Currently, there are no molecular indications for the initiation of treatment for CLL. Rather, treatment is determined based on the patient’s symptoms and tumor volume. Models have been developed as prognostic tools to identify patients with early stage, asymptomatic CLL who are at risk for progression and therefore are possible candidates for early therapy. For example, Condoluci and colleagues developed a model based on the following 5 identified variables that were independently associated with time to first treatment: (1) lymphocyte count higher than 15 G/L; (2) palpable lymph nodes; (3) palpable spleen; (4) unmutated immunoglobulin heavy chain variable region (IGHV) gene; and (5) trisomy 12. Testing for lymphocyte count and examining the lymph nodes and spleen are steps that we already take clinically to determine the need for treatment. While the model by Condoluci et al identifies those at highest risk, in my opinion, it would be more useful to incorporate biomarkers above and beyond the clinical variables that are already used.

The CLL International Prognostic Index is a model that incorporates cytogenetic and clinical variables (ie, TP53 mutational status; IGHV  mutational status; serum b₂-microglobulin concentration, clinical stage, age) to predict 5-year survival. With respect to the active monitoring of early disease, there are no clear guidelines for when to perform a computed tomography (CT) scan for lymph node involvement. In general, if the patient has no abdominal symptoms and is doing well otherwise (ie, is asymptomatic), I would not routinely order an abdominal CT scan. Individual patient preferences and attitudes regarding their own disease can also be important when managing early stage CLL. Some patients with asymptomatic disease are content with a watch and wait approach, while others find an initial plan that does not include active treatment conceptually unappealing, even when the evidence-based rationale for this practice is explained. I often will tailor my approach accordingly: For those patients who agree with the idea of no initial treatment, there is no urgency to obtain prognostic factors immediately. For those who are more skeptical of a watch and wait approach or who want to be more involved and proactive in their treatment, I often obtain prognostic information earlier on. Patients in the latter category also tend to be the most interested in enrolling in clinical trials on early CLL. It is particularly difficult to develop surrogate end points that would predict long-term outcomes. That being said, such trials are being planned and conducted in high-risk or very high–risk CLL based on International Prognostic Index scoring. If a trial were to show a benefit of early treatment for a subset of patients with high-risk, early stage, asymptomatic CLL, it would be practice changing.