Ibrutinib Increased PFS Vs. Standard of Care in Older Patients with CLL

Treatment with ibrutinib resulted in improved progression-free survival (PFS) for older patients with chronic lymphocytic leukemia (CLL) compared with treatment with standard chemoimmunotherapy, according to the results of an international phase 3 trial presented at the 60th ASH Annual Meeting and Exposition.

At a median follow-up of 32 months, the median PFS was 41 months in patients treated with chemoimmunotherapy but has not been reached in two study arms that included ibrutinib. According to the study, CLL is a disease of older adults, with a median age of onset of about 70. Chemoimmunotherapy has become standard of treatment, with the addition of CD20 antibody to chemotherapy prolonging survival. However, although ibrutinib has been approved for untreated CLL since 2016, it has only been compared with chlorambucil and not aggressive chemoimmunotherapy.

The Alliance A041202 study, led by Jennifer A. Woyach, MD, of Ohio State University Comprehensive Cancer Center in Columbus, Ohio, evaluated ibrutinib against chemoimmunotherapy using three randomized arms:

• arm 1: the standard, aggressive chemoimmunotherapy regimen of bendamustine plus rituximab (BR)
• arm 2: ibrutinib alone
• arm 3: a combination of ibrutinib plus rituximab

The study included patients who were 65 years or older with previously untreated CLL that was symptomatic. The sample had no other significant life-limiting illnesses. The median age of the initial sample was 71 years, and 67% of the patients were men.

The eligible sample included in primary analysis was composed of 525 patients: Arm 1 = 176, Arm 2 = 178, and Arm 3 = 171. At a median follow-up of 32 months, median PFS was 41 months in Arm 1 but had not been reached in Arms 2 or 3. The researchers estimated two-year PFS to be 74% in Arm 1, 87% in Arm 2, and 88% in Arm 3. Of note, patients in Arm 1 could cross over to Arm 2 upon progression. The study had not yet found significant differences in overall survival. Median overall survival had not yet been reached in any arm.

When comparing treatment-emergent adverse events (AEs) among the three arms:

• arm 1:
  • grade 3 or higher hematologic AEs: 61%
  • grade 3 or higher non-hematologic AEs: 60%
  • grade 5 AEs: 2.8%
  • unexplained or unwitnessed death: 1.1%
• arm 2:
  • grade 3 or higher hematologic AEs: 41%
  • grade 3 or higher non-hematologic AEs: 72%
  • grade 5 AEs: 7.8%
  • unexplained or unwitnessed death: 3.9%
• arm 3:
  • grade 3 or higher hematologic AEs: 38%
  • grade 3 or higher non-hematologic AEs: 71%
  • grade 5 AEs: 7.7%
  • unexplained or unwitnessed death: 2.2%

Overall, the authors concluded that ibrutinib led to better PFS over chemoimmunotherapy in older patients with CLL, supporting its use as standard treatment. They did not find that the addition of rituximab to ibrutinib increased PFS. However, they wrote that toxicities and cost limit ibrutinib’s continuous use over the long term.