Background

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma. With more patients surviving initial therapy, the risk of second primary malignancies (SPMs) is an important survivorship concern. We evaluated overall, site-specific, and racial patterns of SPM risk among DLBCL survivors using a population-based dataset.

Methods

Using SEER 18 registries (2000–2022), we performed a Multiple Primary–Standardized Incidence Ratio (MP-SIR) analysis. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated overall, by latency (6–11, 12–59, 60–119, ≥120 months), cancer site, and race. All reported SIRs with CIs were considered statistically significant at p < 0.05.

Results

Among 83,014 survivors contributing over 533,000 person-years, 9,989 SPMs were observed versus 7,588 expected (SIR 1.32; 95% CI: 1.29–1.34). Risk peaked at 6–11 months (SIR 1.44; 95% CI: 1.34–1.54) and persisted across 12–59 months (SIR 1.34), 60–119 months (SIR 1.28), and ≥120 months (SIR 1.30). Hematologic malignancies had the greatest excess: Hodgkin lymphoma (SIR 8.57; 95% CI: 7.25–10.07), acute myeloid leukemia (SIR 6.29; 95% CI: 5.71–6.90), acute monocytic leukemia (SIR 7.07; 95% CI: 4.43–10.7), and chronic myeloid leukemia (SIR 2.21; 95% CI: 1.71–2.81). Among solid tumors, high-risk sites included anus (SIR 2.81; 95% CI: 2.23–3.50), salivary gland (SIR 2.79; 95% CI: 2.14–3.58), thyroid (SIR 2.16; 95% CI: 1.88–2.46), tongue (SIR 1.62; 95% CI: 1.31–1.98), stomach (SIR 1.51; 95% CI: 1.30–1.74), liver (SIR 1.67; 95% CI: 1.46–1.91), esophagus (SIR 1.28; 95% CI: 1.05–1.55), kidney (SIR 1.20; 95% CI: 1.08–1.35), and melanoma of the skin (SIR 1.23; 95% CI: 1.12–1.35). Racial disparities were marked: White (SIR 1.29; 95% CI: 1.27–1.32), Black (SIR 1.37; 95% CI: 1.26–1.48), American Indian/Alaska Native (SIR 1.96; 95% CI: 1.45–2.59), and Asian/Pacific Islander (SIR 1.57; 95% CI: 1.45–1.69). All reported site-specific risks were statistically significant (p < 0.05).

Conclusion

DLBCL survivors experience a sustained, clinically significant excess risk of SPMs extending beyond a decade, driven by secondary hematologic malignancies and high-risk solid tumors of the gastrointestinal tract, endocrine system, and head and neck. Pronounced racial disparities highlight the urgent need for risk-adapted surveillance and equitable survivorship care strategies.

Impact Statement:

DLBCL survivors face a persistent and clinically significant excess risk of second primary malignancies beyond 10 years, including high-risk solid tumors and hematologic malignancies. Pronounced racial disparities underscore the urgent need for equitable, risk-adapted survivorship strategies.

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2025
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