FRONTLINE treatment with acalabrutinib (Calquence) combined with bendamustine and rituximab (Rituxan; BR) has shown promising results in reducing disease progression and death in older patients with mantle cell lymphoma (MCL). This combination therapy led to a 27% reduction in the risk of disease progression or death compared to BR alone. The findings from the phase III ECHO trial were presented at the 2024 European Hematology Association (EHA) Congress.
The trial comprised 598 treatment-naïve MCL patients, randomized to receive either bendamustine and rituximab plus acalabrutinib or bendamustine and rituximab plus a placebo. The median follow-up was 45 months. Results showed that the median progression-free survival (PFS) for the acalabrutinib plus BR group was 66.4 months, compared to 49.6 months for the BR and placebo group (stratified hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.57-0.94; p = .0160).
The overall response rate (ORR) was higher in the acalabrutinib plus BR group (91.0%) compared to the BR and placebo group (88.0%). Additionally, the acalabrutinib group had a higher complete response (CR) rate (66.6% vs. 53.5%). While the median overall survival (OS) was not reached in either group, there was a trend towards improved OS in the acalabrutinib group. The safety profile of the acalabrutinib plus BR regimen was consistent with previous studies. Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 88.9% of patients in the acalabrutinib group and 88.2% in the placebo group. Serious adverse events included atrial fibrillation, hypertension, major bleeding, infections, and second primary malignancies. COVID–19–related adverse events were also noted, with higher rates in the acalabrutinib group.
Lead study author Michael Wang, University of Texas MD Anderson Cancer Center, US, presented these findings at EHA and emphasized their significance, noting that ECHO is the first trial to show a positive trend in OS with the addition of a BTK inhibitor to frontline chemoimmunotherapy in older MCL patients. In conclusion, the ECHO trial demonstrates that adding acalabrutinib to bendamustine and rituximab improves PFS in older MCL patients, potentially establishing a new standard for frontline therapy in this patient population. However, further research is warranted to confirm these findings and explore this combination therapy’s long-term benefits.
Reference:
Wang ML et al. Acalabrutinib plus bendamustine and rituximab in untreated mantle cell lymphoma: results from the phase 3, double-blind, placebo-controlled ECHO trial. Abstract LB3439. EHA Annual Meeting, 13-16 June, 2024.
