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TOPLINE
The addition of the Bruton tyrosine kinase inhibitor acalabrutinib to bendamustine and rituximab (BR) to frontline treatment for mantle cell lymphoma (MCL) significantly reduces the risk for disease progression or death compared with BR alone. The results of the long-term analysis of the phase 3 ECHO also show greater benefits with the concurrent combination of the three-drug regimen than with the sequential addition of acalabrutinib to BR. Grade 3 or higher adverse event rates were high in both groups.
METHODOLOGY
- The analysis, which was presented by first author Michael L. Wang, MD, at the Society of Hematologic Oncology (SOHO) 2026, evaluated long-term data on 598 treatment-naive patients with MCL. The patients, who had a median age of 71 years, were participants in the original phase 3 ECHO trial.
- The study participants were treated in a 1:1 ratio (299 patients in each arm) with acalabrutinib or placebo plus BR.
- Acalabrutinib, at a dose of 100 mg twice daily, or placebo, was administered from the study commencement until either disease progression or unacceptable toxicity.
- Each group also received six cycles of bendamustine (90 mg/m2 once daily; days 1 and 2) and rituximab (375 mg/m2 as a single dose; day 1), followed by rituximab maintenance in responding patients for 2 years.
- Patients in the placebo group who developed disease progression were permitted to cross over to acalabrutinib.
TAKEAWAY
- At a median follow-up of 60.8 months (range, 0-88.5 months), the median progression-free survival was 72.5 months vs 47.8 months in the acalabrutinib group vs the placebo group (stratified hazard ratio [HR], 0.68; P = .002).
- The median overall survival was not reached in either study arm (stratified HR, 0.87).
- The median time to the need for a subsequent treatment was not reached in the acalabrutinib arm vs 73.8 months with placebo, representing a 24% reduction in the likelihood of requiring a third-line therapy with acalabrutinib (stratified HR, 0.76).
- Of those in the placebo group who received a subsequent treatment, 72% crossed over to acalabrutinib. At 48 months, the proportion of patients in the acalabrutinib arm who had not died or initiated third-line therapy was still higher than in the placebo/BR arm (including crossovers), at 67.6% vs 59.2%.
- Grade 3 or higher adverse events occurred at nearly identical rates in the acalabrutinib and placebo groups (88.9% and 88.2%, respectively). No additional toxicities or adverse events were observed with the longer duration of therapy than in the primary analysis.
IN PRACTICE
“These results emphasize the benefits of acalabrutinib plus BR as a first-line therapy approach, improving [progression-free survival] and delaying the need for subsequent therapies in patients with the treatment-naive mantle cell lymphoma,” said Wang, of The University of Texas MD Anderson Cancer Center, Department of Lymphoma/Myeloma in Houston, during his presentation at SOHO.
Overall, “the need for subsequent anticancer therapy was threefold higher with placebo/BR vs acalabrutinib/BR (33.5% vs 11.0%),” he said.
SOURCE
The study was presented at the Society of Hematologic Oncology (SOHO) 2026.
LIMITATIONS
The study was not powered for overall survival, but the results were consistent with those previously reported, with the number of events at the analysis cutoff being about 38%.
DISCLOSURES
The study was sponsored by AstraZeneca. Wang reported consulting and/or other relationships with AstraZeneca; Kite, a Gilead company; Oncternal Therapeutics; Eli Lilly and Company; InnoCare; Genmab; Boxer Capital; Galapagos NV; Pfizer; PER; Janssen; Bristol Myers Squibb; Merck; and PeproMene Bio, Inc.
