AZ's Calquence gets first-line OK in mantle cell lymphoma

AstraZeneca's BTK inhibitor Calquence has become the first drug in the class to be approved by the US FDA as a treatment for adult patients with previously untreated mantle cell lymphoma (MCL) who are ineligible for stem cell transplantation.

The approval – which follows a priority review – is based on the results of the ECHO trial, which showed that Calquence (acalabrutinib), given in combination with bendamustine and rituximab (BR), reduced the risk of cancer progression or death by 27% compared with the standard chemoimmunotherapy in this group of MCL patients.

According to data reported at last year's European Haematology Association (EHA) congress, median progression-free survival (PFS) was 66.4 months for patients treated with Calquence versus 49.6 months with standard care, which was accompanied by a 14% trend towards improved overall survival.

Calquence – which is a competitor to AbbVie and Johnson & Johnson’s blockbuster Imbruvica (ibrutinib) – is already approved in the US to treat MCL patients who have received at least one prior therapy, as well as for chronic lymphocytic leukaemia (CLL) or small lymphocytic leukaemia (SLL).

AZ's drug has been steadily capturing market share from its rival after Imbruvica failed a confirmatory trial as a second-line treatment for MCL, causing an earlier approval to be withdrawn, along with BeiGene's rival BTK drug Brukinsa (zanubrutinib), which is also growing quickly.

The new first-line MCL indication gives Calquence a slice of the market of its own and could spur further growth of the drug, which grew 27% to $2.3 billion in the first nine months of 2024 and is AZ's third-largest cancer product. In the same period, Imbruvica fell around 7% to $2.5 billion, while Brukinsa more than doubled to $1.8 billion.

"New treatment options have long been needed in the first-line treatment of [MCL] in the US," commented Meghan Gutierrez, chief executive of the Lymphoma Research Foundation.

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

The new indication is also under review in Australia, Canada, and Switzerland, with applications pending in the EU, Japan, and other regions.

Meanwhile, Calquence is also being evaluated as a single treatment and in combination with standard-of-care chemoimmunotherapy for patients with multiple B-cell blood cancer indications, including CLL, MCL, follicular lymphoma, and diffuse large B-cell lymphoma (DLBCL).

Image by Gabriel Caponetti via Wikipedia. Own work, CC BY-SA 3.0