Abstract 1569: Racial differences in incidence and impact of TP53 deletion on outcome in African American and Caucasian veterans with multiple myeloma
Authors: Cirstea Diana , Fillmore Nathanael , Yameen Hassan , Yellapragada Sarvari , Ifeorah Chizoba , Do Nhan , Brophy Mary , Munshi Nikhil 
Published: August 2019

BACKGROUND: In multiple myeloma (MM), the presence of TP53 deletion is associated with poor prognosis. It is found in roughly 10% of newly diagnosed patients. Lower incidence of TP53 deletion is reported in African American (AA) compared to Caucasian (CA), suggesting a possible contribution of disease biology to clinical disparity in AA. Our recent report of a significantly superior age-adjusted risk of death in AA compared to CA patients in the Veteran population also suggests possible racial differences in disease biology. Here we investigated the incidence of TP53 deletion among younger (&lt;65) versus older AA and CA patients with MM at the VA.

METHODS: We identified 15717 patients with MM from 1999 to 2017 using the VA’s nationwide Corporate Data Warehouse. We extracted data on patients’ age, race, and ISS stage, as well as data on their therapy at induction and stem-cell transplant (SCT). Additionally, we extracted data on TP53 deletion testing and results using a natural language processing algorithm and focused our analysis on patients with these data.

RESULTS: We identified 5,744 MM patients evaluated for TP53 deletion by conventional cytogenetics and/or FISH, including 32.5% AA (1,864) and 67.5% CA (3,880) patients. Greater proportion of AA patients (53%) were younger (&lt;65 years), compared to CA (39%; p&lt;0.001). Overall, among those tested, TP53 deletion was reported in 9.6% of patients, but the incidence was significantly lower in AA (7.2%) compared to CA (10.7%; p&lt;0.001). Among patients &lt;65 years of age, difference in incidence of TP53 deletion between AA and CA was 3.2% (8.1% vs 11.3%; p=0.01), while in those ≥65 years age, it was 4.1% (6.4% vs 10.5%; p=0.0005), suggesting increased difference in the incidence of TP53 deletion with age. The rates of TP53 deletion across different ISS stages were not significantly different, nor did ISS stage differ across race. The majority of patients with TP53 deletion (95.2%) received either proteasome inhibitor or immunomodulator at induction, but only 24.7% were treated with the combination, and only 21.4% proceeded to SCT. Median survival among younger patients with TP53 deletion appeared substantially lower in AA than in CA (5.1 vs 7.0 years; p=0.74), though without reaching significance, perhaps due to sample size. In contrast, younger AA without TP53 deletion had a significantly longer median survival than CA (8.0 vs 6.2 years; p&lt;0.01). Among older patients, AA had longer median survival regardless of TP53 deletion status.

CONCLUSIONS: This large cohort study identified significantly lower incidence of TP53 deletion in AA compared to CA. Yet, when present in younger AA patients, TP53 deletion correlated with worse survival. These results identify racial disparity in both occurrence and impact of TP53 deletion and now suggests the need for a more comprehensive genetic assessment to develop risk stratification in AA myeloma patients.

Citation Format: Diana Cirstea, Nathanael Fillmore, Hassan Yameen, Sarvari Yellapragada, Chizoba Ifeorah, Nhan Do, Mary Brophy, Nikhil Munshi. Racial differences in incidence and impact of TP53 deletion on outcome in African American and Caucasian veterans with multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1569.