Acalabrutinib + bendamustine + rituximab in high-risk MCL: A subgroup analysis of the phase III ECHO trial

Results from the randomized, double-blind, placebo-controlled, phase III ECHO trial (NCT02972840) showed that acalabrutinib + bendamustine + rituximab (ABR) improved progression-free survival vs placebo + bendamustine + rituximab (PBR) in patients with previously untreated mantle cell lymphoma (MCL).¹ Generally, patients with high-risk features, such as a Ki-67 index ≥30%, high-risk MCL International Prognostic Index (MIPI), blastoid/pleomorphic histology, or TP53 mutations respond poorly to standard therapy.¹ 

During the European Hematology Association (EHA) 2025 Congress, June 12–15, 2025, Milan, IT, Martin Dreyling presented efficacy outcomes from a subgroup analysis of the ECHO trial in patients with high-risk MCL (N = 370).¹

Key learnings

The ORR was 89.8% in the ABR arm and 84.7% in the PBR arm (p = 0.1382). The ABR arm showed a higher CR rate compared with the PBR arm (67.9% vs 47.5%; p < 0.0001). 

The median PFS was longer in the ABR vs PBR arm (49.5 months vs 36.0 months; HR, 0.74; 95% CI, 0.55–0.99; p = 0.0432), while the median OS was NE vs 68.0 months (HR, 0.87; 95% CI, 0.64–1.19; p = 0.3913). 

In the ABR vs PBR arms, the median PFS was 49.5 months vs 33.2 months (HR, 0.66; 95% CI, 0.48–0.91; p = 0.0119) in patients with biologically high-risk features (Ki-67 index ≥30%, high-risk MIPI, blastoid/pleomorphic histology, or TP53 mutations).  

ABR vs PBR showed a PFS benefit in patients with blastoid/pleomorphic histology (HR, 0.59; 95% CI, 0.33–1.07; p = 0.0775) and Ki-67 index ≥30% (HR, 0.63; 95% CI, 0.45–0.89; p = 0.0084) compared with the total study population (HR 0.73).

The findings were consistent with the primary analysis of the ECHO trial, with longer PFS and higher CR rates in patients with high-risk MCL treated with ABR vs PBR.