EHA 2019: CLL12 Trial Investigates Ibrutinib in Previously Untreated, Asymptomatic Early-Stage CLL
At the 24th Annual Congress of the European Hematology Association (EHA), Langerbeins et al presented findings from the phase III CLL12 trial, which evaluated whether ibrutinib prolongs event-free survival in patients with previously untreated, Binet stage A chronic lymphocytic leukemia (CLL) (Abstract LB2602). The Binet staging system, used more widely in Europe, defines stage A as disease in which fewer than three areas of lymphoid tissue are enlarged, with no anemia or thrombocytopenia.
Patients with intermediate, high, or very high risk of disease progression were randomly assigned 1:1 to receive 420 mg of either ibrutinib or placebo daily. A total of 182 or 181 patients were assigned to receive ibrutinib or placebo, respectively.
The primary endpoint was event-free survival, defined as time from randomization until occurrence of active disease according to International Workshop on CLL guidelines, new treatment, or death.
Results
At a median observation time of 31 months, event-free survival was 47.8 months in the placebo arm vs not reached in the ibrutinib arm (hazard ratio [HR] = 0.25, 95% confidence interval [CI] = 0.14–0.43; P < .0001). Progression-free survival was 14.8 months in the placebo arm vs not reached in the ibrutinib arm (HR = 0.18, 95% CI = 0.12–0.27).
Time to next treatment was longer in the ibrutinib arm. Event-free survival, progression-free survival, and time to next treatment were consistent across all risk groups, except for very high–risk patients (due to small numbers).
Adverse Events
Six deaths were reported in the ibrutinib group vs five in the placebo group. All-grade adverse events occurred in 82.2% of patients in the ibrutinib group and 84.8% of the placebo group. The most commonly reported serious adverse events were infection (11.4% of the ibrutinib group, 11.8% of the placebo group) and cardiac disorders (8.6% vs 6.7%). Adverse events of clinical interest were mostly of Common Terminology Criteria for Adverse Events grade 1–2 and significantly more frequent in the ibrutinib group.
The authors concluded, “The results of this study allow [us] to conclude that ibrutinib significantly improves event-free survival, progression-free survival, and time to next treatment in patients with treatment-naive early-stage CLL when compared to placebo. There were no significant differences in adverse events between both study arms.”
Disclosure: For full disclosures of the study authors, visit library.ehaweb.org.
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