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CN4 Patient-Reported Outcomes from the Phase 3, Randomized Study of Acalabrutinib with or without Obinutuzumab Versus Chlorambucil PLUS Obinutuzumab for Treatment-Naïve Chronic Lymphocytic Leukemia (ELEVATE-TN)

      Objectives

      Report patient-reported outcomes of fatigue and health-related quality of life (HRQoL) from the randomized, phase 3, ELEVATE-TN study (NCT02475681) in patients with treatment-naïve chronic lymphocytic leukemia (CLL).

      Methods

      Patients received acalabrutinib alone (A), A plus obinutuzumab (AO), or chlorambucil plus obinutuzumab (CO). Assessments included the FACIT-Fatigue Global Fatigue Score (GFS) (scale: 0–52; lower score=worse outcome [clinically meaningful improvement: ≥+3]) and the EORTC QLQ-C30 Global Health Status (GHS) score (scale: 0–100; lower score=worse HRQoL [clinically meaningful improvement: >+8]) in all patients (excluding those who progressed) and those with severe fatigue at baseline (GFS ≤34), analyzed using mixed-model repeated measures methodology. A post-hoc analysis assessed time to clinically meaningful deterioration (TTD; change ≤−3) in GFS.

      Results

      Among 535 randomized patients, 449 completed the GFS (A, n=156; AO, n=152; CO, n=141) and 450 completed the GHS (A, n=157; AO, n=151; CO, n=142) at baseline. Overall, 151 randomized patients had severe fatigue (A, n=56; AO, n=53; CO, n=42); all completed both questionnaires at baseline. In all arms, GFS and GHS improvements were observed by week 4 (mean changes: 2.76 and 5.35 for A [n=136, n=137], 2.33 and 2.17 for AO [n=138, n=138], 1.26 and 2.53 for CO [n=121, n=122]) and maintained at 96 weeks (4.94 and 7.01 for A [n=81, n=82], 3.91 and 5.25 for AO [n=92, n=92], 3.86 and 2.41 for CO [n=38, n=38]); this benefit was larger in patients with severe fatigue. Median TTD in fatigue was longer in acalabrutinib-containing arms (A: 16.9 mo; AO: 16.7 mo) versus CO (5.7 mo [P=0.0376 vs A; P=0.1596 vs AO]).

      Conclusions

      In ELEVATE-TN, all treatments improved fatigue scores; TTD of fatigue was significantly longer with acalabrutinib-containing treatment. The previously reported statistically significant progression-free survival increases with A/AO versus CO (Lancet. 2020;395:1278-91) were accompanied by clinically meaningful HRQoL benefits.