ASH 2018: Ibrutinib Plus Rituximab vs Standard Chemoimmunotherapy in Younger Patients With Treatment-Naive CLL
A 6-month course of chemotherapy-based treatment with FCR (intravenous fludarabine and cyclophosphamide plus rituximab [Rituxan]) has historically been the most effective treatment for chronic lymphocytic leukemia (CLL), especially in patients 70 years of age and younger. However, results from a head-to-head phase III trial comparing FCR against a more targeted ibrutinib (Imbruvica)-based therapy showed that patients receiving ibrutinib plus rituximab had a two-thirds reduction in the risk of disease progression relative to those getting standard care. Overall survival was also significantly improved for patients receiving ibrutinib therapy, based on current follow-up. These results were presented by Shanafelt et al at the 2018 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract LBA4).
“We found ibrutinib-based therapy is both more effective and less toxic than our previous best therapy for [patients with] CLL,” said lead author Tait D. Shanafelt, MD, of the Stanford University School of Medicine, in a statement. “These findings have immediate practice-changing implications. They establish the combination of ibrutinib plus rituximab as the most effective first-line treatment for [patients with] CLL aged 70 and younger.”
Ibrutinib inhibits Bruton tyrosine kinase, a protein that is critical to the survival of CLL leukemia cells. “Ibrutinib targets the Achilles heel of CLL cells, whereas previous chemotherapy was much less targeted,” Dr. Shanafelt said.
Study Findings
The trial enrolled 529 patients with previously untreated, symptomatic CLL between January 31, 2014, and June 9, 2016. Participants ranged in age from 28 to 70 years (median age = 57). A total of 354 patients received ibrutinib plus rituximab, and 175 received a 6-month course of FCR. Researchers had tracked patient outcomes for a median of 33.4 months at the time of the analysis.
Rates of progression-free survival were significantly better in patients who received ibrutinib plus rituximab compared with FCR (hazard ratio [HR] = 0.352; 95% confidence interval [CI] =0.223-0.558; P < .0001). The hazard ratio for overall survival also favored the ibrutinib group (HR = 0.168, 95% CI = 0.053–0.538; P = .0003). In subgroup analyses for progression-free survival, ibrutinib was superior to FCR independent of age, sex, performance status, and disease stage.
Grade 3 and 4 treatment-related adverse events were observed in 58% of the ibrutinib group and 72% of the FCR-treated patients. FCR was more frequently associated with grade 3 and 4 neutropenia (44% vs 23% of the ibrutinib group) and infectious complications (17.7% vs 7% of the ibrutinib group).
Looking Ahead
Researchers will continue to monitor patients to determine the durability of these results and how they evolve over time.
“We know FCR does some collateral damage to the immune system that can be long-lasting and leave patients vulnerable to infections, whereas ibrutinib can enhance immune function,” Dr. Shanafelt said. “Understanding the long-term effects of these two therapies on the immune system and the risk of infection will be very informative.”
This federally funded study was designed by researchers with the ECOG-ACRIN Cancer Research Group under the sponsorship of the National Cancer institute (NCI), part of the National Institutes of Health. It was conducted through the NCI’s National Clinical Trials Network. E1912 is an FDA registration trial.
Disclosure: Pharmacyclics LLC provided ibrutinib and clinical trial support funding under a cooperative research-and-development agreement with the NCI and a separate agreement with ECOG-ACRIN. See the study authors’ full disclosures at ash.confex.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
