Ibrutinib does not improve overall survival (OS), when compared to placebo, in patients with treatment-naïve chronic lymphocytic leukemia (CLL) at high risk of progression, according to research presented at the EHA 2023 Hybrid Congress.

These results, from the phase 3 CLL12 trial, showed that ibrutinib improved event-free survival (EFS) and progression-free survival (PFS) but did not improve OS.

The trial (ClinicalTrials.gov Identifier: NCT02863718) included 363 CLL patients with an increased risk of progression. The patients were randomly assigned to receive ibrutinib (n=182) or placebo (n=181). Baseline characteristics were well balanced between the arms. 

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The median follow-up was 69.3 months. The median number of treatment cycles received was 39 in the ibrutinib arm and 27.5 in the placebo arm. The rate of treatment discontinuation was 4.8% and 48.5%, respectively.

The overall response rate was 72.5% in the ibrutinib arm and 5% in the placebo arm. There was 1 complete response in the ibrutinib arm.

The median EFS was not reached in the ibrutinib arm and was 51.6 months in the placebo arm (hazard ratio [HR], 0.276; 95% CI, 0.188-0.407; P <.001). The 5-year EFS rate was 78.2% and 48.0%, respectively.

The median PFS was not reached in the ibrutinib arm and was 14.0 months in the placebo arm (HR, 0.174; 95% CI, 0.122-0.246; P <.001). The 5-year PFS rate was 73.9% and 23.7%, respectively.

The proportion of patients who received subsequent treatment was 15.9% in the ibrutinib arm and 43.6% in the placebo arm. Most patients received targeted drugs (48.3% and 45.6%, respectively) or chemoimmunotherapy (48.3% and 53.2%, respectively).

The median OS was not reached in either arm (HR, 0.791; 95% CI, 0.358-1.748; P =.562). The 5-year OS rate was 93.3% in the ibrutinib arm and 93.6% in the placebo arm. From diagnosis, the 10-year OS rate was 89.8% and 86.5%, respectively.

The rate of adverse events (AEs) was the same in both arms, at 99.4%. The rate of serious AEs was 9.9% in the ibrutinib arm and 14.9% in the placebo arm. The rate of second malignancies was 12.9% and 21.4%, respectively.

Ibrutinib was associated an increase in bleeding and cardiovascular toxicity. The rate of bleeding was 36.5% in the ibrutinib arm and 14.9% in the placebo arm. The rate of cardiac arrhythmias was 22.4% and 9.5%, respectively.

Disclosures: This research was partly supported by Janssen. No other disclosures were provided.


Langerbeins P, Robrecht S, Nieper P, et al. Ibrutinib versus placebo in patients with asymptomatic, treatment-naïve early stage chronic lymphocytic leukemia (CLL): Final results of the phase 3, double-blind, placebo-controlled CLL12 trial. EHA 2023. June 8-11, 2023. Abstract S200.

This article originally appeared on Cancer Therapy Advisor