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Novel PANGEA Models May Improve Clinical Prediction of Disease Progression to Myeloma

By: Vanessa A. Carter, BS
Posted: Tuesday, September 27, 2022

Irene Ghobrial, MD, of the Dana-Farber Cancer Institute, Boston, and colleagues created the PANGEA models—which use time-varying biomarkers to improve clinical prediction of patients at risk of disease progression to multiple myeloma—to redefine disease states of monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. During the 2022 International Myeloma Society (IMS) Annual Meeting and Exposition (Abstract OAB-036), the investigators presented details about these models.

“Together, the PANGEA Model (bone marrow), PANGEA Model (no bone marrow), and PANGEA Model (fluorescence in situ hybridization [FISH]) reform current monoclonal gammopathy of undetermined significance and smoldering multiple myeloma risk criteria by either allowing incorporation of cytogenetic information or estimating risk without bone marrow data,” concluded the study authors. “We also define a spectrum of risk of progression that replaces monoclonal gammopathy of undetermined significance/smoldering multiple myeloma dichotomization with personalized risk estimates for individual patients.”

The investigators retrospectively assembled a cohort of 6,441 patients with either monoclonal gammopathy of undetermined significance (n = 4,931) or smoldering multiple myeloma (n = 1,510) at baseline. Biological and clinical variables were measured at baseline and serial timepoints to model the risk of disease progression to multiple myeloma.

The PANGEA Model was trained with or without bone marrow–specific variables, as well as time-varying biomarkers such as age, free light chain, bone marrow plasma cell percentage, creatinine and monoclonal protein, and dynamic trajectories including creatinine and hemoglobin. Of note, both the bone marrow and no–bone marrow PANGEA Models appeared to outperform previous models, demonstrating 43% and 30% higher C-statistic values, respectively, when compared with a previous model in a validation cohort. When cytogenetic variables were introduced in the FISH model, an increased risk of disease progression was identified in individuals who had chromosome 17/17p or 13/13q deletions, chromosome 1q gain, and MYC aberrations.

Disclosure: Disclosure information was not provided.

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