Integrating patient and clinician perspectives to advance R/R CLL care: Results of a multi-pronged global initiative

Abstract

Abstract Background: The introduction of covalent BTK inhibitor (cBTKi) therapy and time-limited (TL) BCL2 inhibitor (BCL2i) regimens has established multiple innovative standards of 1L care for chronic lymphocytic leukemia (CLL). The development of non-covalent BTKi (ncBTKi) has similarly informed protocols for sequential care based on prognostic factors, treatment history, comorbid conditions, and patient preferences for treatment. These options have been integrated into practice guidelines in Europe and the United States for 1L and relapsed/refractory (R/R) settings (Eichhorst B et al. Ann Oncol. 2024;35:762-768; NCCN Clinical Practice Guidelines in Oncology. CLL/SLL. Version 3.2025). Despite these developments, many hematology-oncology professionals across global regions are not prepared to implement modern treatment plans informed by the latest evidence and principles of shared decision-making (Jain N et al. Leuk Lymphoma. 2025;66:1400-1412; Owen C et al. EHA 2025. Abstract PF586). We assessed the readiness of clinicians in Europe and the United States to adopt comprehensive care models through a series of educational interventions. Methods:A multi-format educational program was developed in collaboration with the CLL Society to assess and improve clinical readiness for the sequential management of R/R CLL, with an emphasis on integrating targeted therapy in different LoT. The curriculum included an online global survey of patients with R/R CLL (N = 219; conducted March-May 2025), followed by live (in-person and virtual) symposia primarily developed for hematologists and hematologist-oncologists (N = 731) that featured patient survey data, clinical evidence, interactive case discussions, and guideline-based algorithms. Learners completed pre- and post-assessments to evaluate changes in knowledge, skills, and attitudes toward sequential treatment planning. Outcomes were analyzed in aggregate across formats. Results: The global survey provided insights into the treatment experience of patients; 65% reported that their healthcare team provided consistent guidance and encouragement, but 27% noted decreased support during later lines of care. Patients cited worries over the next step in treatment as their most common concern after relapse (46%); patients also identified safety/tolerability (72%), QOL (66%), long-term efficacy (68%), and treatment location (40%) as important factors related to healthcare team treatment planning. Among healthcare professionals, participation in the curriculum was associated with improvements in knowledge and clinical decision-making related to sequential care in R/R CLL. Recognition of ncBTKi as an appropriate treatment across multiple R/R scenarios increased by 34 percentage points (46% pre vs 80% post activity; P < .05). These shifts were noted in the settings of BTKi- and BCL2i-refractory CLL (49% to 72%; P < .05) and BTKi intolerance (23% to 47%; P < .05). Attitudinal shifts toward BTK resistance testing were also notable, as the intention to consider resistance testing to complement decisions in the wake of clinical progression rose from 24% to 62% (P < .05), while uncertainty in this area declined from 44% to 19%. Exposure to patient survey data also increased the proportion of learners who sought to engage with patients when making decisions for post-cBTKi treatment (68% vs 95%; P < .05) or addressing symptoms flagged as important by patients (67% vs 90%; P < .05). Improvements were consistent across both live and enduring formats, underscoring the global scalability and clinical relevance of the intervention. Overall, these trends were largely consistent between European and US learners. Conclusions: Initiatives developed in collaboration with clinical experts and patient advocacy groups can impact real-world care by fostering adoption of patient-centered sequential care strategies in CLL. Learners demonstrated enhanced understanding of guideline- and evidence-based CLL management and increased readiness to engage proactively with patients when developing treatment plans. These outcomes suggest that globally distributed, team-based education—particularly when informed by patient perspectives and aligned with practice-changing evidence and guideline updates—can address practice gaps in CLL care.