The treatment of chronic lymphocytic leukemia (CLL) has changed significantly over the last 20 years, largely due to advances in therapeutics. Given high heterogeneity of the disease, some patients will require treatment at initial diagnosis, while others may never require therapy. Based on the 2018 International Workshop on CLL (iwCLL) guidelines, most patients with early-stage disease are not routinely offered treatment, but several ongoing clinical trials are investigating the role of early intervention in newly diagnosed, early-stage disease.1-2
In a review article published in Clinical Advances in Hematology & Oncology, Eli Muchtar, MD, of the division of hematology at the Mayo Clinic in Rochester, Minnesota, and colleagues summarized current literature surrounding the efficacy and safety of early intervention in CLL. In addition, they provided an overview of ongoing clinical trials of novel agents used in patients with early-stage disease.1
Historical Overview and Contemporary Prognostic Models
Early intervention is defined as the use of anti-CLL therapy in patients who otherwise would be under a “watch-and-wait” approach due to an absence of symptoms, which usually applies to newly diagnosed patients who do not meet criteria outlined in the 2018 iwCLL.
Over the past few decades, several studies have been conducted to determine if early intervention can improve outcomes. Several clinical trials have shown that administration of anti-CLL therapy in early-stage disease does not improve overall survival (OS). However, the arrival of optimized prognostic models, and recent approval of new oral therapies has provided an opportunity to reexamine the role of early treatment in newly diagnosed patients at high risk for disease progression.
After initial diagnosis, the risk for progression to symptomatic disease is highly variable. As a result, optimal patient selection is a key component of efforts to evaluate the benefits of early intervention. Prognostic models used for risk stratification have progressed from the early Rai and Binet staging system to current models that incorporate clinical, genomic, and biological factors. While these models were created mainly to predict OS, in terms of early intervention, the best risk model is one that accurately predicts time to first therapy.
At present, 4 such models exist, which include the MD Anderson Cancer Center (MDACC), German Chronic Lymphocytic Leukemia Study Group (GCLLSG), CLL International Prognostic Index (CLL-IPI), and the CLL prognostic model (CLL-PM).
Early-Intervention Studies in Asymptomatic CLL
Various studies of early intervention in patients with asymptomatic CLL are ongoing, and readers should refer to the full publication in Clinical Advances in Hematology & Oncology for a comprehensive list.