What question did this study set out to answer?

This analysis aims to evaluate the risk of second primary malignancies in survivors of Hodgkin lymphoma treated with contemporary therapies.

June 26, 2026

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

Key Points

This analysis aims to evaluate the risk of second primary malignancies in survivors of Hodgkin lymphoma treated with contemporary therapies.
Identified patients with Hodgkin lymphoma diagnosed from 2000 to 2022 using SEER-17 registries.
Calculated standardized incidence ratios and excess absolute risks for second primary malignancies.
Stratified analyses by age at diagnosis and calendar period.
Among 39,430 survivors, 3,092 second primary malignancies were observed, with a SIR of 1.60 (95% CI 1.54–1.66).
SIR declined from 1.78 (2000–2009) to 1.42 (2010–2022), indicating a significant reduction (p-trend < 0.001).
The highest risks were in patients diagnosed at ages 5–19, especially for lung cancer, which remained a concern for older survivors.

Abstract

253 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.

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