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Risk Model for Disease Progression in Asymptomatic Waldenström’s Macroglobulinemia

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Key Points

  • Levels of immunoglobulin M, bone marrow lymphoplasmacytic infiltration, β2-microglobulin, and albumin were significant independent predictors of disease progression.
  • A model using these factors as continuous variables distinguished groups at high, intermediate, and low risk of progression.

In a study reported in the Journal of Clinical Oncology, Bustoros et al developed a model for predicting risk of progression from asymptomatic Waldenström’s macroglobulinemia to symptomatic disease requiring treatment.

The study involved 439 patients with asymptomatic Waldenström’s macroglobulinemia who were diagnosed and followed at Dana-Farber Cancer Institute between 1992 and 2014. With a median follow-up of 7.8 years, 317 patients (72%) had disease progression to symptomatic Waldenström’s macroglobulinemia.

Risk Model

In multivariate analysis of risk factors for progression, immunoglobulin M ≥ 4,500 mg/dL (hazard ratio [HR] = 4.65), bone marrow lymphoplasmacytic infiltration ≥ 70% (HR = 2.56), β2-microglobulin ≥ 4.0 mg/dL (HR = 2.31), and albumin ≤ 3.5 g/dL (HR = 2.78) were significant independent predictors of disease progression. These four factors were included as continuous variables in a proportional hazards model to predict time to progression.

The model distinguished patients into 3 distinct groups consisting of a high-risk group with median time to progression of 1.8 years, an intermediate-risk group with median time to progression of 4.8 years, and a low-risk group with median time to progression of 9.3 years (P < .001). By combining available patient data from the Dana-Farber cohort and an additional cohort, there was sufficient statistical power to identify wild-type MYD88 as a significant independent predictor of disease progression in multivariate analysis (HR = 2.7).

The model was validated in external cohorts from Mayo Clinic, Rochester, and Greece. The investigators have made the model available as a Web page application at awmrisk.com.

The investigators concluded, “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 asymptomatic Waldenström’s macroglobulinemia who may need closer follow-up or benefit from early intervention.”

Irene M. Ghobrial, MD, of the Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Dana-Farber Cancer Institute, National Institutes of Health Grants, Leukemia and Lymphoma Society, International Waldenström Macroglobulinemia Foundation, and Michele and Stephen Kirsch Fund for Waldenström Macroglobulinemia. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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