Background: While health-related quality of life (HRQOL) has been assessed in clinical trials, little is known about the real-world HRQOL of chronic lymphocytic leukemia (CLL) patients. This study’s objective was to describe HRQOL and treatment satisfaction of CLL ibrutinib (IBR)-treated patients in the real-world. Design: This is the second study of a two-part study. The first study (Norming) was an online survey of CLL patients (Treatment (Tx) naive n=64, 1 st line (1L) n=36, and 2+ lines (2L+) n=38) from a US panel. The study generated references for HRQOL and treatment satisfaction in real-world CLL patients not on IBR. This study (IBR CLL) includes CLL patients treated with IBR for ≥6 months in health system specialty pharmacies. Respondents completed demographic/clinical information and surveys via phone (Functional Assessment of Cancer Therapy-General [FACT-G], FACT-Leukemia, and Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue and Cancer Therapy Satisfaction Questionnaire [CTSQ]). Higher scores indicate better HRQOL and treatment satisfaction. Differences, at the group level, in effect sizes between the two studies were calculated using Hedges' g. Results: In an interim analysis of 23 IBR CLL patients, 10 patients were 1L, and 13 patients were 2L+. Mean age was 67.4±7.1 years, over 60% were male, and over 87% Caucasian. The average duration on IBR was 25.6±14.1 months. Comparatively, Norming Study patients were younger and nearly 50% female. Medium-large positive effects were seen in the IBR CLL group on almost all measures compared to the Norming Study groups, Figure 1. The FACT-G total score was 89.2±11.1 for IBR CLL Study patients compared to 75.8±22.6 Norming Study Tx naïve patients, 61.3±21.8 in 1L, and 61.7±20.7 in 2L+. Similar trends were seen with FACT-Leukemia (IBR CLL Study 139.9±19.1; Norming Study Tx naïve 121.8±35.9, 1L 101.4±36.3, and 2L+ 99.1±33.2) and FACIT-Fatigue (IBR CLL Study 39.9±10.1; Norming Study Tx naïve 35.5±14.4, 1L 29.5±12.9, and 2L+ 28.7±13.4), Table 1. IBR CLL Study patients scored higher on all CTSQ domain scores compared to the Norming Study patients treated with other CLL therapies. Conclusions: Similar to what has been reported in IBR CLL clinical trials, real-world IBR-treatment had large positive effects on HRQOL and treatment satisfaction compared to other therapies irrespective of line of therapy.