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In Leukemia on 8th June 2017, Jennifer R. Brown from the Dana-Farber Cancer Institute, Boston, MA, USA, and colleagues published extended 19-month follow-up data and the impact of high-risk prognostic factors in patients with R/R CLL/SLL in the phase III RESONATE trial (NCT01578707).
RESONATE was a randomized, multicenter, open-label study comparing ibrutinib with ofatumumab. At the time of this updated analysis, 123 patients originally randomized to ofatumumab crossed-over to ibrutinib. PFS, OS, and other updated efficacy measures were evaluated by investigator assessment.
Patient characteristics and disposition
Safety with ibrutinib
During this 2-year follow-up of the RESONATE study, it was observed that the efficacy of ibrutinib still remained high, with nearly three-quarters (74%) of patients remaining alive and progression-free. Furthermore, tolerability was well maintained. The authors concluded that, due to a lack of PFS events, the follow-up is too short to determine if different subgroups of patients characterized by high-risk mutations have poorer PFS. It was noted that PFS seemed better in patients who developed lymphocytosis compared to those who did not. Overall, most patients “continue to do extremely well, underscoring the significant impact of ibrutinib in altering the course of relapsed CLL.”
During iwCLL 2017, Thomas J. Kipps, MD, PhD, from the University of California, San Diego, Moores Cancer Center, California, USA, gave an abstract presentation on pooled data from RESONATE, RESONATE-2, and HELIOS trials assessing the outcomes of ibrutinib-treated CLL patients with high-risk characteristics; read more here.
In the phase 3 RESONATE study, ibrutinib demonstrated superior progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) compared with ofatumumab in relapsed/refractory CLL patients with high-risk prognostic factors. We report updated results from RESONATE in these traditionally chemotherapy resistant high-risk genomic subgroups at a median follow-up of 19 months. Mutations were detected by Foundation One Heme Panel. Baseline mutations in the ibrutinib arm included TP53 (51%), SF3B1 (31%), NOTCH1 (28%), ATM (19%) and BIRC3 (14%). Median PFS was not reached, with 74% of patients randomized to ibrutinib alive and progression-free at 24 months. The improved efficacy of ibrutinib vs ofatumumab continues in all prognostic subgroups including del17p and del11q. No significant difference within the ibrutinib arm was observed for PFS across most genomic subtypes, although a subset carrying both TP53 mutation and del17p had reduced PFS compared with patients with neither abnormality. Reduced PFS or OS was not evident in patients with only del17p. PFS was significantly better for ibrutinib-treated patients in second-line vs later lines of therapy. The robust clinical activity of ibrutinib continues to show ongoing efficacy and acceptable safety consistent with prior reports, independent of various known high-risk mutations.
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