Identifying patients with chronic lymphocytic leukemia without need of treatment: End of endless watch and wait?

Abstract

Early-stage chronic lymphocytic leukemia (CLL) challenges specialized management and follow-up. We developed and validated a prognostic index to identify newly diagnosed patients without need of treatment (CLL-WONT) by a training/validation approach using data on 4708 patients. Composite scores derived from weighted hazards by multivariable analysis defined CLL-WONT risk groups. Age (>65years: 1 point), Binet stage (B: 2 points), lactate dehydrogenase (LDH) (>205U/L: 1 point), absolute lymphocyte count (15-30×109 /L: 1 point; >30×109 /L; 2 points), β2-microglobulin (>4mg/L: 1 point), IGHV mutation status (unmutated: 1 point), and 11q or 17p deletion (1 point) were independently associated with shorter time to first treatment (TTFT). Low-risk patients demonstrated 5-year TTFT of 2% by internal validation, but 7-19% by external validation. Including all patients with complete scores, the 5-year TTFT was 10% for the 756 (39%) CLL-WONT low-risk patients, and the 704 (37%) patients who were both CLL-WONT and CLL-IPI low risk demonstrated even lower 5-year TTFT (8%). We have adopted the CLL-WONT at an institution covering 1800000 individuals to allow patients with both low-risk CLL-WONT and CLL-IPI to be managed by primary healthcare providers, thereby prioritizing specialized hematology services for patients in dire need.