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ECHO: Can we expect a novel standard of care in newly diagnosed MCL?

Presented by
Prof. Michael Wang, University of Texas, TX, USA
Conference
EHA 2024
Trial
Phase 3, ECHO
Doi
https://doi.org/10.55788/5470b753
A first-line treatment regimen of acalabrutinib added to bendamustine and rituximab (BR) decreased the risk of disease progression or death compared with a regimen of BR and a placebo in older participants with mantle cell lymphoma (MCL) in the phase 3 ECHO trial.

“Although intensive frontline therapies can deliver durable responses in patients with MCL, these treatments are not suited for older patients due to poor tolerability,” elaborated Prof. Michael Wang (University of Texas, TX, USA) [1]. Thus, BR is therefore the most frequently administered first-line therapy in this population. Recently, the addition of the BTK inhibitor acalabrutinib to BR delivered promising safety and efficacy results in a phase 1 study (NCT02717624) [2].

To further evaluate this combination therapy, the current phase 3 ECHO trial (NCT02972840) randomised 598 participants over 64 years of age with newly diagnosed MCL 1:1 to BR plus acalabrutinib or BR plus placebo. The primary endpoint was progression-free survival (PFS). “Participants in the placebo arm were permitted to cross over to acalabrutinib if they had disease progression,” noted Prof. Wang.

After a median follow-up of 45 months, PFS was improved in the acalabrutinib arm compared with the placebo arm (HR 0.73; 95% CI 0.57–0.94; P=0.016). The median PFS was 66.4 months in the acalabrutinib and 49.6 months in the placebo arm. Of note, 69% of the participants in the placebo arm received BTK inhibitors as a subsequent treatment. According to Prof. Wang, there was also a positive trend in OS, with a hazard ratio of 0.86 (95% CI 0.65–1.13; P=0.27). “If we censor for COVID-related deaths the OS trend was even more positive,” emphasised Prof. Wang (HR 0.75; 95% CI 1.04; P=0.08; see Figure).

Figure: A pre-specified sensitivity analysis of OS with and without COVID-19 deaths [1]



ABR, acalabrutinib plus bendamustine and rituximab; NE, not estimable; OS, overall survival; PBR, placebo plus bendamustine and rituximab.

The safety profiles of the 2 treatment regimens did not differ substantially. Atrial fibrillation occurred in 6.1% of the participants on acalabrutinib and in 4.4% of placebo. Hypertension (12.1% vs 15.8%) and major bleeding (2.4% vs 5.4%) were slightly more common in the placebo arm, whereas infections (78.1% vs 71.0%) were more frequently reported in the acalabrutinib arm.

“The data from ECHO indicate that acalabrutinib plus BR may be a new first-line standard of care for older patients with MCL,” concluded Prof. Wang.

  1. Wang M, et al. Acalabrutinib plus bendamustine and rituximab in untreated mantle cell lymphoma: results from the phase 3, double-blind, placebo-controlled ECHO trial. LB3439, EHA congress 2024, 13–16 June, Madrid, Spain.
  2. Phillips TJ, et al. J Clin Oncol. 2023;41(16 suppl):7546.

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