KEY TAKEAWAYS
- The phase 3 CLL12 trial randomly assigned treatment-naïve Binet stage A CLL patients to receive either ibrutinib or placebo in a 1:1 ratio.
- The study’s primary endpoint was met, with a significantly improved event-free survival in the ibrutinib group.
- The most common serious AEs were atrial fibrillation, pneumonia, and rash in the ibrutinib group, basal cell carcinoma, pneumonia, and myocardial infarction in the placebo group.
- Ibrutinib showed efficacy in CLL patients early, but the results do not justify changing the current standard of “watch and wait.”
Due to the lack of success shown with chemotherapy-based therapies, observation is the current standard of care (SOC) for patients with early-stage asymptomatic chronic lymphocytic leukemia (CLL). The researchers postulated that some individuals with early-stage CLL would respond favorably to ibrutinib treatment and experience superior disease control. Asymptomatic, treatment-naive individuals with Binet stage A CLL at a higher risk of progression were randomly assigned to receive either ibrutinib (n = 182) or placebo (n = 181) at a dose of 420 mg daily in phase 3, double-blind, placebo-controlled CLL12 study.
The study’s primary goal was achieved after a median follow-up of 31 months, with ibrutinib considerably extending the lives of patients without adverse events (median, not reached vs. 47.8 months; hazard ratio = 0.25; 95% confidence range = 0.14-0.43, P< .0001).
Overall, ibrutinib was no more toxic than a placebo, with both groups experiencing the same number and severity of adverse events (AEs). Afib, pneumonia, and rashes were the most prevalent severe AEs in the ibrutinib group, while basal cell carcinoma, pneumonia, and myocardial infarction were the most common in the placebo group. Modifying the research design to forbid oral anticoagulants and eliminating CYP3A4 drug-drug interactions reduced the risk of bleeding associated with ibrutinib by 33.5%. Patients with early-stage CLL and a greater risk of progression have positive responses to ibrutinib. Unfortunately, the findings do not warrant abandoning the present “watch and wait” approach.
Source: https://pubmed.ncbi.nlm.nih.gov/34758069/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02863718
Langerbeins P, Zhang C, Robrecht S, Cramer P, Fürstenau M, Al-Sawaf O, von Tresckow J, Fink AM, Kreuzer KA, Vehling-Kaiser U, Tausch E, Müller L, Eckart MJ, Schlag R, Freier W, Gaska T, Balser C, Reiser M, Stauch M, Wendtner CM, Fischer K, Stilgenbauer S, Eichhorst B, Hallek M. The CLL12 trial: ibrutinib vs. placebo in treatment-naïve, early-stage chronic lymphocytic leukemia. Blood. 2022 Jan 13;139(2):177-187. doi: 10.1182/blood.2021010845. PMID: 34758069.
