Background: Acalabrutinib is a potent, highly selective Bruton tyrosine kinase inhibitor approved for chronic lymphocytic leukemia (CLL) and previously treated mantle-cell lymphoma. In the pivotal ELEVATE-TN study, acalabrutinib (± obinutuzumab) demonstrated significant improvements in progression-free survival (PFS) versus chemoimmunotherapy in treatment-naive (TN) CLL after a median follow-up of 28.3 months.1 Patient-reported outcomes (PRO) data from ELEVATE- TN are reported here using the same data cutoff as the primary efficacy results.
Objective: Report PRO of fatigue and health-related quality of life (HRQoL) from the randomized, phase 3, ELEVATE-TN study (NCT02475681) in patients with TN 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 = .0376 vs A; P = .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 PFS increases with A/AO versus CO were accompanied by clinically meaningful HRQoL benefits.
- Sharman JP, Egyed M, Jurczaket W, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Lancet. 2020;395:1278-1291.