In 2008, the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) established criteria for treatment indications. The Brazilian CLL Group (GBLLC) has been evaluating a more conservative approach in the indication and initiation of treatment carried out in multiple centers. This approach eschews predefined cut-off levels for cytopenias and refrains from considering progressive lymphocytosis, extranodal involvement, or disease-related symptoms as isolated criteria. However, the safety and potential divergent outcomes of this conservative strategy in comparison to the more stringent IWCLL criteria had not yet been tested.

To compare the outcomes of patients with CLL registered in the Brazilian CLL Registry (RBLLC) without indication of treatment according to the GBLLC criteria, who were treated or not based on the center's decision.

We performed a retrospective analysis of patients with CLL registered in the RBLLC who were followed between January 2009 and July 2023, meeting the minimum data availability criteria for analysis and following the IWCLL inclusion guidelines.

A total of 2,511 patients from 41 centers were included. Among them, 1,404 patients (56%) met the treatment indication criteria set by IWCLL, while only 788 patients (31%) met the more conservative criteria established by GBLLC. Predominant indications for treatment initiation in the IWCLL indication group included cytopenias in 771 patients (55%), symptomatic lymphadenopathy in 330 patients (24%), and disease-related constitutional symptoms in 112 patients (8%). In the GBLLC indication group, common indications for treatment initiation comprised cytopenias in 413 patients (52%), symptomatic lymphadenopathy in 316 patients (40%), and autoimmune complications in 22 patients (3%). After a median follow-up of 58 months, the 5-year overall survival (OS) was 82%. The group of patients whose treatment indication were cytopenias demonstrated inferior OS compared to those with other indications. Of the total of 1,404 patients who had an indication according to the IWCLL, 1,149 received therapy. Median time to first treatment (TTT1) was 3.4 months (range: 1 – 231). Upon evaluating the duration between the treatment indication and its initiation, patients who waited over 18 months exhibited a superior OS in contrast to those with a waiting period of fewer than 18 months (82% vs. 69%, respectively; p = 0.004). Among patients with treatment indication according to IWCLL but without indication according to the GBLLC criteria, OS was significantly worse in treated patients (83%) as compared with untreated patients (97%, P < 0.0001). After multivariate analysis, receiving treatment was an independent risk factor for OS in patients with indication according to the IWCLL and but not to the GBLLC criteria.

These real-world data suggest that a conservative approach to first-line treatment for CLL is not only safe but also linked to enhanced survival, potentially by reducing treatment-related toxicities and complications, such as infections, toxicities and clonal selection. Additionally, this strategy holds the potential to save resources improving access to medications for a larger pool of patients with a clear need for treatment, particularly in resource-limited countries.