Second Primary Malignancies in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Comprehensive Review

Patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) have benefited significantly over the last decade from the approval of several novel, targeted therapeutic agents, resulting in prolonged overall survival. However, an excess mortality for CLL/SLL patients remains largely due to nondisease progression events, including second primary malignancies (SPMs). Estimates on the contribution of SPMs to overall excess morbidity and mortality in CLL patients are varied, but recent literature suggests SPMs are responsible for up to 20% of deaths in CLL patients, and studies consistently show CLL patients with an SPM have inferior overall survival than those without an SPM. SPMs are a particularly relevant practice consideration as CLL survival increases in the era of targeted therapies; however, the literature is lacking in comprehensive reviews of SPM in CLL/SLL during the contemporary treatment era. This article summarizes the incidence and prevalence of SPM and the current understanding of various disease- and treatment-related factors involved in SPM development in the era of available novel therapies, and current screening guidelines will be highlighted where relevant. In addition to updating the literature in a cohesive review, this article aims to heighten awareness of SPMs in CLL/SLL with an emphasis on informing provider practice of current screening guidelines and identifying the gaps in understanding for future studies inclusive of SPM in CLL.