Acalabrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has been approved by the US Food and Drug Administration (FDA) in combination with bendamustine and rituximab for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation.
The approval was granted by the FDA after the therapy secured Priority Review. It was based on results from the ECHO phase 3 trial, which were presented at the European Hematology Association 2024 Hybrid Congress.
This approval additionally converts acalabrutinib’s accelerated approval to a full approval for adult patients with MCL treated with at least one prior therapy, as granted by the FDA in October 2017.
Results from the ECHO trial showed acalabrutinib plus bendamustine and rituximab reduced the risk of disease progression or death by 27% compared to standard-of-care chemoimmunotherapy (HR, 0.73; 95% CI, 0.57-0.94; P=0.016). Median progression-free survival (PFS) was 66.4 months for patients treated with the acalabrutinib combination versus 49.6 months with chemoimmunotherapy alone.
The ECHO trial enrolled patients throughout the COVID-19 pandemic. After censoring for COVID-19 deaths, the PFS was further improved in both arms, with the acalabrutinib combination reducing the risk of disease progression or death by 36% (HR 0.64; 95% CI, 0.48-0.84). Although overall survival (OS) data were not mature at the time of the analysis, when censored for COVID-19, a favorable trend was seen for OS (HR 0.75; 95% CI 0.53-1.04), despite 69% of patients in the chemoimmunotherapy arm receiving treatment with a BTK inhibitor on relapse or disease progression.
The safety and tolerability of acalabrutinib was consistent with its known safety profile, and no new safety signals were identified.
Besides MCL, acalabrutinib is also indicated as monotherapy for the treatment of adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.
