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


  • Wayne Kuznar
  • Univadis
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Takeaway

  • Frontline ibrutinib with/without rituximab achieves significantly longer PFS than standard chemoimmunotherapy in older patients with chronic lymphocytic leukemia (CLL).

Why this matters

  • Older patients have been underrepresented in clinical trials of therapies for CLL.
  • Standard therapies in this population include chlorambucil+obinutuzumab and bendamustine+rituximab.

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.