Study suggests a survival benefit with ibrutinib compared with chemoimmunotherapy bendamustine plus rituximab in patients with chronic lymphocytic leukemia.
In older patients with untreated chronic lymphocytic leukemia (CLL), treatment with ibrutinib (Imbruvica) was found to be more effective than chemoimmunotherapy bendamustine plus rituximab, according to a new phase 3 trial.
Patients with CLL are commonly treated with the chemotherapy and immunotherapy combination bendamustine plus rituximab. Because chemoimmunotherapy is associated with a risk of toxic effects, especially in older patients, the use of an effective targeted therapy could be beneficial. The results of the trial provide support for treatment with ibrutinib as a standard of care for the disease, the study authors wrote.
Ibrutinib, which was approved by the FDA for the treatment of CLL in 2016, is an irreversible Bruton’s tyrosine kinase (BTK) inhibitor.
The study included 547 patients with CLL who were 65 years of age or older at 291 centers in the United States and Canada. Of these patients, 183 received ibrutinib plus rituximab, 182 received ibrutinib monotherapy, and 182 received bendamustine plus rituximab over a 2-year period. The median age was 71 years and 67% of the patients were men.
Overall, the data showed that progression-free survival at 2 years was 87% for patients treated with ibrutinib alone, 88% for patients treated with ibrutinib plus rituximab, and 78% for patients who received bendamustine plus rituximab. Additionally, there was no significant difference among the 3 treatment groups regarding overall survival, according to the study.
The rates of grade 3, 4, or 5 hematologic adverse events was higher in the benadmustine plus rituximab group (61%) compared with ibrutinib monotherapy or ibrutinib plus rituximab (41% and 39%, respectively). For nonhematologic events, the rate was lower in the bendamustine plus rituximab group (63%) than with the ibrutinib regimens (74% in each group). Approximately 17% of patients who received ibrutinib alone experienced atrial fibrillation, according to the data.
In all subgroups based on risk factors for CLL, progression-free survival was longer in the ibrutinib groups, but the difference was not significant among patients with ZAP70-methylated disease, the study found.
“The results of this analysis show the efficacy of treatment with continuous ibrutinib among patients with untreated CLL, but the results also raise the issue whether indefinite therapy with a BTK inhibitor is needed,” the study authors wrote.
An ongoing trial aims to conduct a similar analysis among younger adults with CLL.
Woyach JA, Ruppert AS, Heerema NA, et al. Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL. New England Journal of Medicine. 2018. Doi: 10.1056/NEJMoa1812836