Overall Survival In Early Stage Chronic Lymphocytic Leukemia Patients With Treatment Indication Due To Disease Progression: Follow-Up Data Of The CLL1 Trial Of The German CLL Study Group (GCLLSG)

Introduction Chronic lymphocytic leukemia (CLL) is typically diagnosed at an early stage and a watch & wait (W&W) strategy is applied. Only when the disease progresses to a more active, symptomatic form, treatment is indicated. The prospective CLL1 trial was designed to evaluate the benefit of early risk-adapted therapy with fludarabine (F) monotherapy, and to document the natural course of the disease from diagnosis. Here we present follow-up data to assess overall survival from the time point of treatment indication. Methods At enrolment, risk stratification was performed based on bone marrow (BM) infiltration pattern, lymphocyte doubling time (LDT), serum beta2-microglobulin (s2-MG), and serum thymidine kinase (TK). Pts were “high-risk” (HR) if they had diffuse BM infiltration pattern and/or LDT 7.0 U/L and/or s2-MG >3.5 mg/L at enrolment. HR pts were randomized in a 1:1 ratio to early F (HR-F), or to W&W until classical treatment indication (HR-W&W), which was also applied to all low-risk (LR) pts. Results Between 1997 and 2004, 710 pts with Binet A stage CLL were enrolled and underwent risk stratification (RS) per protocol. Median time from diagnosis to enrolment was 3.2 mo (range 0-33.7) and median follow-up time was 8.5 years (yrs) (range 0-13.9). 521 pts (73%) were stratified to LR and 189 pts (27%) to HR, of whom 93 pts (49%) were randomized to HR-F and 96 pts (51%) to HR-WW high-risk cytogenetic features (17p- and 11q-) had 3% and 8% of pts, respectively. Early intervention with F among HR pts significantly prolonged progression-free survival (PFS) (30 vs. 13 mo; p 3.5 mg/L, and age >60 yrs as independent prognostic factors for OS for patients with progressive, active disease and treatment indication. Conclusions Monotherapy with fludarabine is not superior to the W&W approach for the management of early stage CLL pts, since early F did not improve OS or outcome following subsequent therapies. Disclosures: No relevant conflicts of interest to declare.