OUTCOMES OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) ACCORDING TO THE REASONS FOR INITIATION OF FIRST-LINE TREATMENT: A RETROSPECTIVE ANALYSIS OF THE BRAZILIAN REGISTRY OF CLL

Abstract

Objective: To describe the outcomes of different reasons for initiating first-line treatment in a series of patients with CLL. Methods: Retrospective observational study with all patients with CLL in the Brazilian Registry of CLL(RBCLL), that was started in 2004. Results: Between January 2004 and March 2021, a total of 1654 patients were followed at 30 centers. After a median follow-up of 86 months (range:3-315), there were 864 patients (52%) who were not treated, and 790 (48%) who were treated. Among the untreated patients, 636 (74%) did not have treatment indication while 228 (26%) had treatment indication but were not treated. These patients were not treated despite having an indication because of the following reasons:more conservative treatment indications in 59% of cases, death during follow up from unrelated causes in 15%, early death associated with poor clinical condition in 5% of cases, and for unknown reasons in 21%. Among 790 patients who were treated, the most common reasons for treatment initiation were cytopenias in 56%, and symptomatic lymphadenopathy in 26%. Other indications: disease-related constitutional symptoms in 22%, progressive lymphocytosis in 15%, symptomatic splenomegaly in 11%, and extranodal disease and steroid-refractory autoimmune complications in 1%, each. Besides,50 patients (7%) were treated although did not have a treatment indication. Treatment-free survival (TFS) was 37% at 8 years. It was only 10% for those with treatment indications due to cytopenias or lymphadenopathy, 25% for those with other treatment indications and 78% for those without indication (p < 0.0001). Median time between diagnosis and first-line treatment initiation was significantly shorter in patients with treatment indication due to cytopenias (7 months), and in those treated due to lymphadenopathy (13 months), than in those due to other reasons(37 months), and those without treatment indication (median not reached, p < 0.0001). Cytopenias as a reason for treatment initiation was associated with inferior TFS even among Binet A and B patients (median time 30 months vs. not reached). Analyzing the 375 patients who were treated due to cytopenias, anemia (hemoglobin<10 g/dL) was significantly associated with worse survival (27% vs. 55%, p < 0.0001), while thrombocytopenia (platelets<100x109/L) had no impact on survival. Overall survival (OS) was 61% at 8 years among treated patients. OS was significantly worse in patients who were treated due to cytopenias (48%) than in those treated for other reasons (75%, p < 0.0001). Cytopenia as an indication of treatment was associated with inferior OS even among Binet A and B patients (79% vs. 63%, p = 0.002). Indeed, after correcting for age,Binet staging and renal function, cytopenias remained significantly associated with worse OS(hazard ratio–HR:2.98,95% confidence interval 1.26-7.06). Progressive lymphocytosis as a treatment indication was associated with a significantly better OS (73%vs.58%, p = 0.002), although the protective effect did not remain after a multivariate analysis. Median time-to-next treatment (TTNT) after first-line treatment was 40 months. Median TTNT was also significantly shorter for patients treated due to cytopenias (30 months) than for those treated due to lymphadenopathy (71 months), and due to other reasons (56 months, p < 0.0001). Conclusion: Cytopenias and lymphadenopathy were the most common reasons for treatment initiation. Cytopenias as a reason for treatment initiation was associated with inferior OS and TFS, as well as TTNT and should therefore be regarded as an independent risk factor for worse outcome in patients with CLL. These real-world data may help clinicians to choose wisely when and for whom to initiate therapy in CLL.