Risk Factors beyond Chemotherapy Exposure for Secondary Myeloid Neoplasms after Hematologic Cancers: A SEER-Based...

As survival rates for lymphoid malignancies continue to improve, understanding the late effects after treatment, such as secondary myeloid neoplasms (sMN), is increasingly critical for survivorship. This large-scale population-based (SEER-Medicare) study investigated the risk factors and cumulative incidence of sMNs in patients with diagnosis of diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and multiple myeloma between 2000 and 2011, with follow-up through 2015. Patients with FL had a continuous increase in the cumulative incidence of sMNs with longer follow-up, whereas incidence of patients with multiple myeloma plateaued after 60 months. Notably, patients with DLBCL diagnosed in more recent years (2004-2007 and 2008-2011) had a higher cumulative sMN incidence compared with those diagnosed earlier (2000-2003). In the Medicare population, older age at diagnosis was associated with significant increase in sMN risk in patients with DLBCL and FL. Chemotherapy exposure or G-CSF exposure significantly increased sMN risk across all three malignancies. Chronic autoimmune conditions increased sMN risk in patients with DLBCL. These findings provide crucial insights into sMN risk factors. Chemotherapy exposure is a recognized risk factor, and comorbidities such as a history of autoimmunity and G-CSF exposures have been identified as additional mediators of sMN risk in our study.

Our study reveals population-level risk factors for sMNs, including novel links to autoimmune disease and G-CSF, in addition to known causes like chemotherapy/radiation. These findings underscore the complex pathogenesis of sMNs and the need for molecular data in prospective studies to guide prevention, detection, and survivorship care.