More than a decade without treatment: Time to first treatment in CLL in a chilean cohort

Abstract Background: Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease, with time to first treatment (TTFT) being a crucial surrogate endpoint for disease progression and prognosis. Most patients are asymptomatic at diagnosis and are managed with a “watch and wait” approach until treatment criteria are met. Few studies have evaluated TTFT in Latin American populations. Here, we describe the TTFT and its clinical predictors in a large multicenter cohort of Chilean patients with CLL and compare these findings to international reports. Methods: We retrospectively analyzed 273 consecutive adult patients diagnosed with CLL between 1995 and 2024 in public healthcare institutions across Chile. Baseline clinical variables included age at diagnosis, ECOG performance status, CIRS score, hemoglobin level, platelet and lymphocyte counts, Rai and Binet stage, CD38 expression, and serum markers (LDH, β2-microglobulin). TTFT was defined as time from diagnosis to initiation of first-line treatment and was estimated using Kaplan-Meier analysis. Cox proportional-hazard regression models were used to assess univariate and multivariate predictors of TTFT. Results: Of 273 patients, 111 (41%) initiated treatment during follow-up. The median TTFT was 9.95 years (95% CI: 4.47–not reached), significantly longer than the–5 years reported in most international series. Advanced age (≥70 years) was associated with longer TTFT (HR 0.48; p=0.001), possibly reflecting more conservative management in elderly patients or possibly less aggressive behavior of the disease. In contrast, hemoglobin <12 g/dl (HR 2.78; p<0.001), platelet count <150 ×10⁹/L (HR 2.15; p=0.001), absolute lymphocyte count ≥20 ×10⁹/L (HR 2.21; p<0.001), and positive CD38 expression (HR 2.59; p<0.001) were independently associated with shorter TTFT. Clinical stage remained a strong predictor of early treatment: intermediate/high Rai (HR 3.30 and 16.0) and Binet B/C (HR 6.83 and 12.3) were all associated with significantly reduced TFT (p<0.001). Estimated median TFT in low-risk patients was remarkably long: 26.7 years for low Rai or Binet A stages. Conversely, patients with high Rai or Binet C disease had a median TFT of less than one month. Conclusions: This is the first large-scale analysis of TFT in CLL in a Latin American population. The unusually prolonged TFT observed in this Chilean cohort suggests a highly indolent disease. Traditional clinical variables such as hemoglobin level, platelet count, lymphocyte count, and clinical stage as well as the Rai and the Binet Staging systems remain reliable and accessible predictors of treatment requirement. These findings support the continued relevance of the “watch and wait” strategy in CLL patients and underscore the need for prospective studies incorporating molecular and genetic prognostic markers in Latin American populations.