Acalabrutinib Plus Bendamustine and Rituximab Approved for Previously Untreated Mantle Cell Lymphoma
Expert Perspectives · Lyn Brook · 2025-01-20
The FDA has approved acalabrutinib (Calquence®, AstraZeneca) with bendamustine and rituximab (BR) for adults with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation (HSCT).
In addition, the FDA approved acalabrutinib as a single agent for adults with previously treated MCL. This indication was previously granted accelerated approval in 2017.
Why Is the Approval of Acalabrutinib Important?
“Aggressive first-line therapies for MCL can provide durable responses and prolonged progression-free survival but are unsuitable for elderly or unfit patients due to poor tolerability,” said Michael Wang, MD, Professor of Lymphoma and Myeloma at MD Anderson Cancer Center, and colleagues, in their abstract presented at the European Hematology Association, regarding the ECHO (NCT02972840) trial. “The addition of the Bruton tyrosine kinase inhibitor ibrutinib to chemoimmunotherapy (BR) for first-line treatment of MCL has been shown to prolong progression-free survival, but with detrimental overall survival due to excess toxicity.”
Investigating Acalabrutinib in ECHO
Efficacy was studied in the phase 3, double-blind, placebo-controlled, multicenter trial which enrolled 598 patients with untreated MCL who were ≥65 years of age and not intended to receive HSCT. Patients were randomized 1:1 to receive either acalabrutinib plus BR or placebo plus BR. The primary end point measured was progression-free survival, as assessed by an independent review committee.
Progression-free survival saw a statistically significant improvement in the acalabrutinib arm. The median progression-free survival in the acalabrutinib arm was 66.4 months compared with the placebo arm which saw a median of 49.6 months. The median follow-up was 49.8 months.
Adverse Events
Serious adverse reactions reported in ≥2% of patients receiving acalabrutinib plus BR were pneumonia, COVID-19, pyrexia, second primary malignancy, rash, febrile neutropenia, atrial fibrillation, sepsis, and anemia. Serious adverse reactions were observed in 69% of patients treated with acalabrutinib and BR, with fatal reactions occurring in 12%.
Putting It Into Context
“Acalabrutinib in combination with BR provides a significant progression-free survival benefit in patients with previously untreated MCL, including those with high-risk features,” wrote Martin Dreyling, MD, and colleagues, in their updated results from the ECHO trial, presented at American Society of Hematology Annual Meeting. “Furthermore, the addition of acalabrutinib to BR provided a greater progression-free survival effect among patients in the acalabrutinib plus BR arm with the longest exposure to acalabrutinib.”
Dosing Instructions
The recommended dosage of acalabrutinib is 100 mg taken orally approximately every 12 hours until disease progression or unacceptable toxicity.