The study began with 529 patients, all with previously untreated CLL. A total of 354 patients, all 70 years or younger, were randomly assigned to receive ibrutinib-rituximab treatment, consisting of 1 cycle of ibrutinib, followed by 6 cycles of ibrutinib-rituximab combined, and then ibrutinib alone, taken indefinitely until disease progression. The 175 patients in the control group received 6 cycles of FCR chemoimmunotherapy. The primary end point was progression-free survival (PFS), with overall survival (OS) as the secondary end point.
Patients in the ibrutinib-rituximab group received 1 dose of 420 mg per day of ibrutinib during day 1 to day 28 of each of the 6 cycles, until either their disease progressed or the side effects became intolerable. Alongside this dosage, they also received rituximab, during cycles 2 through 7. The FCR group received 6 cycles of FCR.
At a median follow-up of 33.6 months, Dr Shanafelt and the team found a benefit for the experimental treatment. At that point, 89.4% of patients in the experimental group had experienced no disease progression, compared with 72.9% in the control group. OS rates echoed the benefit: 98.8% of patients in the experimental group were still alive, compared with 91.5% of patients in the control group.
The researchers wondered if treatment efficacy would be different for patients with the IGHV-mutated CLL. Dividing the existing patients into 2 subgroups, they found that for patients carrying the mutation, the 2 protocols were nearly identical — and in fact, FCR proved 0.3% more effective. For those without the mutation, however, the ibrutinib-rituximab combination was superior to FCR: with 90.7% PFS at 3 years, compared with 62.5%, respectively. Patients in the experimental group without IGHV-mutated disease also experienced fewer serious infections.
Researchers concluded that treatment with ibrutinib-rituximab was superior to FCR with regard to both PFS and OS. They reported a 65% lower risk of progression and an 83% lower risk of death. This superior PFS was also present in high-risk subgroups, including patients with Rai stage III or stage IV disease, chromosome 11q22.3 deletion, and unmutated IGHV.