Real-World Outcomes with Ibrutinib in Patients with Chronic Lymphocytic Leukemia: Impact of Patient Typology on Adherence and Retention Rates within the German REALITY Study

Introduction

An individual's experience of health is unique, and this experience has a significant impact on treatment adherence. One method used to quantify the health experiences of a patient (pt) divides pts into typology categories determined by their acceptance of, and their perceived control over, a disease. Acceptance is the feeling of a pt that their health status is acceptable. Perceived control is the belief of the pt that their health status can be controlled by themselves or others. Emotive support can modulate acceptance of disease (Bloem et al. BMC Health Serv Res 2020) and a pt's typology can influence treatment adherence and disease outcomes. REALITY was a prospective, non-interventional, real-world study of pts with chronic lymphocytic leukemia (CLL), which evaluated ibrutinib (a once-daily Bruton's tyrosine kinase inhibitor) effectiveness as a 1st-, 2nd- or ≥3rd-line treatment (cohorts C1, C2 and C3, respectively). This analysis evaluated pt typology in relation to treatment adherence and retention rates over 1 year (y). Treatment adherence is important for CLL treatment with ibrutinib, which is an oral treatment taken daily for optimal efficacy.

Methods

Pts with CLL received once-daily single-agent ibrutinib treatment (2.6% of pts with bendamustine + rituximab) across 57 sites in Germany (Jan 2017-Jul 2021) and were observed for up to 4 y. Pts completed a typology questionnaire at baseline (BL) and every 3 months (m) thereafter, up to 2 y. Questions were answered using a scale of 1-7, with average scores of ≥5.3 and ≥5.6 as the threshold for high acceptance and high control, respectively. Pts were then divided into four typology categories: high acceptance/high control (HA/HC), high acceptance/low control (HA/LC), low acceptance/high control (LA/HC) or low acceptance/low control (LA/LC). Adherence to ibrutinib treatment was determined using the eight-item Morisky Medication Adherence Scale questionnaire (total scores ranged from 0-8, and scores of <6, 6 to <8, and 8 reflected low, medium and high adherence, respectively) and pt retention rates defined as the ratio of the number of pts who retained ibrutinib treatment to the number of pts at risk. Univariate logistic regression analyses assessed the likelihood of retention rate at 1 y based on typology at BL, using the HA/HC group as a reference.

Results

Overall, 302 pts were enrolled (104 in C1, 90 in C2, 108 in C3). Median follow-up was 30.9 m (30.6 C1, 31.5 C2, 30.9 C3). BL demographics and disease characteristics are reported in Table 1. Data for typology were available for 280 pts.

Using the safety data set (N=302), at BL, 23.5% of pts reported HA/HC (28.8% C1, 18.9% C2, 22.2% C3), 20.2% HA/LC (19.2% C1, 14.4% C2, 25.9% C3), 2.0% LA/HC (1.9% C1, 2.2% C2, 1.9% C3) and 47.0% LA/LC (42.3% C1, 56.7% C2, 43.5% C3). During the first 6 m, the proportion of overall pts reporting HA/HC, HA/LC and LA/HC remained relatively consistent, whereas the proportion of pts reporting LA/LC decreased (Figure 1). At 2 y, 17.9% of pts reported HA/HC (18.3% C1, 21.1% C2, 14.8% C3), 12.6% HA/LC (12.5% C1, 15.6% C2, 10.2% C3), 0.3% LA/HC (0% C1, 1.1% C2, 0% C3) and 11.3% LA/LC (12.5% C1, 16.7% C2, 5.6% C3) (Figure 1).

Of those with documented typology at BL, at 2 y, 30.7% of pts reported high adherence (HA/HC, 43.7%; HA/LC, 31.3%; LA/HC, 0%; LA/LC, 25.4%), 10.7% medium adherence (HA/HC, 5.6%; HA/LC, 14.8%; LA/HC, 0%; LA/LC, 12.0%) and 1.4% low adherence (HA/HC, 0%; HA/LC, 1.6%; LA/HC, 0%; LA/LC, 2.1%). Pts who reported HA/HC at BL maintained a higher adherence than those who reported LA/LC.

Of those with documented typology at BL, the overall retention rate at 1 y was 70.4%. The retention rate was higher for pts who reported HA/HC (78.9%) or HA/LC (73.8%) at BL, compared with those who reported LA/HC (50.0%) or LA/LC (65.5%) at BL. Accordingly, LA/LC pts were significantly less likely to remain on treatment at 1 y compared with HA/HC pts (odds ratio=0.508; 95% confidence interval: 0.261-0.990; P=0.047).

Conclusions

Adherence at 2 y was higher for pts with a HA/HC typology than for those with a LA/LC typology at BL. Similarly, retention rates at 1 y were higher for pts with high-acceptance typologies than for those with low-acceptance typologies at BL. There was no clear trend between retention rates and control typologies at BL. Higher adherence and retention rates may therefore be possible with increased emotive support for pts with lower acceptance of disease (Bloem et al. BMC Health Serv Res 2020).

Bloem:Janssen-Cilag BV: Current Employment, Other: My chair at Nyenrode Business University is sponsored by Janssen-Cilag BV (The Netherlands). Buchholz:Janssen-Cilag: Current Employment. Vornholz:Janssen-Cilag GmbH: Current Employment. Gerhardt:Janssen: Consultancy, Other: Travel support; Pfizer: Consultancy; Novartis: Other: Travel support.