KEY TAKEAWAYS
- The phase 3 CLL12 trial evaluated ibrutinib in pts with early-stage CLL.
- Asymptomatic, treatment-naïve Binet stage A CLL pts at increased risk of progression were randomized in a 1:1 ratio to receive ibrutinib.
- Researchers aimed to evaluate EFS, PFS, TTNT, and OS during their final analysis.
- Ibrutinib administered to pts with early-stage CLL did not improve OS compared to placebo.
The phase 3, double-blind, placebo-controlled CLL12 trial evaluated the use of ibrutinib in patients with early-stage CLL. Patients (pts) with asymptomatic, treatment-naïve Binet stage A CLL at increased risk of progression were randomized in a 1:1 ratio to receive ibrutinib (n = 182) or placebo (n = 181) at 420 mg daily. A total of 152 pts with low-risk CLL were allocated to the watch and wait group (W&W). The final analysis evaluated event-free survival (EFS), progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS).
After a 69.3-month observation, the ORR was 72.5% in the ibrutinib group. PFS, EFS, and TTNT did not reach in the ibrutinib group versus 14 months (p < 0.001; HR 0.174, 95% CI 0.122–0.246), 51.6 months (p < 0.001; HR 0.276, 95% CI 0.188–0.407), and 68.5 months (p < 0.001; HR 0.244, 95% CI 0.156–0.380) in the placebo group.
A total of 29 (15.9%), 79 (43.6%), and 25 (16.4%) subsequent treatment lines were administered in the ibrutinib, placebo, and W&W group, respectively. The median overall survival was not reached in either treatment group (p = 0.562, HR 0.791, 95% CI 0.358–1.748). 12 (6.6%) deaths in the ibrutinib and 14 (7.7%) in the placebo group were documented. The 5-year estimated survival rates for patients receiving ibrutinib and placebo were 93.3% and 93.6%.
The W&W group had 3.9% death percentage, with 6 deaths and no determined median survival rate. The placebo group had a median survival rate of 258 months, while the ibrutinib group also did not have a median survival rate established.
The causes of death varied and included progressive disease (1x ibrutinib), Richter Transformation (3x placebo), treatment-related adverse event (1x ibrutinib, subdural hematoma), infection (2x ibrutinib, 1x placebo, 1x W&W), concomitant disease (4x ibrutinib, 5x placebo, 4x W&W), and other (4x ibrutinib, 5x placebo, 1x W&W).
Patients treated with ibrutinib experienced more bleeding events (36.5% vs. 14.9%), cardiac arrhythmias (22.4% vs. 9.5%), other cardiac events (17.6% vs. 15.5%), diarrhea (40.6% vs. 28.6%), and hypertensive disorders (19.4% vs. 8.3%) as compared to those who received a placebo.
Ibrutinib did not provide overall survival benefits as against placebo in the early treatment of asymptomatic Binet stage A CLL patients with a high risk of progression using. Researchers recommended that watch and wait should continue to be the standard of care for patients with early-stage CLL and inactive disease, irrespective of any genetic, laboratory, or clinical risk factors.
Source: https://onlinelibrary.wiley.com/doi/10.1002/hon.3163_24
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT02863718
Langerbeins, P., Robrecht, S., Nieper, P., Cramer, P., Fürstenau, M., Al-Sawaf, O., Fink, A., Kreuzer, K., Vehling-Kaiser, U., Tausch, E., Schneider, C., Müller, L., Schlag, R., Freier, W., Gaska, T., Balser, C., Reiser, M., Stauch, M., Zahn, M., Hallek, M. IBRUTINIB VERSUS PLACEBO IN PATIENTS WITH ASYMPTOMATIC, TREATMENT-NAïVE EARLY STAGE CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): FINAL RESULTS OF THE CLL12 TRIAL. Hematological Oncology, 41, 56-58. https://doi.org/10.1002/hon.3163_24
