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A significant reduction in the risk of disease progression or death resulted from treatment with acalabrutinib combined with bendamustine/rituximab (BR) in patients with previously untreated mantle cell lymphoma, according to an update from the phase 3 ECHO trial.
The updated analysis results were presented in a poster at the 66th American Society of Hematology Annual Meeting & Exposition. The purpose of the analysis was to outline PFS in the subgroup population of the study, and show minimal residual disease (MRD) data and safety findings.
The cohort comprised 598 patients with previously untreated MCL who were randomized in the study to receive the acalabrutinib combination (n=299) or placebo (n=299). At baseline, high-risk simplified MIPI score was in 24.1% of the acalabrutinib combination arm and 24.4% of the placebo arm, blastoid histology was in 8.7% and 6.7%, and pleomorphic histology was in 5.0% and 6.0%, respectively. A Ki-67 ≥30% was shown in 46.5% of the acalabrutinib arm at baseline and 49.2% of the placebo arm. Finally, baseline TP53 mutations were seen in 7.4% and 9.7%, respectively.
Among patients treated with acalabrutinib plus BR, the median PFS was 22.2 months for those who discontinued acalabrutinib during induction due to progressive disease (PD) or death and 29.4 months among those who discontinued acalabrutinib in the maintenance setting. Median PFS was not reached among acalabrutinib-treated patients who received 31 cycles or more of acalabrutinib.
According to investigators, the PFS benefits across the subgroups were consistent with the general study population.
In patients who were MRD negative in the acalabrutinib/BR arm at the end of induction therapy (week 24), 5.85% converted with MRD-positive during maintenance therapy compared with 15% of the placebo arm. Contrarily, among patients who were MRD positive at the end of induction therapy, conversion to MRD negativity was observed in 37.5% of the acalabrutinib/BR arm versus 20% of the placebo arm.
“The MRD resolutions confirm the superiority of the acalabrutinib containing study arm in more detail. Moreover, the Forrest plot confirms the superiority also in high-risk patients,” lead study author Martin H. Dreyling, MD, PhD, professor of Medicine at Klinikum der Ludwig-Maximilian-Universität München, told Blood Cancer Today.
The median exposure to acalabrutinib was 28.6 months compared with 24.6 months on placebo. Overall, the incidence of adverse events (AEs) was similar between the acalabrutinib/BR and placebo arms during induction therapy, but during maintenance therapy, AEs occurred at a higher incidence in the acalabrutinib/BR arm.
Grade ≥3 serious treatment-emergent AEs occurred in 32.6% of the acalabrutinib/BR arm versus 29/3% of the placebo arm, and grade 5 TEAEs were seen in 4.2% versus 4.0%, respectively. TEAEs led to discontinuation of treatment in 15.5% of the acalabrutinib/BR arm versus 12.4% of the placebo arm.
Based on these findings, investigators concluded that acalabrutinib in combination with BR offers clinical benefit without extreme toxicity for patients with MCL and high-risk features being treated in the front-line setting.
“Once the combination is registered, it will probably be broadly applied in elderly patients,” said Dr. Dreyling.
REFERENCE
Dreyling M, Mayer J, Belada D, et al. High-risk subgroups and MRD: An updated analysis of the phase 3 ECHO trial of acalabrutinib with bendamustine/rituximab in previously untreated mantle cell lymphoma. Presented at: 66th American Society of Hematology Annual Meeting & Exposition; December 7-10, 2024; San Diego, CA. Abstract 1626