Financial Toxicity, Health-Related Quality of Life, and Medication Adherence Patient-Reported Outcomes (PROs) in Patients with Chronic Lymphocytic Leukemia (CLL) on First-Line Oral Oncolytics

Introduction                   Oral oncolytic therapies (OOT) have transformed the treatment of CLL, but high costs may cause significant financial toxicity (FT) which can adversely impact patients (pts) beyond direct out of pocket costs. Associations of FT with health-related quality of life (HRQoL) and medication adherence is unknown for OOT in CLL. We performed a prospective, mixed methods longitudinal study of patient-reported outcomes (PROs) and semi-structured interviews in pts with CLL on first-line (1L) OOT.                   Methods                   Pts initiating 1L OOT for CLL at 2 academic centers received electronic PROs: FACIT-COST (significant FT &amp;lt;26), FACT-LEU for HRQoL, MARS-5 (suboptimal adherence &amp;lt;25) and PROMIS PMAS to assess medication adherence. PROs were administered at baseline, then at 3 and 6 months after enrollment. Pearson's (r) and Spearman's (⍴) correlations assessed relationships between PRO scores. Relationships between FT and baseline variables were analyzed by ANOVA. Semi-structured interviews were analyzed by rapid matrix methods.                   Results                   Forty-seven pts were enrolled: median age 66 years (range 33-86), 53% male, 9% Black, 6% Hispanic. Median time from 1L OOT initiation to enrollment: 29 days. Majority (51%) received BTK inhibitors, mostly acalabrutinib and zanubrutinib (43%); 53% received concurrent obinutuzumab. Most insurance coverage was Medicare (47%) or private insurance (45%). Majority had no copay (66%) and received grant or patient assistance program (PAP) support (57%). PRO completion rates were 100% (baseline), 85% (3 mo) and 83% (6 mo).                   Significant FT was observed in 22% (baseline), 33% (3 mo) and 28% (6 mo). Pts closer to their cancer center (r = 0.35, p = 0.048), Hispanic pts (p = 0.031), Black pts (p = 0.011), and unemployed (p = 0.032) pts had worse FT. Pts not receiving obinutuzumab had worse FT at 3 mos (p &amp;lt; .001). FT was strongly associated with inferior HRQoL at all timepoints (r = 0.64-0.58, p &amp;lt; 0.001) on all FACT-LEU domains. FT was associated with inferior medication adherence on PMAS at baseline (r = 0.31, p = 0.048), specifically the medication beliefs and knowledge domain (r = 0.30, p = 0.043).                   Suboptimal OOT adherence was observed in 34% (baseline), 39% (3 mo) and 48% (6 mo) on MARS-5. Nonadherence (MARS-5) was associated with inferior functional wellbeing at 6 mo (r = 0.40, p = 0.046). Nonadherence (PMAS) was associated with inferior social wellbeing at baseline (r = 0.38, p = 0.009) and 3 mo (r = 0.40, p = 0.02). Nonadherence measured by MARS-5 and PMAS were strongly correlated (r = 0.51, p &amp;lt; 0.001). Pts receiving obinutuzumab had better adherence on PMAS (r = 0.29, p = 0.048). There were no significant correlations with FT or adherence and having no copay or PAP support.                   The proportion of pts at least somewhat bothered by treatment side effects was 22% (baseline), 18% (3 mo) and 36% (6 mo). Overall side effect burden was not associated with FT or adherence. However, higher fatigue was associated with worse FT (⍴ = -0.29, p = 0.01). Multivariable analysis revealed that fatigue and full-time employment were associated with worse FT at 3 months (p = 0.015).                   Ten pts were interviewed. Most had no out of pocket costs aside from deductibles. Many reported uncertainty around future funding and/or losing access to PAP. OOT side effects included fatigue (most commonly), nausea, diarrhea, headaches, and weight loss. Many reported positive effects after starting OOT, including reduced lymphadenopathy and improved energy. All denied difficulty with OOT adherence, with a few reporting rare unintentionally missed doses.                   Discussion                   Pts with CLL on 1L OOT are at risk for early and progressive FT and suboptimal adherence that worsen over time. We found that FT and nonadherence are significantly associated with inferior HRQoL; assessment of these domains soon after OOT initiation is warranted to identify pts who may benefit from additional support. A significant proportion of pts reported FT and suboptimal adherence despite no copays and PAP support, suggesting these are driven by factors beyond out of pocket costs. Interview data suggest fear of losing future financial assistance may contribute to FT. Discrepancies between PRO and interview data surrounding adherence justify study of the MARS-5 and PROMIS PMAS instruments for OOT adherence assessment. Fatigue may also contribute to FT, specifically in employed pts, and future work should investigate how HRQoL and OOT-related side effects influence FT and medication adherence in CLL.