April 29, 2019
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New model identifies risk for Waldenström macroglobulinemia progression

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Researchers at Dana-Farber Cancer Institute have developed a classification system to determine whether a patient with asymptomatic Waldenström macroglobulinemia has a low, intermediate or high risk of developing symptomatic disease.

The progression risk-based classification system could inform patient monitoring and care, according to study results published in Journal of Clinical Oncology.

Irene Ghobrial, MD
Irene Ghobrial

“This study is part of the efforts conducted by the Center for Prevention of Progression of Blood Cancers (CPOP) at Dana-Farber that aim to understand how blood cancers progress over time from early precursor stages,” Irene Ghobrial, MD, director of CPOP and the Michele & Steven Kirsch Laboratory for Waldenström’s Research, said in a press release. “We also try to identify biomarkers that predict cancer progression and provide these patients with early therapeutic interventions.”

Waldenström macroglobulinemia is a rare form of non-Hodgkin lymphoplasmacytic lymphoma of the bone marrow marked by production of monoclonal immunoglobulin M (IgM) protein —which gathers in the blood, weakens circulation and can cause complications.

Researchers studied 439 patients with asymptomatic Waldenström macroglobulinemia (median age at diagnosis, 61 years; range, 26-91; 62.2% men) who had been diagnosed and observed at Dana-Farber from 1992 to 2014 to determine risk factors for progression to symptomatic disease.

Progression to symptomatic Waldenström macroglobulinemia that required chemotherapy served as the primary endpoint.

Median follow-up was 7.8 years.

Seventy-two percent of patients (n = 317) progressed to symptomatic disease during the 23-year study period.

Median time to progression from diagnosis of asymptomatic disease to symptomatic disease was 3.9 years (95% CI, 3.2-4.6), and the probability of progression within 2 years of diagnosis was 30.8% (95% CI, 26.7-35.3).

Independent predictors of disease progression included IgM of 4,500 mg/dL or greater, bone marrow lymphoplasmacytic infiltration of 70% or greater, 2-microglobulin of 4 mg/dL or greater, and albumin levels less than 3.5 g/dL.

Using these four values as continuous measures, researchers trained and cross-validated a proportional hazards model to evaluate progression risk. The risk model stratifies patients into three groups: high risk (median time to progression [TTP], 1.8 years), intermediate risk (median TTP, 4.8 years) and low risk (median TTP, 9.3 years).

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Results showed the following 2-year progression rates:

63.6% (95% CI, 49.7-77.4) for patients with IgM of 4,500 mg/dL or greater vs. 25.7% (95% CI, 21.5-30.6) among patients with lower levels;

61% (95% CI, 52-70.1) for patients with bone marrow lymphoplasmacytic infiltration of 70% or greater vs. 20.6% (95% CI, 16.6-25.4) among patients with lower levels;

65.3% (95% CI, 42.2-87.1) for patients with 2-microglobulin of 4 mg/dL or greater vs. 28.1% (95% CI, 22.6-34.6) among patients with lower levels; and

60.7% (95% CI, 43.5-78.3) for patients with albumin levels less than 3.5 g/dL vs. 27.1% (95% CI, 21.8-33.3) among patients with higher levels.

“‘We validated this model on two external cohorts, one in the [United States] from Mayo Clinic and the other from the University of Athens in Greece,” Romanos Sklavenitis Pistofidis, MD, postdoctoral fellow in the department of medical oncology at Dana-Farber Cancer Institute, said in a press release. “Our model was able to identify high, intermediate, and low-risk patients with high accuracy and precision in different patient populations.”

The researchers made the risk model available in the form of a calculator online at www.awmrisk.com. – by John DeRosier

Disclosures: Ghobrial reports consultant roles, honoraria and/or travel expenses from Amgen, Bristol-Myers Squibb, Celgene Novartis, Noxxon Pharma, Onyx and Takeda. Pistofidis reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.