Study on Treatment Outcome Patterns for Patients With CLL After Discontinuation of BTK Inhibitors

EFS will be defined as the proportion of patients who remain alive, do not meet International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria for initiation of next chronic lymphocytic leukemia (CLL) therapy, and have not started a new CLL - directed treatment.

Progression Free Survival (PFS) will be defined as the proportion of patients who remain alive, free of relapse from complete response or partial response, free of progression of chronic lymphocytic leukemia (CLL), and have not started a new CLL treatment at 2 years after discontinuation of Bruton tyrosine kinase inhibitors (BTKi).

Overall Survival (OS) will be defined as the proportion of patients who remain alive after discontinuation of Bruton tyrosine kinase inhibitors (BTKi).

Time to initial detection of measurable residual disease (MRD) or clinical evidence of progression will respectively be defined as the time from discontinuation of BTKi to initial detection of MRD (via flow cytometry) or progression of CLL that meets IWCLL criteria and/or treating physician requirement for initiation of next CLL therapy.

Overall and complete response rates will be defined as the percentage of patients who respectively achieve overall and complete response to next CLL therapy, based on IWCLL criteria.

Rate of resolution of BTKi-related adverse events will be defined as the percentage of patients whose adverse events attributed to BTKi treatment have improved, subsided, or completely disappeared after discontinuation of BTKi, to the extent that the patient's condition returns to baseline or to a clinically acceptable grade (typically Grade ≤ 1 per CTCAE) as graded by NCI CTCAE v5.0 and Quality of Life assessments.

Incidence of new infections will be defined as the percentage of patients who respectively have new infections after discontinuation of BTKi

Incidence of second cancers will be defined as the percentage of patients who respectively have second cancers after discontinuation of BTKi.

Association between biomarkers and disease outcomes as defined by EFS, PFS, OS, PFS, duration of response, duration of MRD undetectable disease state, and Richter's transformation (transforms into a fast-growing lymphoma).

Change in FACT -Leukemia Total Score from prior to discontinuation of BTKi to 6 months after discontinuation of BTKi.

The FACT-Leukemia is a patient-reported outcome questionnaire designed to assess quality of life in patients with leukemia. It includes 27 general items covering physical, social/family, emotional, and functional well-being, along with 17 leukemia-specific items addressing symptoms, treatment concerns, and side effects, for a total of 44 items. Each item is rated on a 5-point Likert scale from 0 ("Not at all") to 4 ("Very much"), with some items reverse-scored for consistency. Scores are summed to create subscale scores and a total score, with higher scores indicating better quality of life. The instrument is commonly used in clinical trials and routine care to monitor patient well-being, evaluate treatment impact, and assess the effects of therapy from the patient's perspective.

Change in FACT-Leukemia physical, social, emotional, and functional well-being component scores from prior to discontinuation of BTKi to 6 months after discontinuation of BTKi FACT-Leu evaluates patient-reported quality of life across four domains: physical, social/family, emotional, and functional well-being, capturing how a patient's condition evolves over time during or after treatment. Each domain consists of multiple items scored on a 5-point Likert scale ranging from 0 ("not at all") to 4 ("very much"), with domain scores calculated by summing item responses within each domain. A total score may be derived by summing the four core domains (FACT-G) and, when applicable, including leukemia-specific items for the FACT-Leu total score. Higher scores indicate better quality of life.