Novel CLL12 Study Investigates Outcomes With Ibrutinib in Early-Stage CLL

By: Vanessa A. Carter, BS
Posted: Tuesday, January 21, 2025

The CLL12 study, conducted by Petra Langerbeins, MD, of the University of Cologne, Germany, and colleagues, is reportedly the first trial to evaluate the efficacy and safety of the tyrosine kinase inhibitor ibrutinib in early-stage chronic lymphocytic leukemia (CLL). The results of this trial, published in the Journal of Clinical Oncology, suggest that ibrutinib has the potential to delay disease progression compared with placebo in this patient population.

“Although survival outcomes for early-stage CLL have relevantly improved compared with historical data, this enhancement is not specifically attributed to early ibrutinib intervention,” the study authors concluded. “The study underscores that, despite targeted drugs, watch and wait remains the standard of care for early-stage CLL.”

This double-blind, placebo-controlled, phase III trial enrolled 363 patients with treatment-naive, asymptomatic, Binet stage A CLL who were at an increased risk of disease progression. Participants were randomly assigned 1:1 to receive 420 mg of daily ibrutinib (n = 182) or placebo (n = 181). An additional 152 patients with low-risk disease were assigned to the “watch-and-wait” group; these patients did not receive any intervention.

At the median observation time of 69.3 months, there was no survival benefit with ibrutinib, as evidenced by 26 cases of death. However, ibrutinib significantly delayed disease progression to symptomatic disease (P < .001). Of note, the 5-year survival rates were highest in the watch-and-wait cohort (97.9%), followed by the placebo (93.6%) and ibrutinib (93.3%) cohorts; the estimated 10-year survival rates were 95.3%, 86.5%, and 89.8%, respectively.

Of 12 deaths in the ibrutinib arm, just one was associated with CLL. In the placebo group, however, 4 of 14 deaths were attributable to CLL progression or Richter transformation. Adverse events were reported in 99.4% of all patients, with serious adverse events affecting 60%. Furthermore, patients in the ibrutinib group were found to be more likely to experience cardiovascular toxicity than those on placebo.

Disclosure: For full disclosures of the study authors, visit ascopubs.org.

Journal of Clinical Oncology