Dr Victoria Otero (AstraZeneca, MD, USA) presented on behalf of the first author, Prof. Martin Dreyling (Medizinische Klinik III, Klinikum der Universität München, Germany), at the 13th Society of Hematologic Oncology (SOHO) 2025 Annual Meeting in Houston, TX [1].
The ECHO study randomised patients aged 65 years or older with untreated MCL to receive ABR or placebo plus BR (PBR). BR was given for 6 cycles, followed by rituximab maintenance in patients achieving a partial or complete response. Acalabrutinib (100 mg twice daily) or placebo was continued until progression or unacceptable toxicity, and crossover to acalabrutinib was allowed at progression. High-risk disease was defined by high-risk MIPI (6–11), TP53 mutation, Ki-67 index of 30% or higher, or blastoid/pleomorphic histology.
As of February 2024, 299 patients were assigned to each treatment arm. High-risk disease was present in 62.5% of the ABR arm (n=187) and 61.2% in the PBR arm (n=183). In this subgroup, 24% had high-risk MIPI, 7-10 percent carried TP53 mutations, nearly half had a Ki-67 index of at least 30%, and 13% had blastoid or pleomorphic histology.
Among high-risk patients, the complete response rate and overall response rate were 67.9% and 89.8%, respectively, in the ABR arm compared with 47.5% and 84.7% with PBR. Median progression-free survival was significantly longer with ABR at 49.5 months compared with 36.0 months for PBR (HR 0.74; 95% CI 0.55–0.99; P=0.0432). After progression, 38 patients in the placebo arm crossed over to acalabrutinib. The hazard ratio for overall survival with ABR versus PBR was 0.87 (95% CI 0.64–1.19; P=0.3913). When deaths attributed to COVID-19 were censored, the hazard ratio was 0.76 (95% CI 0.53–1.10; P=0.1459).
These findings confirm that adding acalabrutinib to BR results in deeper responses and a significant progression-free survival advantage in high-risk MCL, although overall survival differences have not yet reached statistical significance. This reflects the challenge of demonstrating survival benefit in trials with crossover and competing risks such as COVID-19. The ECHO analysis provides reassurance that BTK inhibition combined with chemoimmunotherapy can achieve more durable remissions in this difficult population.
- Otero V, et al. Efficacy of Rituximab-Bendamustine With or Without Acalabrutinib in Patients With Untreated, High-Risk Mantle Cell Lymphoma: An Analysis of the Phase 3 ECHO Trial. Abstract MCL-725, SOHO 2025, 2-7 September 2025.
Medical writing support was provided by Dr Rachel Giles.
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