Racial and ethnic disparities in the risk of second primary malignancies among diffuse large B-cell lymphoma survivors in the United States Free

Background: Previous studies have shown an increased risk of second primary malignancies (SPMs) among diffuse large B-cell lymphoma (DLBCL) survivors; however, this has not been comprehensively examined by race/ethnicity. We utilized a large population-based database to examine disparities in SPM risk by race/ethnicity.

Methods: From 17 United States population-based Surveillance, Epidemiology and End Results (SEER) program cancer registry areas, we identified 68,358 ≥12-month first-primary DLBCL survivors diagnosed between 2000-2022. Standardized incidence ratios (SIRs) and accompanying 95% confidence intervals (CIs) quantified SPM risk by race/ethnicity (non-Hispanic White, Black, Asian/Pacific Islander [API] and Hispanic), compared with the general population.

Results: Overall, we observed 6,261 SPMs after DLBCL representing a 1.2-fold significantly increased risk (95% Confidence Interval [CI]=1.16-1.22) compared to the general population and an excess of 23 cases per 10,000 person-years. SIRs for all second cancers combined varied significantly by race/ethnicity with APIs and Hispanics presenting higher overall SPM risk (SIR_API=1.36; CI=1.23-1.50, and SIR_Hispanic=1.35; CI=1.25-1.45) compared to the White and Black patients (SIR_white=1.15; CI=1.12-1.19 and SIR_Black=1.19; CI=1.08-1.31) (P-heterogeneity<0.001). Heterogeneity by race/ethnicity in SIRs was even more pronounced in younger, particularly the adolescent and young adult (AYA) patients aged between 20 to 39 years at DLBCL diagnosis. Significantly elevated SPM risk was observed among the Hispanic and API AYA DLBCL survivors (SIRs of 3.03 and 2.68, respectively), followed by the corresponding Black and White patients (SIRs of 2.48 and 1.89, respectively) (P-heterogeneity<0.01). Similar patterns in racial/ethnic and age-related disparity were observed by patient's sex and latency, with higher SPM risk among the young female minority patients who were within first 5 years since DLBCL diagnosis. Although SIRs for SPM were significantly higher after advanced stage DLBCL (compared to a localized/regional disease), or among patients who received chemotherapy or radiation (compared to those who didn't), heterogeneity by race/ethnicity in SPM risk was significant regardless of the stage or receipt of these treatments.

Results from site specific analyses reported significantly higher overall SIRs for second hematological malignancies compared to solid cancers (SIR_hemat=3.40; CI=3.15-3.68 and SIR_solid=1.07; CI=1.04-1.10); and patterns by race/ethnicity also varied significantly by these second cancer sites. Among the second primary solid cancers, strikingly elevated risks (SIRs>5) were observed for anal cancer among the Black and Hispanic DLBCL patients (SIRs of 9.29 and 8.55, respectively), compared to the White or the API. Whereas, among the second primary hematological malignancies, risks were particularly elevated for Hodgkin Lymphoma (HL) and Acute Non-Lymphocytic Lymphome (ANLL). HL risk was strikingly high among the minority populations, such as the API, Black and Hispanic DLBCL survivors, compared to the White (SIRs of 23.39, 13.88, 10.06 and 7.99, respectively). Similarly, ANLL risk was also significantly higher among the minority DLBCL patients, with SIRs of 9.33, 9.07 and 8.41 for patients belonging to the Black, API and Hispanic race/ethnicity compared to the SIR or 6.19 for White patients (P-heterogeneity=0.003).

Conclusion: Using a large-scale population-based data, we observed substantial disparities in SPM risk by race/ethnicity, with patients belonging to minority groups experiencing higher risks. Further research to understand drivers of these observed racial/ethnic heterogeneity (e.g. baseline incidence of clonal hematopoiesis) and evaluation of tailored cancer surveillance strategies to reduce morbidity from SPM in DLBCL survivors is warranted.