Acalabrutinib Combined With BR Improves Survival in Treatment-Naïve Mantle Cell Lymphoma

The phase 3 ECHO trial evaluated the efficacy and safety of adding the second-generation BTK inhibitor acalabrutinib to standard bendamustine-rituximab (BR) in patients with previously untreated mantle cell lymphoma (MCL). A total of 598 patients were randomized to receive either acalabrutinib + BR (A+BR) or placebo + BR (P+BR), followed by maintenance with acalabrutinib or placebo.

After a median follow-up of 61.6 months, the A+BR arm demonstrated a significant improvement in progression-free survival (PFS), with a median not reached versus 49.6 months in the control arm (HR, 0.61; 95% CI, 0.45–0.83; P=0.0012). The 5-year PFS rate was 64.1% in the A+BR group compared to 52.2% in the P+BR group.

The combination also yielded a higher rate of complete response (CR): 65.7% vs. 56.0%, and a greater proportion of patients achieved undetectable minimal residual disease (uMRD) in peripheral blood at cycle 6 (38.4% vs. 24.4%).

The safety profile of A+BR was consistent with known effects of each agent. Grade ≥3 adverse events were slightly more common in the A+BR group (84.6% vs. 77.4%), with neutropenia (56.1%), anemia (12.5%), and thrombocytopenia (11.5%) being the most frequent hematologic toxicities. Rates of atrial fibrillation and bleeding events remained low and comparable between groups.

These findings support A+BR as an effective front-line regimen for patients with MCL, offering a chemotherapy backbone augmented by targeted BTK inhibition and deeper remissions. This strategy may represent a new standard for younger or transplant-ineligible patients with newly diagnosed MCL.

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