Longitudinal Analysis of Patient Reported Quality of Life in Newly Diagnosed Chronic Lymphocytic Leukemia Stratified By Initial Management Strategy: A Multi-Institutional Prospective Cohort Study

Introduction: The treatment of chronic lymphocytic leukemia (CLL) has evolved over the past two decades, from finite duration chemoimmunotherapy (CIT) to an era of targeted agents such as Bruton Tyrosine Kinase (BTK) inhibitors, BCL2 inhibitors, and anti-CD20 monoclonal antibodies. Little is known about how initial management strategy (watch and wait [W&W] vs. treatment) at diagnosis impacts patient reported outcomes (PROs) in CLL survivors over time, particularly in light of therapeutic advances over the last decade. Methods: Newly diagnosed CLL patients were prospectively enrolled within 9 months of diagnosis in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER1) study between 9/1/02 and 6/30/15, and within 6 months of diagnosis in the MER Phase 2 (MER2) study between 7/1/15 and 5/1/20. PROs were measured using the Functional Assessment of Cancer Therapy-General scale (FACT-G), which generates Physical (PWB, range 0-28), Social/Family (SFWB, 0-28), Emotional (EWB, 0-24), and Functional Well-Being (FWB, 0-28) scores and a Total Score (0-108), with higher scores indicating better WB. In both cohorts, FACT-G was measured at enrollment and at years 1, 2, and 3 after diagnosis, while the timing of later assessments varied slightly by study (MER1: 6 yrs and 9 yrs; MER2: 5 years). We employed a generalized linear mixed model to evaluate change from baseline between groups with groups defined by each participant's initial management strategy (W&W vs. upfront systemic treatment). Initial management strategy was determined by the treating physician. The study was approved by the Mayo Clinic IRB. Results: A total of 722 patients were identified in MER1 and 256 patients in MER2. The median age at diagnosis was 63 years in MER1 and 66 years in MER2 (P0.05). More patients initiated upfront systemic therapy in MER1 (n=380, 53%) than in MER2 (n=110, 43%). Other baseline clinical characteristics were similar between the cohorts ( Table 1). There was no statistical difference in the mean FACT-G total score at baseline between MER1 (85.0, SD 12.5) and MER2 (85.2, SD 12.7). In the MER1 cohort, statistically significant lower baseline QOL scores were observed in patients initiating upfront treatment compared to W&W on the FACT-G total score (P=0.002) as well as the PWB (P=0.01), EWB (P=0.03), and FWB (P=0.006) subscales. We also observed that over time, EWB and FWB scores were consistently