A trial found that ibrutinib in combination with bendamustine and rituximab is superior to standard of care in patients with previously treated CLL/SLL.
Dr. Chanan-Khan on the results.
A phase III trial found that ibrutinib in combination with bendamustine and rituximab is superior to bendamustine and rituximab alone in patients with previously treated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). The trial’s results (abstract LBA7005) were presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting held May 29 to June 2 in Chicago.
“CLL remains an incurable cancer, and the overarching goal of therapy continues to be disease control and prolonged remission,” said Asher A. Chanan-Khan, MD, of the Mayo Clinic in Jacksonville, Florida.
The HELIOS trial included 578 CLL/SLL patients in 21 countries; they were randomized to either ibrutinib plus bendamustine and rituximab (BR; 289 patients) or to BR plus placebo (289 patients). Patients had an average age of about 64 years, most were male, and over half had bulky disease. The median number of prior therapies was 2.0 in both groups.
The median progression-free survival (PFS) was not yet reached with the combination therapy, compared with 13.3 months in the BR and placebo group, for a hazard ratio for progression or death of 0.203 (95% confidence interval [CI], 0.150–0.276; P < .0001).
At data cutoff, 70.2% of the ibrutinib patients were still on treatment, compared with 34.6% of the placebo group. The primary reason for discontinuation was progressive disease/relapse, which occurred in 45% of the placebo group and only 4.8% of the ibrutinib group.
Chanan-Khan said that the improvement with ibrutinib was noticeable as early as 4 months into follow-up. “A subgroup analysis demonstrated consistent [improvement] in PFS toward patients randomized to receive ibrutinib,” he said; this included high-risk patients with deletion 11q.
The overall survival analysis was confounded by the fact that 90 patients (31%) crossed over to receive ibrutinib. The median overall survival had not been reached in either group, and there was still a positive trend toward benefit with ibrutinib (P = .0598).
The overall response rate was also better with ibrutinib, at 82.7% vs 67.8% with BR and placebo (P < .0001).
The toxicity profiles of the two arms were similar. The most common grade 3/4 adverse event was neutropenia, and there was a higher incidence of grade 3/4 atrial fibrillation in the ibrutinib arm (2.8% vs 0.7%). Chanan-Khan said that the etiology of this is unclear.
“This result led us to conclude that ibrutinib plus BR is superior to the current standard of care… in patients with previously treated CLL,” he said.
Lloyd Earl Damon, MD, of the University of California, San Francisco, was the discussant for the session and said that this is an important advance in this field. In the future more research will be needed on ibrutinib along with monoclonal antibody therapy, he said, to answer the question of whether chemotherapy can be safely omitted as a first-line CLL treatment.