Risk and Survival Outcomes of Secondary Primary Malignancies in Chinese Lymphoma Patients in the Era of Modern Targeted Therapies: A Single-Center Retrospective Cohort Study.

Authors

Chen Qiu, Tingting Zhang, Xuejing Yang, Yafang Guo, Zihui Gong, Dong Song

Published in

Blood and lymphatic cancer : targets and therapy. Volume 16. Pages 616235. Epub Jul 14, 2026.

Abstract

With the advent of modern therapies, including rituximab and novel oral targeted agents such as BTK inhibitors, the survival of lymphoma patients has significantly improved. However, the risk of secondary primary malignancies (SPMs) remains a critical concern. This study aims to evaluate the incidence, risk factors, latency, and survival outcomes of SPMs in lymphoma patients treated in the era of targeted therapies.
A retrospective cohort study was conducted on 1,715 lymphoma patients diagnosed between October 2011 and October 2024 at Shanxi Bethune Hospital, China. Patients with incomplete records, pediatric cases, or immunodeficiency were excluded. Data on demographics, lymphoma characteristics, treatment modalities, and SPMs were collected. SPMs were classified as synchronous (diagnosed within 6 months of lymphoma) or metachronous (diagnosed after 6 months). Statistical analyses included Cox regression for risk factors and Kaplan-Meier for survival analysis.
Among 1,715 lymphoma patients, 65 (3.8%) developed SPMs, including 10 synchronous (0.6%, descriptive enumeration only), while 55 (3.2%) developed metachronous SPMs that constituted the primary analytic cohort. Aggressive B-cell non-Hodgkin lymphoma (43.6%) was the most common lymphoma subtype among patients who developed SPMs, followed by indolent B-cell non-Hodgkin lymphoma (38.2%). Digestive and respiratory system tumors were the predominant SPMs (34.5% and 23.6%, respectively). Multivariate analysis identified male sex, ECOG performance status ≥2, extranodal involvement, bone marrow infiltration, BTK inhibitor use, and radiotherapy as independent risk factors for SPMs. Competing-risk analysis showed a higher cumulative incidence of SPMs in patients exposed to BTK inhibitors than in those not exposed to BTK inhibitors (5-year CIF, 7.92% vs 2.57%; Gray's test [Formula: see text] =0.007). Kaplan-Meier analysis showed that patients with SPMs had significantly worse OS than those without SPMs (median OS, 10.3 years; 5-year OS, 69.6% vs 89.6%; log-rank [Formula: see text]<0.0001). No significant difference in OS was observed between patients with solid and hematologic SPMs (median OS, 12.8 vs 6.0 years; [Formula: see text]=0.76).
In the transitional era of conventional and targeted therapies, although data are limited.This exploratory analysis confirmed that gastrointestinal and respiratory SPMs predominated in this Asian cohort, and identified male sex, ECOG ≥2, extranodal involvement, bone marrow infiltration, radiotherapy, and BTK inhibitor use as independent risk factors. The association with BTK inhibitors (HR=2.56) warrants cautious interpretation and prospective validation. Early detection and tailored surveillance (prioritizing gastrointestinal screening) are essential for improving long-term outcomes.

PMID:
42472029
Bibliographic data and abstract were imported from PubMed on 19 Jul 2026.

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