Ibrutinib versus Ofatumumab in Previously Treated Chronic Lymphoid Leukemia

Abstract

Background In patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL), a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome. We evaluated the efficacy of ibrutinib, a covalent inhibitor of Bruton’s tyrosine kinase, in patients at risk for a poor outcome. Methods In this multicenter, open-label, phase 3 study, we randomly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab. The primary end point was the duration of progression-free survival, with the duration of overall survival and the overall response rate as secondary end points. Results At a median follow-up of 9.4 months, ibrutinib significantly improved progression-free survival; the median duration was not reached in the ibrutinib group (with a rate of progression-free survival of 88% at 6 months), as compared with a median of 8.1 months in the ofatumumab group (hazard ratio for progression or death in the ibrutinib group, 0.22; P<0.001). Ibrutinib also significantly improved overall survival (hazard ratio for death, 0.43; P = 0.005). At 12 months, the overall survival rate was 90% in the ibrutinib group and 81% in the ofatumumab group. The overall response rate was significantly higher in the ibrutinib group than in the ofatumumab group (42.6% vs. 4.1%, P<0.001). An additional 20% of ibrutinib-treated patients had a partial response with lymphocytosis. Similar effects were observed regardless of whether patients had a chromosome 17p13.1 deletion or resistance to purine analogues. The most frequent nonhematologic adverse events were diarrhea, fatigue, pyrexia, and nausea in the ibrutinib group and fatigue, infusion-related reactions, and cough in the ofatumumab group. Conclusions Ibrutinib, as compared with ofatumumab, significantly improved progression-free survival, overall survival, and response rate among patients with previously treated CLL or SLL. (Funded by Pharmacyclics and Janssen; RESONATE ClinicalTrials.gov number, NCT01578707.)

Evaluation of 230 patients with relapsed/refractory deletion 17p chronic lymphocytic leukaemia treated with ibrutinib from 3 clinical trials

“…This analysis only included patients with R/R CLL from PCYC‐1102/1103. PCYC‐1112 (NCT01578707; RESONATE) was a multi‐institutional, phase 3 study of ibrutinib versus ofatumumab in patients with R/R CLL (Byrd et al , 2014). PCYC‐1117 (NCT01744691; RESONATE‐17) was a multi‐institutional, phase 2 study of single‐agent ibrutinib in patients with R/R CLL or SLL with del(17p) (O'Brien et al , 2016a).…”

“…To provide a more robust description of outcomes in the prospective trials in this important high‐risk patient population, we conducted a combined analysis of 243 patients with R/R del(17p) CLL who received treatment with single‐agent ibrutinib (420 mg) in 1 of 3 prospective clinical studies (Byrd et al , 2013, 2014, 2015; O'Brien et al , 2014, 2016a). This analysis characterizes disease‐specific and overall survival (OS) outcomes among these patients, and describes the results of exploratory analyses conducted to better identify factors associated with variation in survival of patients with this aggressive subtype of CLL.…”

EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia

“…Although treatment has undergone profound improvements in recent years [4][5][6] , CLL shows a remarkable clinical variability which is likely to be reflective of a large biological heterogeneity 7,8 .…”

PHEDRA: using real-world data to analyze treatment patterns and ibrutinib effectiveness in hematological malignancies

“…Despite the availability of a range of RCTs investigating the treatment of these diseases, there is still a lack of comparative evidence on treatment selection, duration of treatment and disease outcomes across different lines of therapy. Since ibrutinib is relatively new to the market (first US FDA approval in 2013 and European Medicines Agency [EMA] approval in 2014), head-to-head comparisons of ibrutinib versus other widely used treatments in CLL, MCL and WM are limited (outside the RCTs used for approval) [8][9][10], and although there are growing RWD for ibrutinib, comparative effectiveness studies using RWD only are yet to reach optimal data volume and quality.…”