Second primary malignancy risk in Hodgkin lymphoma survivors in the modern treatment era: A SEER MP-SIR analysis, 2000–2022.

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Background: Second primary malignancies (SPMs) remain a leading cause of late mortality among Hodgkin lymphoma (HL) survivors. Contemporary estimates reflecting reduced-field radiotherapy and the introduction of brentuximab vedotin and PD-1 inhibitors are limited. As modern HL therapy continues to shift toward individualized, risk-adapted approaches, updated population-level data are essential to assess whether these therapeutic advances have translated into reduced late toxicities. Methods: Patients with first primary HL diagnosed 2000–2022 were identified in SEER-17 registries (November 2024 submission). Follow-up began 12 months after diagnosis. Standardized incidence ratios (SIRs) and excess absolute risks (EARs per 10,000 person-years) were calculated using SEER*Stat MP-SIR, restricting second events to subsequent malignant tumors (event number ≥2). Analyses were stratified by age at HL diagnosis and calendar period. Results: Among 39,430 HL survivors contributing 366,836 person-years, 3,092 SPMs were observed (SIR 1.60, 95% CI 1.54–1.66; EAR 31.59). SIR declined from 1.78 (2000–2009) to 1.42 (2010–2022) (p-trend < 0.001). Highest relative risks occurred in patients diagnosed age 5–19 years, with SIRs 4.03–8.42. Lung cancer remained the most common solid SPM in older survivors (SIR ~4× risk), emphasizing the ongoing importance of smoking cessation and screening. These trends indicate a decline in SPM incidence in more recently treated patients. Follow-up for the most recent period was shorter, which may underestimate late SPMs, and individual treatment details were not available. Conclusions: Overall, SPM risk in HL survivors has declined compared with historical cohorts and is now only about 60% higher than the general population. These updated findings provide actionable guidance for risk-adapted survivorship care, highlighting the importance of targeted lung-cancer screening in older patients and offering practical information for counseling patients about their long-term risk.