FDA Approves First BTK Inhibitor as First-Line Therapy for Mantle Cell Lymphoma

British biopharmaceutical company AstraZeneca recently announced the FDA approval of Bruton tyrosine kinase (BTK) inhibitor Calquence (acalabrutinib) for the first-line treatment of mantle cell lymphoma (MCL).

For this indication, Calquence is approved for use in combination with bendamustine chemotherapy and rituximab immunotherapy in adults with no previous MCL treatment and who are ineligible for stem cell transplantation.

The drug received accelerated approval in October 2017 as monotherapy for adults with MCL who have received at least one prior treatment. The FDA simultaneously converted the conditional approval to full approval for this indication.

MCL is a rare and typically aggressive form of non-Hodgkin lymphoma, representing about 6% of all new non-Hodgkin lymphoma cases in the United States. Patients with MCL typically respond to available treatments, but remission periods are usually short.

Calquence’s approval as a first-line treatment was based on results from the pivotal phase 3 ECHO trial, which included adults ages 65 years and older with previously untreated MCL. The participants were randomized to receive Calquence plus the standard-of-care chemoimmunotherapy (bendamustine and rituximab) or placebo plus the standard-of-care.

The trial results showed that Calquence plus bendamustine and rituximab lowered the risk of disease progression or death by 27% versus standard-of-care. Mean progression-free survival was 66.4 months for patients who received the Calquence treatment combination compared with 49.6 months for those receiving only chemoimmunotherapy.

“New treatment options have long been needed in the first-line treatment of mantle cell lymphoma in the U.S.,” Meghan Gutierrez, chief executive officer of the Lymphoma Research Foundation, said in a media release.

“Patients with this rare and often aggressive cancer can experience severe symptoms by the time they are diagnosed - having an effective therapy that can significantly improve outcomes for patients early in the treatment process is a much-needed advancement,” she added.

The FDA reviewed Calquence plus chemoimmunotherapy under Project Orbis, which allows for concurrent submissions and review of oncology treatments within participating countries. The treatment is also under regulatory review in Australia, Canada, and Switzerland as part of Project Orbis.

In November 2019, the FDA approved Calquence as monotherapy for the treatment of chronic lymphocytic leukemia and small lymphocytic lymphoma in adults.