Association of Immune Marker Changes With Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma

Ola Landgren, Jonathan N. Hofmann, Charlene McShane, Loredana Santo, Neha Korde, Malin Hultcrantz, Sham Mailankody, Dickran Kazandjian, Kazunori Murata, Katie Thoren, Lakshmi Ramanathan, Ahmet Dogan, Even Rustad, Sydney X. Lu, Theresia Akhlaghi, Sigurdur Y. Kristinsson, Magnus Björkholm, Sean Devlin, Mark P. Purdue, Ruth M. Pfeiffer & 1 others Ingemar Turesson

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Importance Multiple myeloma is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). Risk models that estimate the risk of progression from MGUS to multiple myeloma use data from a single time point, usually the initial workup. Objective To longitudinally investigate the alterations of serum immune markers with stable vs progressive MGUS. Design, Setting, and Participants This prospective cross-sectional cohort study included 77 469 adult participants aged 55 to 74 years in the screening arm of the National Cancer Institute Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had a diagnosis of progressing MGUS (n = 187) or stable MGUS (n = 498), including light-chain subtype, from November 1993, through December 2011. For each participant, all available serially stored prediagnostic serum samples (N = 3266) were obtained. Data analysis was performed from April 2018, to December 2018. Main Outcomes and Measures Serum protein and monoclonal immunoglobulin levels, serum free light chains, and serum light chains within each immunoglobulin class were measured. Results Of 685 individuals included in the study, 461 (67.3%) were men; the mean (SD) age was 69.1 (5.6) years. In cross-sectional modeling, risk factors associated with progressive MGUS were IgA isotype (adjusted odds ratio [OR], 1.80; 95% CI, 1.03-3.13; P = .04), 15 g/L or more monoclonal spike (adjusted OR, 23.5; 95% CI, 8.9-61.9; P < .001), skewed (<0.1 or >10) serum free light chains ratio (adjusted OR, 46.4; 95% CI, 18.4-117.0; P < .001), and severe immunoparesis (≥2 suppressed uninvolved immunoglobulins) (adjusted OR, 19.1; 95% Cl, 7.5-48.3; P < .001). Risk factors associated with progressive light-chain MGUS were skewed serum free light chains ratio (adjusted OR, 44.0; 95% CI, 14.2-136.3; P < .001) and severe immunoparesis (adjusted OR, 48.6; 95% CI, 9.5-248.2; P < .001). In longitudinal analysis of participants with serial samples prior to progression, 23 of 43 participants (53%) had high-risk MGUS before progression; 16 of these 23 (70%) experienced conversion from low-risk or intermediate-risk MGUS within 5 years. Similar results were found for light-chain MGUS.
LanguageEnglish
JournalJAMA Oncol
Early online date18 Jul 2019
DOIs
Publication statusEarly online date - 18 Jul 2019

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Monoclonal Gammopathy of Undetermined Significance
Multiple Myeloma
Biomarkers
Light
Odds Ratio
Serum
Immunoglobulins
Prostatic Neoplasms
National Cancer Institute (U.S.)
Immunoglobulin Isotypes
Early Detection of Cancer
Ovarian Neoplasms
Immunoglobulin A
Blood Proteins
Colorectal Neoplasms
Lung Neoplasms
Cohort Studies
Cross-Sectional Studies
Outcome Assessment (Health Care)

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Landgren, Ola ; Hofmann, Jonathan N. ; McShane, Charlene ; Santo, Loredana ; Korde, Neha ; Hultcrantz, Malin ; Mailankody, Sham ; Kazandjian, Dickran ; Murata, Kazunori ; Thoren, Katie ; Ramanathan, Lakshmi ; Dogan, Ahmet ; Rustad, Even ; Lu, Sydney X. ; Akhlaghi, Theresia ; Kristinsson, Sigurdur Y. ; Björkholm, Magnus ; Devlin, Sean ; Purdue, Mark P. ; Pfeiffer, Ruth M. ; Turesson, Ingemar. / Association of Immune Marker Changes With Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma. In: JAMA Oncol. 2019.
@article{ea9cedf37164408db5d68add8769af30,
title = "Association of Immune Marker Changes With Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma",
abstract = "Importance Multiple myeloma is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). Risk models that estimate the risk of progression from MGUS to multiple myeloma use data from a single time point, usually the initial workup. Objective To longitudinally investigate the alterations of serum immune markers with stable vs progressive MGUS. Design, Setting, and Participants This prospective cross-sectional cohort study included 77 469 adult participants aged 55 to 74 years in the screening arm of the National Cancer Institute Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had a diagnosis of progressing MGUS (n = 187) or stable MGUS (n = 498), including light-chain subtype, from November 1993, through December 2011. For each participant, all available serially stored prediagnostic serum samples (N = 3266) were obtained. Data analysis was performed from April 2018, to December 2018. Main Outcomes and Measures Serum protein and monoclonal immunoglobulin levels, serum free light chains, and serum light chains within each immunoglobulin class were measured. Results Of 685 individuals included in the study, 461 (67.3{\%}) were men; the mean (SD) age was 69.1 (5.6) years. In cross-sectional modeling, risk factors associated with progressive MGUS were IgA isotype (adjusted odds ratio [OR], 1.80; 95{\%} CI, 1.03-3.13; P = .04), 15 g/L or more monoclonal spike (adjusted OR, 23.5; 95{\%} CI, 8.9-61.9; P < .001), skewed (<0.1 or >10) serum free light chains ratio (adjusted OR, 46.4; 95{\%} CI, 18.4-117.0; P < .001), and severe immunoparesis (≥2 suppressed uninvolved immunoglobulins) (adjusted OR, 19.1; 95{\%} Cl, 7.5-48.3; P < .001). Risk factors associated with progressive light-chain MGUS were skewed serum free light chains ratio (adjusted OR, 44.0; 95{\%} CI, 14.2-136.3; P < .001) and severe immunoparesis (adjusted OR, 48.6; 95{\%} CI, 9.5-248.2; P < .001). In longitudinal analysis of participants with serial samples prior to progression, 23 of 43 participants (53{\%}) had high-risk MGUS before progression; 16 of these 23 (70{\%}) experienced conversion from low-risk or intermediate-risk MGUS within 5 years. Similar results were found for light-chain MGUS.",
author = "Ola Landgren and Hofmann, {Jonathan N.} and Charlene McShane and Loredana Santo and Neha Korde and Malin Hultcrantz and Sham Mailankody and Dickran Kazandjian and Kazunori Murata and Katie Thoren and Lakshmi Ramanathan and Ahmet Dogan and Even Rustad and Lu, {Sydney X.} and Theresia Akhlaghi and Kristinsson, {Sigurdur Y.} and Magnus Bj{\"o}rkholm and Sean Devlin and Purdue, {Mark P.} and Pfeiffer, {Ruth M.} and Ingemar Turesson",
year = "2019",
month = "7",
day = "18",
doi = "10.1001/jamaoncol.2019.1568",
language = "English",
journal = "JAMA oncology",
issn = "2374-2437",
publisher = "American Medical Association",

}

Landgren, O, Hofmann, JN, McShane, C, Santo, L, Korde, N, Hultcrantz, M, Mailankody, S, Kazandjian, D, Murata, K, Thoren, K, Ramanathan, L, Dogan, A, Rustad, E, Lu, SX, Akhlaghi, T, Kristinsson, SY, Björkholm, M, Devlin, S, Purdue, MP, Pfeiffer, RM & Turesson, I 2019, 'Association of Immune Marker Changes With Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma', JAMA Oncol. https://doi.org/10.1001/jamaoncol.2019.1568

Association of Immune Marker Changes With Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma. / Landgren, Ola; Hofmann, Jonathan N.; McShane, Charlene; Santo, Loredana; Korde, Neha ; Hultcrantz, Malin; Mailankody, Sham; Kazandjian, Dickran; Murata, Kazunori; Thoren, Katie; Ramanathan, Lakshmi; Dogan, Ahmet; Rustad, Even; Lu, Sydney X.; Akhlaghi, Theresia; Kristinsson, Sigurdur Y.; Björkholm, Magnus; Devlin, Sean ; Purdue, Mark P.; Pfeiffer, Ruth M.; Turesson, Ingemar.

In: JAMA Oncol, 18.07.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association of Immune Marker Changes With Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma

AU - Landgren, Ola

AU - Hofmann, Jonathan N.

AU - McShane, Charlene

AU - Santo, Loredana

AU - Korde, Neha

AU - Hultcrantz, Malin

AU - Mailankody, Sham

AU - Kazandjian, Dickran

AU - Murata, Kazunori

AU - Thoren, Katie

AU - Ramanathan, Lakshmi

AU - Dogan, Ahmet

AU - Rustad, Even

AU - Lu, Sydney X.

AU - Akhlaghi, Theresia

AU - Kristinsson, Sigurdur Y.

AU - Björkholm, Magnus

AU - Devlin, Sean

AU - Purdue, Mark P.

AU - Pfeiffer, Ruth M.

AU - Turesson, Ingemar

PY - 2019/7/18

Y1 - 2019/7/18

N2 - Importance Multiple myeloma is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). Risk models that estimate the risk of progression from MGUS to multiple myeloma use data from a single time point, usually the initial workup. Objective To longitudinally investigate the alterations of serum immune markers with stable vs progressive MGUS. Design, Setting, and Participants This prospective cross-sectional cohort study included 77 469 adult participants aged 55 to 74 years in the screening arm of the National Cancer Institute Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had a diagnosis of progressing MGUS (n = 187) or stable MGUS (n = 498), including light-chain subtype, from November 1993, through December 2011. For each participant, all available serially stored prediagnostic serum samples (N = 3266) were obtained. Data analysis was performed from April 2018, to December 2018. Main Outcomes and Measures Serum protein and monoclonal immunoglobulin levels, serum free light chains, and serum light chains within each immunoglobulin class were measured. Results Of 685 individuals included in the study, 461 (67.3%) were men; the mean (SD) age was 69.1 (5.6) years. In cross-sectional modeling, risk factors associated with progressive MGUS were IgA isotype (adjusted odds ratio [OR], 1.80; 95% CI, 1.03-3.13; P = .04), 15 g/L or more monoclonal spike (adjusted OR, 23.5; 95% CI, 8.9-61.9; P < .001), skewed (<0.1 or >10) serum free light chains ratio (adjusted OR, 46.4; 95% CI, 18.4-117.0; P < .001), and severe immunoparesis (≥2 suppressed uninvolved immunoglobulins) (adjusted OR, 19.1; 95% Cl, 7.5-48.3; P < .001). Risk factors associated with progressive light-chain MGUS were skewed serum free light chains ratio (adjusted OR, 44.0; 95% CI, 14.2-136.3; P < .001) and severe immunoparesis (adjusted OR, 48.6; 95% CI, 9.5-248.2; P < .001). In longitudinal analysis of participants with serial samples prior to progression, 23 of 43 participants (53%) had high-risk MGUS before progression; 16 of these 23 (70%) experienced conversion from low-risk or intermediate-risk MGUS within 5 years. Similar results were found for light-chain MGUS.

AB - Importance Multiple myeloma is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). Risk models that estimate the risk of progression from MGUS to multiple myeloma use data from a single time point, usually the initial workup. Objective To longitudinally investigate the alterations of serum immune markers with stable vs progressive MGUS. Design, Setting, and Participants This prospective cross-sectional cohort study included 77 469 adult participants aged 55 to 74 years in the screening arm of the National Cancer Institute Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had a diagnosis of progressing MGUS (n = 187) or stable MGUS (n = 498), including light-chain subtype, from November 1993, through December 2011. For each participant, all available serially stored prediagnostic serum samples (N = 3266) were obtained. Data analysis was performed from April 2018, to December 2018. Main Outcomes and Measures Serum protein and monoclonal immunoglobulin levels, serum free light chains, and serum light chains within each immunoglobulin class were measured. Results Of 685 individuals included in the study, 461 (67.3%) were men; the mean (SD) age was 69.1 (5.6) years. In cross-sectional modeling, risk factors associated with progressive MGUS were IgA isotype (adjusted odds ratio [OR], 1.80; 95% CI, 1.03-3.13; P = .04), 15 g/L or more monoclonal spike (adjusted OR, 23.5; 95% CI, 8.9-61.9; P < .001), skewed (<0.1 or >10) serum free light chains ratio (adjusted OR, 46.4; 95% CI, 18.4-117.0; P < .001), and severe immunoparesis (≥2 suppressed uninvolved immunoglobulins) (adjusted OR, 19.1; 95% Cl, 7.5-48.3; P < .001). Risk factors associated with progressive light-chain MGUS were skewed serum free light chains ratio (adjusted OR, 44.0; 95% CI, 14.2-136.3; P < .001) and severe immunoparesis (adjusted OR, 48.6; 95% CI, 9.5-248.2; P < .001). In longitudinal analysis of participants with serial samples prior to progression, 23 of 43 participants (53%) had high-risk MGUS before progression; 16 of these 23 (70%) experienced conversion from low-risk or intermediate-risk MGUS within 5 years. Similar results were found for light-chain MGUS.

U2 - 10.1001/jamaoncol.2019.1568

DO - 10.1001/jamaoncol.2019.1568

M3 - Article

JO - JAMA oncology

T2 - JAMA oncology

JF - JAMA oncology

SN - 2374-2437

ER -