Long-Term ECHO Data Support Concurrent Acalabrutinib/BR in MCL

Michael Wang, MD, professor at The University of Texas MD Anderson Cancer Center, details the rationale for a long-term analysis of the phase 3 ECHO trial (NCT02972840) and highlights practical implications of its results, which were recently presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition.¹

The global ECHO trial, initiated in 2017, evaluated the combination of the Bruton tyrosine kinase (BTK) inhibitor acalabrutinib (Calquence) plus bendamustine and rituximab (Rituxan; BR) vs placebo plus BR in previously untreated older patients with mantle cell lymphoma (MCL). Primary ECHO data underpinned approval of the regimen in the US and Europe, shifting the standard of care from BR to acalabrutinib plus BR triplet therapy, with all agents administered simultaneously.

“Over the years, I have seen a lot of community doctors [who are] already embracing this combination and using them in daily practice,” Dr Wang noted during the interview.

Despite widespread adoption of the regimen, the present analysis resolved to settle a long-standing debate concerning concurrent therapy vs a traditional sequential approach in which BR would be administered first, followed by acalabrutinib upon relapse. According to Dr Wang, many argued against switching to concurrent therapy, questioning whether using 3 drugs together was better than the sequential approach.

Accordingly, the 50-month analysis re-assessed the time to next treatment 2 (TTNT2) among 299 patients with MCL receiving either concurrent or sequential therapy, which measures the period from the initiation of therapy until the patient required third-line treatment.

Results showed that the TTNT2 period was much longer in the concurrent arm, suggesting that the concurrent regimen (acalabrutinib plus BR) achieved a better result than the sequential regimen. The longer follow-up also confirmed that the efficacy of the concurrent therapy still holds without toxicity significantly increasing. Dr Wang asserts that concurrent therapy yields superior results compared with sequential therapy and therefore believes should be used. He also believes that these findings, drawn from a randomized trial, serve as more robust evidence against previous retrospective reviews suggesting the 2 methods were equally effective.

REFERENCES

1. Wang M, Paludo J, de Holanda Farias JS, et al. Time to third-line treatment after bendamustine-rituximab with or without acalabrutinib in patients with previously untreated mantle cell lymphoma: Updated analysis of the phase 3 ECHO trial after 50 months of follow-up. Blood. 2025;146(Supplement 1):885-885. doi:10.1182/blood-2025-885