Progression risk stratification of asymptomatic Waldenström macroglobulinemia

Mark Bustoros, Romanos Sklavenitis-Pistofidis, Prashant Kapoor, Chia Jen Liu, Efstathios Kastritis, Saurabh Zanwar, Geoffrey Fell, Jithma P. Abeykoon, Kalvis Hornburg, Carl Jannes Neuse, Catherine R. Marinac, David Liu, Jenny Soiffer, Maria Gavriatopoulou, Cody Boehner, Joseph M. Cappuccio, Henry Dumke, Kaitlen Reyes, Robert J. Soiffer, Robert A. KyleSteven P. Treon, Jorge J. Castillo, Meletios A. Dimopoulos, Stephen M. Ansell, Lorenzo Trippa, Irene M. Ghobrial

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Abstract

BACKGROUND Waldenström macroglobulinemia (WM) is preceded by asymptomatic WM (AWM), for which the risk of progression to overt disease is not well defined. METHODS We studied 439 patients with AWM, who were diagnosed and observed at Dana-Farber Cancer Institute between 1992 and 2014. RESULTS During the 23-year study period, with a median follow-up of 7.8 years, 317 patients progressed to symptomatic WM (72%). Immunoglobulin M 4,500 mg/dL or greater, bone marrow lymphoplasmacytic infiltration 70% or greater, b2-microglobulin 4.0 mg/dL or greater, and albumin 3.5 g/dL or less were all identified as independent predictors of disease progression. To assess progression risk in patients with AWM, we trained and cross-validated a proportional hazards model using bone marrow infiltration, immunoglobulin M, albumin, and beta-2 microglobulin values as continuous measures. The model divided the cohort into three distinct risk groups: a high-risk group with a median time to progression (TTP) of 1.8 years, an intermediate-risk group with a median TTP of 4.8 years, and a low-risk group with a median TTP of 9.3 years. We validated this model in two external cohorts, demonstrating robustness and generalizability. For clinical applicability, we made the model available as a Web page application (www.awmrisk.com). By combining two cohorts, we were powered to identify wild type MYD88 as an independent predictor of progression (hazard ratio, 2.7). CONCLUSION This classification system is positioned to inform patient monitoring and care and, for the first time to our knowledge, to identify patients with high-risk AWM who may need closer follow-up or benefit from early intervention.

Original languageEnglish (US)
Pages (from-to)1403-1411
Number of pages9
JournalJournal of Clinical Oncology
Volume37
Issue number16
DOIs
StatePublished - Jan 1 2019

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Waldenstrom Macroglobulinemia
Immunoglobulin M
Albumins
Bone Marrow
beta 2-Microglobulin
Physiologic Monitoring
Proportional Hazards Models
Disease Progression
Patient Care

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Bustoros, M., Sklavenitis-Pistofidis, R., Kapoor, P., Liu, C. J., Kastritis, E., Zanwar, S., ... Ghobrial, I. M. (2019). Progression risk stratification of asymptomatic Waldenström macroglobulinemia. Journal of Clinical Oncology, 37(16), 1403-1411. https://doi.org/10.1200/JCO.19.00394

Progression risk stratification of asymptomatic Waldenström macroglobulinemia. / Bustoros, Mark; Sklavenitis-Pistofidis, Romanos; Kapoor, Prashant; Liu, Chia Jen; Kastritis, Efstathios; Zanwar, Saurabh; Fell, Geoffrey; Abeykoon, Jithma P.; Hornburg, Kalvis; Neuse, Carl Jannes; Marinac, Catherine R.; Liu, David; Soiffer, Jenny; Gavriatopoulou, Maria; Boehner, Cody; Cappuccio, Joseph M.; Dumke, Henry; Reyes, Kaitlen; Soiffer, Robert J.; Kyle, Robert A.; Treon, Steven P.; Castillo, Jorge J.; Dimopoulos, Meletios A.; Ansell, Stephen M.; Trippa, Lorenzo; Ghobrial, Irene M.

In: Journal of Clinical Oncology, Vol. 37, No. 16, 01.01.2019, p. 1403-1411.

Research output: Contribution to journalArticle

Bustoros, M, Sklavenitis-Pistofidis, R, Kapoor, P, Liu, CJ, Kastritis, E, Zanwar, S, Fell, G, Abeykoon, JP, Hornburg, K, Neuse, CJ, Marinac, CR, Liu, D, Soiffer, J, Gavriatopoulou, M, Boehner, C, Cappuccio, JM, Dumke, H, Reyes, K, Soiffer, RJ, Kyle, RA, Treon, SP, Castillo, JJ, Dimopoulos, MA, Ansell, SM, Trippa, L & Ghobrial, IM 2019, 'Progression risk stratification of asymptomatic Waldenström macroglobulinemia', Journal of Clinical Oncology, vol. 37, no. 16, pp. 1403-1411. https://doi.org/10.1200/JCO.19.00394
Bustoros M, Sklavenitis-Pistofidis R, Kapoor P, Liu CJ, Kastritis E, Zanwar S et al. Progression risk stratification of asymptomatic Waldenström macroglobulinemia. Journal of Clinical Oncology. 2019 Jan 1;37(16):1403-1411. https://doi.org/10.1200/JCO.19.00394
Bustoros, Mark ; Sklavenitis-Pistofidis, Romanos ; Kapoor, Prashant ; Liu, Chia Jen ; Kastritis, Efstathios ; Zanwar, Saurabh ; Fell, Geoffrey ; Abeykoon, Jithma P. ; Hornburg, Kalvis ; Neuse, Carl Jannes ; Marinac, Catherine R. ; Liu, David ; Soiffer, Jenny ; Gavriatopoulou, Maria ; Boehner, Cody ; Cappuccio, Joseph M. ; Dumke, Henry ; Reyes, Kaitlen ; Soiffer, Robert J. ; Kyle, Robert A. ; Treon, Steven P. ; Castillo, Jorge J. ; Dimopoulos, Meletios A. ; Ansell, Stephen M. ; Trippa, Lorenzo ; Ghobrial, Irene M. / Progression risk stratification of asymptomatic Waldenström macroglobulinemia. In: Journal of Clinical Oncology. 2019 ; Vol. 37, No. 16. pp. 1403-1411.
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abstract = "BACKGROUND Waldenstr{\"o}m macroglobulinemia (WM) is preceded by asymptomatic WM (AWM), for which the risk of progression to overt disease is not well defined. METHODS We studied 439 patients with AWM, who were diagnosed and observed at Dana-Farber Cancer Institute between 1992 and 2014. RESULTS During the 23-year study period, with a median follow-up of 7.8 years, 317 patients progressed to symptomatic WM (72{\%}). Immunoglobulin M 4,500 mg/dL or greater, bone marrow lymphoplasmacytic infiltration 70{\%} or greater, b2-microglobulin 4.0 mg/dL or greater, and albumin 3.5 g/dL or less were all identified as independent predictors of disease progression. To assess progression risk in patients with AWM, we trained and cross-validated a proportional hazards model using bone marrow infiltration, immunoglobulin M, albumin, and beta-2 microglobulin values as continuous measures. The model divided the cohort into three distinct risk groups: a high-risk group with a median time to progression (TTP) of 1.8 years, an intermediate-risk group with a median TTP of 4.8 years, and a low-risk group with a median TTP of 9.3 years. We validated this model in two external cohorts, demonstrating robustness and generalizability. For clinical applicability, we made the model available as a Web page application (www.awmrisk.com). By combining two cohorts, we were powered to identify wild type MYD88 as an independent predictor of progression (hazard ratio, 2.7). CONCLUSION This classification system is positioned to inform patient monitoring and care and, for the first time to our knowledge, to identify patients with high-risk AWM who may need closer follow-up or benefit from early intervention.",
author = "Mark Bustoros and Romanos Sklavenitis-Pistofidis and Prashant Kapoor and Liu, {Chia Jen} and Efstathios Kastritis and Saurabh Zanwar and Geoffrey Fell and Abeykoon, {Jithma P.} and Kalvis Hornburg and Neuse, {Carl Jannes} and Marinac, {Catherine R.} and David Liu and Jenny Soiffer and Maria Gavriatopoulou and Cody Boehner and Cappuccio, {Joseph M.} and Henry Dumke and Kaitlen Reyes and Soiffer, {Robert J.} and Kyle, {Robert A.} and Treon, {Steven P.} and Castillo, {Jorge J.} and Dimopoulos, {Meletios A.} and Ansell, {Stephen M.} and Lorenzo Trippa and Ghobrial, {Irene M.}",
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T1 - Progression risk stratification of asymptomatic Waldenström macroglobulinemia

AU - Bustoros, Mark

AU - Sklavenitis-Pistofidis, Romanos

AU - Kapoor, Prashant

AU - Liu, Chia Jen

AU - Kastritis, Efstathios

AU - Zanwar, Saurabh

AU - Fell, Geoffrey

AU - Abeykoon, Jithma P.

AU - Hornburg, Kalvis

AU - Neuse, Carl Jannes

AU - Marinac, Catherine R.

AU - Liu, David

AU - Soiffer, Jenny

AU - Gavriatopoulou, Maria

AU - Boehner, Cody

AU - Cappuccio, Joseph M.

AU - Dumke, Henry

AU - Reyes, Kaitlen

AU - Soiffer, Robert J.

AU - Kyle, Robert A.

AU - Treon, Steven P.

AU - Castillo, Jorge J.

AU - Dimopoulos, Meletios A.

AU - Ansell, Stephen M.

AU - Trippa, Lorenzo

AU - Ghobrial, Irene M.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - BACKGROUND Waldenström macroglobulinemia (WM) is preceded by asymptomatic WM (AWM), for which the risk of progression to overt disease is not well defined. METHODS We studied 439 patients with AWM, who were diagnosed and observed at Dana-Farber Cancer Institute between 1992 and 2014. RESULTS During the 23-year study period, with a median follow-up of 7.8 years, 317 patients progressed to symptomatic WM (72%). Immunoglobulin M 4,500 mg/dL or greater, bone marrow lymphoplasmacytic infiltration 70% or greater, b2-microglobulin 4.0 mg/dL or greater, and albumin 3.5 g/dL or less were all identified as independent predictors of disease progression. To assess progression risk in patients with AWM, we trained and cross-validated a proportional hazards model using bone marrow infiltration, immunoglobulin M, albumin, and beta-2 microglobulin values as continuous measures. The model divided the cohort into three distinct risk groups: a high-risk group with a median time to progression (TTP) of 1.8 years, an intermediate-risk group with a median TTP of 4.8 years, and a low-risk group with a median TTP of 9.3 years. We validated this model in two external cohorts, demonstrating robustness and generalizability. For clinical applicability, we made the model available as a Web page application (www.awmrisk.com). By combining two cohorts, we were powered to identify wild type MYD88 as an independent predictor of progression (hazard ratio, 2.7). CONCLUSION This classification system is positioned to inform patient monitoring and care and, for the first time to our knowledge, to identify patients with high-risk AWM who may need closer follow-up or benefit from early intervention.

AB - BACKGROUND Waldenström macroglobulinemia (WM) is preceded by asymptomatic WM (AWM), for which the risk of progression to overt disease is not well defined. METHODS We studied 439 patients with AWM, who were diagnosed and observed at Dana-Farber Cancer Institute between 1992 and 2014. RESULTS During the 23-year study period, with a median follow-up of 7.8 years, 317 patients progressed to symptomatic WM (72%). Immunoglobulin M 4,500 mg/dL or greater, bone marrow lymphoplasmacytic infiltration 70% or greater, b2-microglobulin 4.0 mg/dL or greater, and albumin 3.5 g/dL or less were all identified as independent predictors of disease progression. To assess progression risk in patients with AWM, we trained and cross-validated a proportional hazards model using bone marrow infiltration, immunoglobulin M, albumin, and beta-2 microglobulin values as continuous measures. The model divided the cohort into three distinct risk groups: a high-risk group with a median time to progression (TTP) of 1.8 years, an intermediate-risk group with a median TTP of 4.8 years, and a low-risk group with a median TTP of 9.3 years. We validated this model in two external cohorts, demonstrating robustness and generalizability. For clinical applicability, we made the model available as a Web page application (www.awmrisk.com). By combining two cohorts, we were powered to identify wild type MYD88 as an independent predictor of progression (hazard ratio, 2.7). CONCLUSION This classification system is positioned to inform patient monitoring and care and, for the first time to our knowledge, to identify patients with high-risk AWM who may need closer follow-up or benefit from early intervention.

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