FDA approves acalabrutinib with bendamustine and rituximab for previously untreated mantle cell lymphoma
Regulatory approval: On Jan 16, 2025, the FDA granted traditional approval for acalabrutinib (Calquence) with bendamustine and rituximab for adults with previously untreated mantle cell lymphoma who are ineligible for autologous HSCT. Approval was supported by the phase 3 ECHO trial (NCT02972840), showing longer PFS vs placebo plus BR (HR 0.73; p=0.016). The FDA also granted traditional approval to single-agent acalabrutinib for previously treated MCL, converting its 2017 accelerated approval.
FDA approval (Jan 16, 2025): acalabrutinib + bendamustine/rituximab in untreated MCL
The US FDA granted traditional approval to acalabrutinib (Calquence, AstraZeneca) plus bendamustine and rituximab (BR) for adults with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation (HSCT).
The FDA also granted traditional approval to acalabrutinib monotherapy for adults with previously treated MCL, converting the drug’s 2017 accelerated approval for this indication.
Supporting evidence (ECHO; NCT02972840)
Efficacy was evaluated in ECHO, a randomized, double-blind, placebo-controlled, multicenter trial enrolling 598 patients with untreated MCL who were ≥65 years and not intended to receive HSCT. Patients were randomized 1:1 to acalabrutinib + BR vs placebo + BR.
Primary efficacy endpoint was progression-free survival (PFS) by independent review committee. At median follow-up 49.8 months, PFS was statistically significantly longer with acalabrutinib + BR (HR 0.73, 95% CI 0.57–0.94; p=0.016). Median PFS was 66.4 months (95% CI 55.1–NE) vs 49.6 months (95% CI 36.0–64.1).
Safety and dosing (as reported)
With acalabrutinib + BR, serious adverse reactions occurred in 69% and fatal adverse reactions in 12%. The recommended acalabrutinib dose is 100 mg orally approximately every 12 hours until progression or unacceptable toxicity.
This review was conducted under Project Orbis; reviews at partner agencies were ongoing at the time of the FDA action.