Understanding Clinician and Patient Preferences about Novel Agents in Chronic Lymphocytic Leukemia

Introduction: Chronic lymphocytic leukemia (CLL) is an indolent disease most common in elderly adults. While chemo-immunotherapy is a standard first-line (1L) therapy for physically fit patients, treatment options for all CLL patients have greatly increased with the approval of novel agents. Thus, treatment decision-making in CLL has become more challenging, as physicians and patients must consider the risk-benefit trade-offs inherent to treatment options. Yet, little is known about the attitudes, beliefs, and preferences that underlie treatment decision-making in real-world settings for CLL. We aimed to elucidate oncologist/hematologist (ONC) and patient (PT) preferences about key attributes associated with novel CLL treatments using qualitative methods.

Methods: In May 2019, we conducted in-depth interviews with 10 ONCs who each manage ≥20 CLL PTs with systemic therapy, prescribe novel agents for CLL, and spend at least 50% of their time in direct PT care. In addition, we interviewed 10 adult PTs with CLL. A commercial healthcare database was used to recruit ONCs, and PTs were recruited via advocacy groups. A trained moderator used a semi-structured interview guide to facilitate interviews focused on attributes influencing CLL treatment decision-making; for ONCs, interviews also asked about factors used to decide whether to treat a PT (vs. active surveillance [AS]). A standardized qualitative coding procedure (content analysis) was used to identify key themes emerging from interview responses. Descriptive statistics are reported to summarize the results.

Results: ONCs had a median of 10.5 (range: 7-30) years in practice; most (n=7, 70%) reported working in an academic setting. The decision on whether or not to initiate treatment (vs. AS) depended on multiple factors, primarily symptoms, with patient motivation, health status, and treatment goals playing a lesser role. All ONCs prioritized efficacy when selecting a CLL treatment; progression-free survival (PFS; n=9) and overall survival (OS; n=7) were the top 2 metrics considered. Shorter treatment duration was considered when preferred by the PT or where adherence was a concern. ONCs perceived novel CLL therapies to be effective and well-tolerated; tumor lysis syndrome (TLS; n=8), atrial fibrillation (n=7), and diarrhea (n=7) were among the adverse events (AEs) most often cited as being a concern. ONCs perceived dose reduction as a way to mitigate certain types of AEs. All non-academic ONCs (n=3, 100%) presented one specific treatment to their PTs, but most academic ONCs (n=5, 71%) also discussed options with PTs, even if one specific treatment was recommended.

Among PTs, the median age was 62.5 (range: 54-78) years, and most (n=7, 70%) were female. Four (40%) PTs were in 1L, with 4 (40%) in second/later lines (2L+), of treatment for their CLL; 2 (20%) PTs were in AS. Efficacy (described in terms of long-term remission) and concern about the impact of AEs on quality of life (QoL) were of greatest importance to PTs in choosing a treatment. Half reported that their ONC presented a specific recommendation for 1L treatment. Among 1L and 2L+ PTs (n=8), most (n=6, 75%) reported that ONCs did not provide detailed information about AEs associated with their CLL treatment. Across all PTs, cardiac issues and TLS (each, n=7) were the serious AEs most frequently reported as being of concern; other potential AEs, including joint pain (n=5) and brittle fingernails (n=2), were also cited as being of concern. Most PTs (n=9, 90%) expressed their preference for the convenience of oral over intravenous therapy. PTs who had a dose reduction (n=3) reported less apprehension about the potential impact on treatment efficacy than those who never had a dose reduction (n=7).

Conclusions: While there was overlap between ONCs and PTs in the most concerning AEs, some PTs cited additional AEs due to the potential impact to their QoL. Regarding treatment preferences, PTs placed high importance on the impact of AEs on QoL, although this was of less importance to ONCs. Unlike ONCs, who viewed dose reductions as a means of resolving certain AEs, some PTs tended to question whether a dose reduction would diminish treatment efficacy. A better understanding of factors that influence treatment preferences may help facilitate ONC-PT communication when selecting novel CLL therapies. Future research should verify if these findings generalize to a representative PT population.