Ibrutinib versus Ofatumumab in Patients with Relapsed/Refractory CLL in the RESONATE Study
Ibrutinib was shown to impart significant PFS and OS benefits over ofatumumab as single-agent therapy in patients with relapsed or refractory CLL in the RESONATE study (Byrd JC, et al. N Engl J Med. 2014;371:213-223). At ASH 2014, Barrientos and colleagues reported a subanalysis from RESONATE in which measures of patient well-being and hematologic, immunologic, and quality-of-life (QOL) parameters were assessed (Blood. 2014;124. Abstract 4696).
A total of 391 patients with relapsed or refractory CLL were randomized to ibrutinib or to ofatumumab for up to 24 weeks; in this subanalysis, assessments included sustained hematologic improvement of ?56 days without transfusions or growth factors, outcomes on the FACIT-Fatigue Scale, disease-related symptoms, serum immunoglobulin, patient-reported outcomes by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 scale (a questionnaire developed to assess the QOL of patients with cancer), and medical resource utilization.
In the ibrutinib arm, 69% of patients with baseline cytopenias experienced sustained improvement in blood counts compared with 43% of patients receiving ofatumumab (P <.001). Immunoglobulin A levels increased in the ibrutinib arm only. At week 24, a clinically meaningful mean change in FACIT-F score from baseline occurred in 59% of ibrutinib-treated patients versus in 46% of patients receiving ofatumumab (P = .06). Moreover, a larger proportion of patients receiving ibrutinib than ofatumumab showed clinically meaningful improvement on the EORTC QLQ-C30 global health scores scale (46% vs 40%, respectively). Ibrutinib-treated patients also demonstrated significantly better outcomes in terms of fatigue, reduction in lymph nodes, and spleen size compared with patients receiving ofatumumab, as well as abatement of leukemia-associated symptoms (eg, weight loss, night sweats, and anorexia). Hospitalizations in the first 30 days occurred in 2% of patients receiving ibrutinib and in 15% receiving ofatumumab. The AEs for the 2 groups were as previously reported, but there was a 43% relative reduction for grade 3/4 infections in the ibrutinib group.
The authors conclude that, compared with ofatumumab, ibrutinib administered to patients with relapsed or refractory CLL leads to improvements in hematologic function and disease burden. These sustained improvements in hematologic end points and patient-reported outcomes, coupled with the OS benefit previously reported for ibrutinib (Byrd JC, et al. N Engl J Med. 2014;371:213-223), suggest that ibrutinib enhances QOL while prolonging survival in these patients.