Progression Risk Stratification of Asymptomatic Waldenström Macroglobulinemia.

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, β2-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.

• Authors: 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 Kyle, Steven P Treon, Jorge J Castillo, Meletios A Dimopoulos, Stephen M Ansell, Lorenzo Trippa, Irene M Ghobrial
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 37 Issue 16 Pg. 1403-1411 (06 01 2019) ISSN: 1527-7755 [Electronic] United States
• PMID: 30990729 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Validation Study)

Chemical References

• ALB protein, human
• Biomarkers
• Immunoglobulin M
• MYD88 protein, human
• Myeloid Differentiation Factor 88
• beta 2-Microglobulin
• Serum Albumin, Human

Topics

• Adult
• Aged
• Aged, 80 and over
• Asymptomatic Diseases
• Biomarkers (blood)
• Bone Marrow (pathology)
• Boston
• Decision Support Techniques
• Disease Progression
• Female
• Humans
• Immunoglobulin M (blood)
• Male
• Middle Aged
• Mutation
• Myeloid Differentiation Factor 88 (genetics)
• Predictive Value of Tests
• Prognosis
• Risk Assessment
• Risk Factors
• Serum Albumin, Human (metabolism)
• Time Factors
• Waldenstrom Macroglobulinemia (diagnosis, genetics, immunology, pathology)
• beta 2-Microglobulin (blood)