ASH 2018 — Frontline ibrutinib tops chemoimmunotherapy for CLL in older patients

Study design

• International phase 3 trial of 547 patients aged ≥65 years with newly diagnosed CLL, randomly assigned to:
  • bendamustine, 90 mg/m², on days 1 and 2 of each 28-day cycle plus rituximab, 375 mg/m², on day 0 of cycle 1, then 500 mg/m² on day 1 of cycles 2-6; 
  • ibrutinib, 420 mg/day, until disease progression; or
  • ibrutinib, 420 mg/day, until progression, plus rituximab, 375 mg/m², weekly for 4 weeks starting on day 1 of cycle 2, then day 1 of cycles 3-6
• Funding: National Cancer Institute; NIH.

Key results

• 2-year estimates for PFS were 74% (95% CI, 66-80%) for bendamustine+rituximab, 87% (95% CI, 81%-92%) for ibrutinib alone, and 88% (95% CI, 81%-92%) for ibrutinib+rituximab.
• Thus far, OS does not differ between groups (P=.87); median OS has not been reached in any group.
• 2-year OS survival estimates for bendamustine+rituximab, ibrutinib alone, and ibrutinib+rituximab are 95%, 90%, and 94%, respectively
• Grade 3-5 nonhematologic events including atrial fibrillation and hypertension occurred significantly more often in ibrutinib-containing groups. Grade 3-5 hematologic events were significantly more likely in the bendamustine-rituximab group.

Limitations

• Study does not address whether ibrutinib would need to be continued indefinitely.

Expert comment

• "This really does indicate that ibrutinib as frontline therapy, which many clinicians have been doing, is a very reasonable practice," said David Steensma, MD, Dana-Farber Cancer Institute, Boston, Massachusetts.