Ahmad Y Abuhelwa, Sara A Almansour, Humaid O Al-Shamsi, Ziad Abuhelwa, Mohamad A Ziade, Yasser Bustanji, Mohammad H Semreen, Mohammad A Y Alqudah, Ross A McKinnon, Karem H Alzoubi, Michael J Sorich, Ashley M Hopkins
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.
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.