European CHMP Recommends Approval for Front-line Use of Ibrutinib for CLL

Europe’s Committee for Medicinal Products for Human Use (CHMP) has recommended ibrutinib as a single agent for front-line use in patients with chronic lymphocytic leukemia (CLL).

The CHMP opinion will be sent to the European Commission for a final regulatory decision. In Europe, ibrutinib is already approved for patients with relapsed/refractory mantle cell lymphoma and Waldenström macroglobulinemia, both as a single agent for pretreated patients and in combination with chemoimmunotherapy in the front-line setting. It is also approved for adults with CLL following one prior therapy or as front-line therapy for patients with the 17p deletion or TP53 mutation.

In March, the U.S. Food and Drug Administration approved ibrutinib for first-line treatment for patients with CLL.

The recommendation is based on the results of the open-label, international, phase III RESONATE-2 study that included 269 older patients (median age = 73 years) with CLL and small lymphocytic lymphoma and compared the use of:

  • Ibrutinib 420 mg administered once daily (n=136)
  • Chlorambucil 0.5-0.8 mg/kg on days 1 and 15 of a 28-day cycle (n=133)

Ibrutinib reduced the risk of progression or death by 84 percent compared with chlorambucil. After a median follow-up of 18.4 months, the median progression-free survival (PFS; the study’s primary endpoint) was not yet reached for those receiving ibrutinib versus 18.9 months for those in the chlorambucil cohort (hazard ratio = 0.16; 95% CI 0.09-0.28; p<.0001). The estimated 24-month overall survival rate was 98 percent for ibrutinib and 85 percent for chlorambucil. The researchers noted that PFS remained consistent across all patient subgroups, including age, Rai stage, Eastern Cooperative Oncology Group status, bulky disease, del11q mutation, and unmutated IGHV.

Three deaths occurred in the ibrutinib cohort, none of which were attributed to disease progression, while 17 deaths occurred in the chlorambucil group.

All-grade adverse events that occurred in the ibrutinib and chlorambucil cohorts included hypertension (14% vs. 0%), atrial fibrillation (6% vs. 0%), and major hemorrhage (4% vs. 2%).

Source: Janssen press release, May 1, 2016.