Ibrutinib is a first-in-class, oral, covalent inhibitor of Bruton’s tyrosine kinase that is approved for the treatment of patients with previously treated chronic lymphocytic leukemia (CLL) in patients who have received at least 1 prior therapy and in patients with the high-risk deletion 17p cytogenetic abnormality.1 The HELIOS trial is a randomized, double-blind, placebo-controlled, phase 3 trial, which demonstrated that the addition of ibrutinib to the bendamustine/rituximab (BR) regimen resulted in an 80% reduction in disease progression or death in patients with previously treated CLL/small lymphocytic leukemia (SLL).1 At ASH 2015, Chanan-Khan and colleagues reported results of subgroup analyses of this trial based on relevant high-risk prognostic factors.2
A total of 287 patients in each treatment arm were evaluable for this biomarker analysis; the HELIOS trial excluded patients with deletion 17p (>20% of cells). In the overall study population, at a median follow-up of 17 months, the progression-free survival (PFS) was significantly longer with ibrutinib plus BR versus BR (median PFS: not reached vs 13.3 months; hazard ratio [HR], 0.203; P <.0001). This PFS benefit with ibrutinib plus BR therapy also extended to the subgroup of patients with adverse prognostic factors such as del11q, complex karyotype, elevated ZAP70, and unmutated IgHV. Importantly, ibrutinib plus BR appeared to overcome the negative PFS impact of these high-risk risk factors, with median PFS of not reached reported in all risk factors assessed. By contrast, each of these adverse prognostic parameters had a negative impact on PFS in the placebo + BR arm (del11q: 11.01 months vs 13.86 months; complex karyotype: 8.5 months vs 13.8 months; unmutated IgVH: 11.3 months vs 22.1 months; elevated ZAP70: 11.37 months vs 16.43 months). Patients with del11q, unmutated IgVH, or elevated ZAP70 that were treated with ibrutinib + BR also showed statistically significant overall survival benefits compared with placebo + BR (del11q: HR, 0.326, P = .025; unmutated IgVH: HR, 0.515, P = .017; elevated ZAP70: HR, 0.536, P = .048). These results indicate that ibrutinib + BR is an active treatment option for all patients with previously treated CLL/SLL, including those with high-risk prognostic factors.
