Woyach JA, et al. - Experts conducted a phase 3 trial to assess the effectiveness of ibrutinib, either alone or in combination with rituximab, relative to chemoimmunotherapy in older patients with untreated chronic lymphocytic leukemia (CLL). Findings suggested superiority of treatment with ibrutinib to treatment with bendamustine plus rituximab with regard to progression-free survival among older patients with untreated CLL. Ibrutinib and ibrutinib plus rituximab did not differ significantly with regard to progression-free survival.

Methods

• Experts randomly assigned the patients 65 years of age or older who had untreated CLL to receive bendamustine plus rituximab, ibrutinib, or ibrutinib plus rituximab
• Progression-free survival was the primary end point.
• The decision to release the data was made by the Alliance Data and Safety Monitoring Board after the protocol-specified efficacy threshold had been met.

Results

• As per data, they assigned a total of 183 patients to receive bendamustine plus rituximab, 182 to receive ibrutinib, and 182 to receive ibrutinib plus rituximab.
• Findings suggested that median progression-free survival was reached only with bendamustine plus rituximab.
• Results demonstrated that the estimated percentage of patients with progression-free survival at 2 years was 74% with bendamustine plus rituximab and was higher with ibrutinib alone (87%; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.26 to 0.58; P<0.001) and with ibrutinib plus rituximab (88%; hazard ratio, 0.38; 95% CI, 0.25 to 0.59; P<0.001).
• The ibrutinib-plus-rituximab group and the ibrutinib group did not differ significantly with regard to progression-free survival (hazard ratio, 1.00; 95% CI, 0.62 to 1.62; P=0.49).
• With a median follow-up of 38 months, there was no significant difference among the three treatment groups with regard to overall survival.
• They noted higher rate of grade 3, 4, or 5 hematologic adverse events with bendamustine plus rituximab (61%) than with ibrutinib or ibrutinib plus rituximab (41% and 39%, respectively), whereas the rate of grade 3, 4, or 5 nonhematologic adverse events was lower with bendamustine plus rituximab (63%) than with the ibrutinib-containing regimens (74% with each regimen).