In a German phase III trial (CLL12), reported in the Journal of Clinical Oncology, Langerbeins et al found that ibrutinib prolonged the time to symptomatic disease in patients with early-stage chronic lymphocytic leukemia (CLL) vs placebo. However, no differences in overall survival were observed.
Study Details
In the double-blind multicenter trial, 363 patients with asymptomatic, treatment-naive Binet stage A CLL at increased risk of disease progression were enrolled between May 2014 and February 2019. They were randomly assigned to receive ibrutinib at 420 mg/d (n = 182) or placebo (n = 181). An additional 152 low-risk patients were allocated to a watch-and-wait group.
Key Findings
The ibrutinib group had significantly delayed progression to symptomatic disease (hazard ratio = 0.276, 95% confidence interval [CI] = 0.188–0.407, P < .001). No survival benefit was observed in the ibrutinib group vs the placebo group (P = .562), with a total of 26 deaths being observed over a median follow-up of 69.3 months. The overall survival rate at 5 years was 93.3% with ibrutinib, 93.6% with placebo, and 97.9% in the low-risk watch-and-wait group; estimated 10-year overall survival rates were 89.8%, 86.5%, and 95.3%, respectively.
Grade ≥ 3 adverse events were reported in 71.8% of the ibrutinib group vs 66.1% of the placebo group, with the most common across both groups being atrial fibrillation (8.8% vs 2.4%) and pneumonia (4.7% vs 6.5%). Serious adverse events occurred in 60% of patients in each group. The incidence of any-grade cardiovascular toxicity was higher in the ibrutinib group.
The investigators concluded: “Ibrutinib treatment in early-stage CLL delayed disease progression compared with placebo. However, with the given observation time and few deaths, no survival benefit was demonstrated. In the era of targeted therapies, watch and wait remains the standard of care irrespective of risk factors.”
Petra Langerbeins, MD, of the Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, German CLL Study Group, Faculty of Medicine, and University Hospital Cologne, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The trial was supported by Janssen. For full disclosures of the study authors, visit ascopubs.org.
