Photo Credit: Nemes Laszlo

The following is a summary of “Ibrutinib in Early-Stage Chronic Lymphocytic Leukemia: The Randomized, Placebo-Controlled, Double-Blind, Phase III CLL12 Trial,” published in the November 2024 issue of Oncology by Langerbeins et al.  

The CLL12 trial reassesses the watch-and-wait approach for early-stage chronic lymphocytic leukemia (CLL) in the context of targeted therapies. 

Researchers conducted a prospective study to assess the efficacy of ibrutinib in early-stage CLL. 

They assigned 363 asymptomatic, treatment-naïve patients with Binet stage A CLL to receive either ibrutinib (n = 182) or placebo (n = 181), with 152 low-risk patients in the watch-and-wait group. Event-free survival (EFS), progression-free survival (PFS), time to next treatment (TTNT), OS, and safety were evaluated. 

The results showed that ibrutinib significantly delayed progression to symptomatic disease (P<.001; HR, 0.276 [95% CI, 0.188 to 0.407]), but no survival benefit was observed with 26 deaths (P=.562) at a median observation time of 69.3 months, 5-year survival rates were 93.3% (95% CI, 89.3 to 97.3) in the ibrutinib group, 93.6% (95% CI, 89.5 to 97.7) in the placebo group, and 97.9% (95% CI, 95.6 to 100) in the watch-and-wait group. The estimated 10-year survival rates from diagnosis were 86.5% (95% CI, 78.7 to 94.3) for placebo, 89.8% (95% CI, 83.3 to 96.3) for ibrutinib, and 95.3% (95% CI, 91.1 to 99.4) for watch-and-wait. In the ibrutinib group, one of 12 deaths was CLL-related, compared with 4 of 14 deaths in the placebo group from CLL progression or Richter transformation. The AEs and Serious AEs occurred in 99.4% and 60% of both groups, respectively. Cardiovascular toxicity was higher in the ibrutinib group. 

They concluded that while ibrutinib delayed disease progression in early-stage CLL, no observed survival benefit, and watch-and-wait remains the standard of care. 

Source: ascopubs.org/doi/10.1200/JCO.24.00975