Multicenter phase 3 trial of ibrutinib versus placebo for early-stage chronic lymphocytic leukemia

The multicenter phase 3 CLL12 trial in Germany randomized patients with asymptomatic treatment-naïve Binet Stage A CLL at increased risk of progression to receive ibrutinib at a daily dose of 420 mg (n=182) or placebo (n=181). Additionally, 152 low-risk patients were allocated to a watch-and-wait group. Ibrutinib significantly delayed progression to symptomatic disease (HR 0.276; p<0.001) but did not result in significant overall survival benefit, with after median 69.3 months of follow-up 12 deaths in the ibrutinb group and 14 deaths in the placebo group (p=0.562). In the ibrutinib group, one of 12 deaths was CLL-associated, compared with four of 14 in the placebo group. Five-year survival rates were excellent with 93.3% in the ibrutinib group as compared with 93.6% in the placebo group and 97.9% in the watch-and-wait group. The authors conclude that in the era of targeted therapies, watch-and-wait remains the standard of care for early-stage CLL irrespective of risk factors.