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