine-18 fluorodeoxyglucose positron emission tomography with computed tomography attenuation correction (PET-CT) in myeloma can detect and enumerate focal lesions by the quantitative characterization of metabolic activity. The aim of this study was to determine the prognostic significance of the suppression of PET-CT activity at a number of time points post therapy initiation: day 7, post induction, post transplant, and at maintenance therapy. As part of the TT4-6 trial series, 596 patients underwent baseline PET-CT and were evaluated serially during their disease course using peak standardized uptake values above background red marrow signal. We demonstrate that the presence of more than 3 focal lesions at presentation identifies a group of patients with an adverse progression-free survival and overall survival. At day 7 of therapy, patients with complete focal lesion signal suppression revert to the same prognosis as those with no lesions at diagnosis. At later time points, the continued suppression of signal remains prognostically important. We conclude that for newly diagnosed patients with focal lesions, treatment until these lesions are suppressed is an important therapeutic goal as the prognosis of these patients is the same as those without lesions at diagnosis. (
MeSH term(s)	Aged ; Aged, 80 and over ; Combined Modality Therapy ; Female ; Fluorodeoxyglucose F18 ; Humans ; Male ; Middle Aged ; Multiple Myeloma/diagnosis ; Multiple Myeloma/mortality ; Multiple Myeloma/therapy ; Neoplasm, Residual/diagnosis ; Positron Emission Tomography Computed Tomography/methods ; Prognosis ; Survival Analysis ; Treatment Outcome
Chemical Substances	Fluorodeoxyglucose F18 (0Z5B2CJX4D)
Language	English
Publishing date	2018-03-22
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2017.177139
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Article: Assessment of Total Lesion Glycolysis by

McDonald, James E / Kessler, Marcus M / Gardner, Michael W / Buros, Amy F / Ntambi, James A / Waheed, Sarah / van Rhee, Frits / Zangari, Maurizio / Heuck, Christoph J / Petty, Nathan / Schinke, Carolina / Thanendrarajan, Sharmilan / Mitchell, Alan / Hoering, Antje / Barlogie, Bart / Morgan, Gareth J / Davies, Faith E

Clinical cancer research : an official journal of the American Association for Cancer Research

2017 Volume 23, Issue 8, Page(s) 1981–1987

Abstract: Purpose: ...

Abstract	Purpose:
MeSH term(s)	Aged ; Disease-Free Survival ; Female ; Fluorodeoxyglucose F18 ; Glycolysis ; Humans ; Image Interpretation, Computer-Assisted ; Imaging, Three-Dimensional ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multiple Myeloma/diagnostic imaging ; Multiple Myeloma/metabolism ; Multiple Myeloma/pathology ; Positron Emission Tomography Computed Tomography/methods ; Prognosis ; Radiopharmaceuticals
Chemical Substances	Radiopharmaceuticals ; Fluorodeoxyglucose F18 (0Z5B2CJX4D)
Language	English
Publishing date	2017--15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-16-0235
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Article: Fulminant onset of acute leukemia from normal hematopoiesis within 3 months of follow up for multiple myeloma treated with total therapy protocols.

Singh, Zeba N / Jethava, Yogesh / Post, Ginell R / Alapat, Daisy / Sawyer, Jeffrey / Waheed, Sarah / Nair, Bijay / Usmani, Saad Z / Bailey, Clyde / Petty, Nathan / Van Rhee, Frits / Barlogie, Bart

Clinical case reports

2015 Volume 3, Issue 3, Page(s) 183–192

Abstract: Assiduous surveillance for genetic aberrations is necessary in patients on cytotoxic therapies to detect therapy-related myeloid neoplasms (t-MN). Current modalities include metaphase cytogenetics and FISH. Since t-MN may develop abruptly in ... ...

Abstract	Assiduous surveillance for genetic aberrations is necessary in patients on cytotoxic therapies to detect therapy-related myeloid neoplasms (t-MN). Current modalities include metaphase cytogenetics and FISH. Since t-MN may develop abruptly in cytogenetically normal patients, a discussion exploring additional methods such as SNP-array and targeted-deep-sequencing to detect subchromosomal abnormalities is needed.
Language	English
Publishing date	2015-02-13
Publishing country	England
Document type	Case Reports
ZDB-ID	2740234-4
ISSN	2050-0904
ISSN	2050-0904
DOI	10.1002/ccr3.180
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Article ; Online: Bone marrow microenvironments that contribute to patient outcomes in newly diagnosed multiple myeloma: A cohort study of patients in the Total Therapy clinical trials.

Danziger, Samuel A / McConnell, Mark / Gockley, Jake / Young, Mary H / Rosenthal, Adam / Schmitz, Frank / Reiss, David J / Farmer, Phil / Alapat, Daisy V / Singh, Amrit / Ashby, Cody / Bauer, Michael / Ren, Yan / Smith, Kelsie / Couto, Suzana S / van Rhee, Frits / Davies, Faith / Zangari, Maurizio / Petty, Nathan /

Orlowski, Robert Z / Dhodapkar, Madhav V / Copeland, Wilbert B / Fox, Brian / Hoering, Antje / Fitch, Alison / Newhall, Katie / Barlogie, Bart / Trotter, Matthew W B / Hershberg, Robert M / Walker, Brian A / Dervan, Andrew P / Ratushny, Alexander V / Morgan, Gareth J

PLoS medicine

2020 Volume 17, Issue 11, Page(s) e1003323

Abstract: Background: The tumor microenvironment (TME) is increasingly appreciated as an important determinant of cancer outcome, including in multiple myeloma (MM). However, most myeloma microenvironment studies have been based on bone marrow (BM) aspirates, ... ...

Abstract	Background: The tumor microenvironment (TME) is increasingly appreciated as an important determinant of cancer outcome, including in multiple myeloma (MM). However, most myeloma microenvironment studies have been based on bone marrow (BM) aspirates, which often do not fully reflect the cellular content of BM tissue itself. To address this limitation in myeloma research, we systematically characterized the whole bone marrow (WBM) microenvironment during premalignant, baseline, on treatment, and post-treatment phases. Methods and findings: Between 2004 and 2019, 998 BM samples were taken from 436 patients with newly diagnosed MM (NDMM) at the University of Arkansas for Medical Sciences in Little Rock, Arkansas, United States of America. These patients were 61% male and 39% female, 89% White, 8% Black, and 3% other/refused, with a mean age of 58 years. Using WBM and matched cluster of differentiation (CD)138-selected tumor gene expression to control for tumor burden, we identified a subgroup of patients with an adverse TME associated with 17 fewer months of progression-free survival (PFS) (95% confidence interval [CI] 5-29, 49-69 versus 70-82 months, χ2 p = 0.001) and 15 fewer months of overall survival (OS; 95% CI -1 to 31, 92-120 versus 113-129 months, χ2 p = 0.036). Using immunohistochemistry-validated computational tools that identify distinct cell types from bulk gene expression, we showed that the adverse outcome was correlated with elevated CD8+ T cell and reduced granulocytic cell proportions. This microenvironment develops during the progression of premalignant to malignant disease and becomes less prevalent after therapy, in which it is associated with improved outcomes. In patients with quantified International Staging System (ISS) stage and 70-gene Prognostic Risk Score (GEP-70) scores, taking the microenvironment into consideration would have identified an additional 40 out of 290 patients (14%, premutation p = 0.001) with significantly worse outcomes (PFS, 95% CI 6-36, 49-73 versus 74-90 months) who were not identified by existing clinical (ISS stage III) and tumor (GEP-70) criteria as high risk. The main limitations of this study are that it relies on computationally identified cell types and that patients were treated with thalidomide rather than current therapies. Conclusions: In this study, we observe that granulocyte signatures in the MM TME contribute to a more accurate prognosis. This implies that future researchers and clinicians treating patients should quantify TME components, in particular monocytes and granulocytes, which are often ignored in microenvironment studies.
MeSH term(s)	Adult ; Bone Marrow/pathology ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma/diagnosis ; Multiple Myeloma/drug therapy ; Multiple Myeloma/pathology ; Prognosis ; Tumor Burden ; Tumor Microenvironment
Language	English
Publishing date	2020-11-04
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2185925-5
ISSN	1549-1676 ; 1549-1277
ISSN (online)	1549-1676
ISSN	1549-1277
DOI	10.1371/journal.pmed.1003323
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Article ; Online: Reiterative survival analyses of total therapy 2 for multiple myeloma elucidate follow-up time dependency of prognostic variables and treatment arms.

Barlogie, Bart / Anaissie, Elias / van Rhee, Frits / Shaughnessy, John D / Szymonifka, Jackie / Hoering, Antje / Petty, Nathan / Crowley, John

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2010 Volume 28, Issue 18, Page(s) 3023–3027

Abstract: Purpose: In Total Therapy 2, after randomly assigning 323 patients with myeloma to thalidomide and 345 to a control arm, no difference was observed in overall survival, with a median follow-up of 42 months, although at 72 months, survival was superior ... ...

Abstract	Purpose: In Total Therapy 2, after randomly assigning 323 patients with myeloma to thalidomide and 345 to a control arm, no difference was observed in overall survival, with a median follow-up of 42 months, although at 72 months, survival was superior on the thalidomide arm in the one third exhibiting cytogenetic abnormalities (CA). After further follow-up of 87 months, we examined, in reiterative analyses, the effect of increasing time intervals on clinical outcomes relevant to baseline prognostic variables and treatment randomization. Patients and methods: We investigated clinical trial end points as a function of increasing time intervals from protocol enrollment to determine consistencies of results by treatment and prognostic variables. Results: The complete congruence of serial survival plots for both study arms combined attested to stable patient characteristics over the time of accrual and the quality of follow-up management. Presence of CA was associated with consistently inferior survival curves from year 3 onward. Although 80% of patients randomly assigned to thalidomide discontinued study drug after 2 years because of toxicity, its clinical benefit did not reach statistical significance until year 10. The relative ranking order in multivariate models of prognostic factors remained stable over time. Decline in initially high hazard ratio values of gene array-defined high risk is consistent with an initial crisis phase that is time limited. Conclusion: Reporting potentially time-sensitive features as a part of clinical trial results will enable the critical reader to judge the robustness of prognostic factors and the time sensitivity of outcome predictors, with important implications for future trial designs.
MeSH term(s)	Angiogenesis Inhibitors/therapeutic use ; Follow-Up Studies ; Humans ; Multiple Myeloma/drug therapy ; Multiple Myeloma/mortality ; Multiple Myeloma/pathology ; Neoplasm Recurrence, Local/diagnosis ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Recurrence, Local/mortality ; Remission Induction ; Survival Rate ; Thalidomide/therapeutic use ; Time Factors ; Treatment Outcome
Chemical Substances	Angiogenesis Inhibitors ; Thalidomide (4Z8R6ORS6L)
Language	English
Publishing date	2010-05-17
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.2009.26.4465
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Article: Adverse Metaphase Cytogenetics Can Be Overcome by Adding Bortezomib and Thalidomide to Fractionated Melphalan Transplants.

Clinical cancer research : an official journal of the American Association for Cancer Research

2017 Volume 23, Issue 11, Page(s) 2665–2672

Abstract: Purpose: ...

Abstract	Purpose:
MeSH term(s)	Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Bortezomib/administration & dosage ; Bortezomib/adverse effects ; Chromosome Aberrations/drug effects ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Male ; Melphalan/administration & dosage ; Melphalan/adverse effects ; Metaphase/drug effects ; Middle Aged ; Multiple Myeloma/drug therapy ; Multiple Myeloma/genetics ; Multiple Myeloma/pathology ; Neoplasm Proteins/genetics ; Prognosis ; Prospective Studies ; Thalidomide/administration & dosage ; Thalidomide/adverse effects
Chemical Substances	Neoplasm Proteins ; Thalidomide (4Z8R6ORS6L) ; Bortezomib (69G8BD63PP) ; Melphalan (Q41OR9510P)
Language	English
Publishing date	2017-06-01
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-15-2620
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Article ; Online: Metronomic therapy is an effective salvage treatment for heavily pre-treated relapsed/refractory multiple myeloma.

Papanikolaou, Xenofon / Szymonifka, Jackie / Rosenthal, Adam / Heuck, Christoph J / Mitchell, Alan / Johann, Donald / Keller, Jason / Waheed, Sarah / Usmani, Saad Z / Van Rhee, Frits / Bailey, Clyde / Petty, Nathan / Hoering, Antje / Crowley, John / Barlogie, Bart

Haematologica

2013 Volume 98, Issue 7, Page(s) 1147–1153

Abstract: Relapsed/refractory multiple myeloma represents a major challenge in multiple myeloma therapy. For patients with relapsed/refractory multiple myeloma, we developed a treatment schema of metronomically scheduled drug therapy. We identified 186 patients ... ...

Abstract	Relapsed/refractory multiple myeloma represents a major challenge in multiple myeloma therapy. For patients with relapsed/refractory multiple myeloma, we developed a treatment schema of metronomically scheduled drug therapy. We identified 186 patients who had been treated with metronomic therapy between March 2004 and January 2012 with a median follow up of 24.2 months. Median age was 61 years (range 36-83). Median number of prior therapies was 14 (range 1-51). Median number of completed metronomic therapy cycles was 1 (range 1-5), while 45 of 186 (25%) received 2 or more cycles. Responses included complete remission in 11 of 186 patients (6%), very good partial remission in 12 of 186 (7%), partial remission in 65 of 179 (36%), and minimal response in 29 of 186 (16%), for an overall response rate of 63% (117 of 186). Median overall survival and progression-free survival were 11.2 and 3.6 months, respectively. Hematologic toxicity grading was problematic as 146 of 186 (78%) of patients presented with at least grade 2 thrombocytopenia within 90 days prior to starting metronomic therapy. Grade 4 leukopenia, anemia, and/or thrombocytopenia following metronomic therapy occurred in 108 of 186 (58%), 12 of 186 (6%), and 147 of 186 (79%) patients, respectively. Incidence of grade 3-4 neutropenic fever was 4 of 186 (2%). Most patients (177 of 186, 95%) were treated in an outpatient unit and secondary admissions due to regimen-related toxicity occurred in 37 of 186 (20%). Treatment-related mortality was evident in 2 of 186 (1%). In conclusion, metronomic therapy is an effective late salvage treatment in relapsed/refractory multiple myeloma, with a high overall response rate and a favorable toxicity profile.
MeSH term(s)	Administration, Metronomic ; Adult ; Aged ; Aged, 80 and over ; Cisplatin/administration & dosage ; Dexamethasone/administration & dosage ; Doxorubicin/administration & dosage ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Multiple Myeloma/drug therapy ; Multiple Myeloma/mortality ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Recurrence, Local/mortality ; Salvage Therapy/methods ; Survival Rate/trends ; Thalidomide/administration & dosage ; Treatment Outcome
Chemical Substances	Thalidomide (4Z8R6ORS6L) ; Dexamethasone (7S5I7G3JQL) ; Doxorubicin (80168379AG) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2013-05-28
Publishing country	Italy
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2013.085183
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Article ; Online: Four genes predict high risk of progression from smoldering to symptomatic multiple myeloma (SWOG S0120).

Khan, Rashid / Dhodapkar, Madhav / Rosenthal, Adam / Heuck, Christoph / Papanikolaou, Xenofon / Qu, Pingping / van Rhee, Frits / Zangari, Maurizio / Jethava, Yogesh / Epstein, Joshua / Yaccoby, Shmuel / Hoering, Antje / Crowley, John / Petty, Nathan / Bailey, Clyde / Morgan, Gareth / Barlogie, Bart

Haematologica

2015 Volume 100, Issue 9, Page(s) 1214–1221

Abstract: Multiple myeloma is preceded by an asymptomatic phase, comprising monoclonal gammopathy of uncertain significance and smoldering myeloma. Compared to the former, smoldering myeloma has a higher and non-uniform rate of progression to clinical myeloma, ... ...

Abstract	Multiple myeloma is preceded by an asymptomatic phase, comprising monoclonal gammopathy of uncertain significance and smoldering myeloma. Compared to the former, smoldering myeloma has a higher and non-uniform rate of progression to clinical myeloma, reflecting a subset of patients with higher risk. We evaluated the gene expression profile of smoldering myeloma plasma cells among 105 patients enrolled in a prospective observational trial at our institution, with a view to identifying a high-risk signature. Baseline clinical, bone marrow, cytogenetic and radiologic data were evaluated for their potential to predict time to therapy for symptomatic myeloma. A gene signature derived from four genes, at an optimal binary cut-point of 9.28, identified 14 patients (13%) with a 2-year therapy risk of 85.7%. Conversely, a low four-gene score (< 9.28) combined with baseline monoclonal protein < 3 g/dL and albumin ≥ 3.5 g/dL identified 61 patients with low-risk smoldering myeloma with a 5.0% chance of progression at 2 years. The top 40 probe sets showed concordance with indices of chromosome instability. These data demonstrate high discriminatory power of a gene-based assay and suggest a role for dysregulation of mitotic checkpoints in the context of genomic instability as a hallmark of high-risk smoldering myeloma.
MeSH term(s)	Aged ; Aged, 80 and over ; Bone Marrow/pathology ; Female ; Genes, Neoplasm ; Genomic Instability ; Humans ; Male ; Multiple Myeloma/genetics ; Multiple Myeloma/pathology ; Neoplasm Proteins/genetics ; Prospective Studies
Chemical Substances	Neoplasm Proteins
Language	English
Publishing date	2015-09
Publishing country	Italy
Document type	Clinical Trial ; Journal Article ; Multicenter Study ; Observational Study
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2015.124651
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Article ; Online: Prognostic implications of serial 18-fluoro-deoxyglucose emission tomography in multiple myeloma treated with total therapy 3.

Usmani, Saad Z / Mitchell, Alan / Waheed, Sarah / Crowley, John / Hoering, Antje / Petty, Nathan / Brown, Tracy / Bartel, Twyla / Anaissie, Elias / van Rhee, Frits / Barlogie, Bart

Blood

2013 Volume 121, Issue 10, Page(s) 1819–1823

Abstract: Prognostic implications of 3 imaging tools, metastatic bone survey, magnetic resonance imaging, and positron emission tomography (PET), were evaluated in 2 consecutive Total Therapy 3 trials for newly diagnosed myeloma. Data including PET at baseline and ...

Abstract	Prognostic implications of 3 imaging tools, metastatic bone survey, magnetic resonance imaging, and positron emission tomography (PET), were evaluated in 2 consecutive Total Therapy 3 trials for newly diagnosed myeloma. Data including PET at baseline and on day 7 of induction as well as standard prognostic factors were available in 302 patients of whom 277 also had gene expression profiling (GEP)-derived risk information. According to multivariate analysis, more than 3 focal lesions on day 7 imparted inferior overall survival and progression-free survival, overall and in the subset with GEP-risk data. GEP high-risk designation retained independent significance for all 3 end points examined. Thus, the presence of > 3 focal lesions on day 7 PET follow-up may be exploited toward early therapy change, especially for the 15% of patients with GEP-defined high-risk disease with a median overall survival expectation of 2 years. This trial was registered at www.clinicaltrials.gov as #NCT00081939 and # NCT00572169.
MeSH term(s)	Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/analysis ; Bone Neoplasms/drug therapy ; Bone Neoplasms/mortality ; Bone Neoplasms/secondary ; Clinical Trials as Topic ; Fluorodeoxyglucose F18 ; Follow-Up Studies ; Gene Expression Profiling ; Humans ; Magnetic Resonance Imaging ; Multiple Myeloma/drug therapy ; Multiple Myeloma/mortality ; Multiple Myeloma/pathology ; Multivariate Analysis ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Recurrence, Local/mortality ; Neoplasm Recurrence, Local/pathology ; Positron-Emission Tomography ; Prognosis ; Radiopharmaceuticals ; Survival Rate
Chemical Substances	Biomarkers, Tumor ; Radiopharmaceuticals ; Fluorodeoxyglucose F18 (0Z5B2CJX4D)
Language	English
Publishing date	2013-01-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2012-08-451690
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Article ; Online: Clinical, genomic, and imaging predictors of myeloma progression from asymptomatic monoclonal gammopathies (SWOG S0120).

Dhodapkar, Madhav V / Sexton, Rachael / Waheed, Sarah / Usmani, Saad / Papanikolaou, Xenofon / Nair, Bijay / Petty, Nathan / Shaughnessy, John D / Hoering, Antje / Crowley, John / Orlowski, Robert Z / Barlogie, Bart

Blood

2013 Volume 123, Issue 1, Page(s) 78–85

Abstract: All cases of clinical myeloma (CMM) are preceded by an asymptomatic monoclonal gammopathy (AMG), classified as either monoclonal gammopathy of undetermined significance (MGUS) or asymptomatic multiple myeloma (AMM). We analyzed data from AMG patients (n = ...

Abstract	All cases of clinical myeloma (CMM) are preceded by an asymptomatic monoclonal gammopathy (AMG), classified as either monoclonal gammopathy of undetermined significance (MGUS) or asymptomatic multiple myeloma (AMM). We analyzed data from AMG patients (n = 331) enrolled in a prospective, observational clinical trial (S0120). Baseline data from clinical variables, gene expression profiles (GEP) of purified tumor cells, and findings of magnetic resonance imaging (MRI) were correlated with the risk of progression to CMM requiring therapy. GEP of purified tumor cells revealed that all molecular subtypes of CMM are also represented in the AMG phase. An increased risk score (>-0.26) (based on a 70-gene signature, GEP70) was an independent predictor of the risk of progression to CMM. Combination of elevated serum free light chain, M-spike, and GEP70 risk score identified a subset with high risk (67% at 2 years) of progression to CMM requiring therapy. Importantly, absence of these factors in AMM patients predicted low risk similar to MGUS. Detection of multiple (>1) focal lesions by MRI also conferred an increased risk of progression. These data demonstrate that signatures associated with high-risk CMM impact disease risk and support inclusion of genomic analysis in the clinical management of AMGs.
MeSH term(s)	Aged ; Cohort Studies ; Disease Progression ; Female ; Humans ; Immunoglobulin Light Chains/blood ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Monoclonal Gammopathy of Undetermined Significance/diagnosis ; Monoclonal Gammopathy of Undetermined Significance/genetics ; Monoclonal Gammopathy of Undetermined Significance/therapy ; Multiple Myeloma/diagnosis ; Multiple Myeloma/genetics ; Multiple Myeloma/therapy ; Precancerous Conditions/diagnosis ; Precancerous Conditions/genetics ; Precancerous Conditions/therapy ; Proportional Hazards Models ; Prospective Studies ; Risk ; Syndecan-1/metabolism ; Time Factors
Chemical Substances	Immunoglobulin Light Chains ; Syndecan-1
Language	English
Publishing date	2013-10-21
Publishing country	United States
Document type	Journal Article ; Observational Study ; Research Support, N.I.H., Extramural
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2013-07-515239
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