Prognostic value of patient-reported outcome thresholds on survival and adverse events in CLL/SLL: A pooled analysis of ibrutinib trials

Background EORTC thresholds for clinical importance on the QLQ-C30 have been proposed to improve the interpretability of patient-reported outcomes (PROs), but their clinical relevance remains underexplored in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Objectives This study aimed to evaluate the frequency of clinically important baseline PRO domains and their associations with survival and adverse events in patients with CLL/SLL. Design This was a pooled retrospective analysis of individual patient data from three randomized clinical trials of ibrutinib-based therapy. Methods Data were pooled from RESONATE, RESONATE-2, and HELIOS. EORTC thresholds for clinical importance were applied to baseline QLQ-C30 scores to identify clinically important PRO domains. Cox proportional hazards models were used to examine associations between the number of clinically important PRO domains and overall survival (OS), progression-free survival (PFS), and grade ≥3 adverse events. Results Among 1,238 patients, 920 (74%) reported at least one clinically important PRO domain and 395 (32%) reported five or more. Each additional clinically important domain was independently associated with worse OS (adjusted HR [95% CI]: 1.07 [1.04–1.11]; P < 0.001), worse PFS (1.03 [1.00–1.06]; P = 0.047), and increased risk of grade ≥3 adverse events (1.03 [1.01–1.06]; P = 0.006). Compared with patients reporting no clinically important PRO domains, those with ≥5 domains had worse OS (2.04 [1.42–2.94]; P < 0.001) and higher risk of grade ≥3 adverse events (1.47 [1.17–1.85]; P < 0.001). Physical function was the strongest individual prognostic domain for OS (C-index = 0.63). Conclusion Clinically important PRO domains were common among patients with CLL/SLL initiating ibrutinib-based therapy and were independently associated with survival and toxicity outcomes. These findings support the clinical utility of EORTC QLQ-C30 thresholds for identifying patients with higher baseline PRO burden who may benefit from enhanced risk stratification, supportive care, and individualized treatment planning.