FDA Approves Ibrutinib as Front-Line Therapy in CLL

The U.S. FDA approved ibrutinib as a first-line treatment for patients with chronic lymphocytic leukemia (CLL). The approval was based on the results of the randomized, multi-center, open-label, phase III RESONATE-2 trial that compared the use of ibrutinib versus chlorambucil in 269 treatment-naïve patients (age ≥65 years) with CLL or small lymphocytic lymphoma.

In the RESONATE-2 trial, patients were randomized 1:1 to receive either:

  • Ibrutinib 420 mg orally once daily until progression or unacceptable toxicity
  • Chlorambucil on days 1 and 15 of a 28-day cycle for up to 12 cycles (starting dose was 0.5 mg/kg and increased based on tolerability in cycle 2 by increments of 0.1 mg/kg to a maximum dose of 0.8 mg/kg)

After a median follow-up of 18.4 months, ibrutinib improved progression-free survival (PFS; the study’s primary endpoint) compared with chlorambucil (not reached vs. 18.9 months; 95% CI 14.1-22.0), resulting in an 84 percent reduction in risk of progression or death (95% CI 0.091-0.283). Ibrutinib was also associated with a significantly higher overall response rate (secondary endpoint) compared with chlorambucil: 82.4 percent versus 35.3 percent (p<0.0001). Five patients in the ibrutinib cohort (3.7%) achieved a complete response compared with two patients in the chlorambucil group (1.5%).

The most common adverse events associated with ibrutinib included diarrhea, musculoskeletal pain, cough, and rash.

Ibrutinib was previously U.S. FDA-approved to treat high-risk CLL in patients with deletion of the 17p13 chromosomal region, mantle cell lymphoma in patients who have received at least one prior therapy, and Waldenström macroglobulinemia.

Source: AbbVie press release, March 4, 2016.

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