AZ’s Calquence extends disease-free survival in MCL
AstraZeneca’s Calquence has been shown to improve progression-free survival in previously untreated mantle cell lymphoma (MCL), with an unprecedented trend towards improved overall survival for the BTK inhibitor class in this cancer.
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 newly diagnosed MCL patients, according to data from the ECHO trial reported at the EHA congress in Madrid today.
Median PFS was 66.4 months for patients treated with Calquence versus 49.6 months with standard care, and the ECHO data also revealed a 14% improvement in OS. That was not a significant difference, but AZ said the data is not mature yet and patients will continue to be followed up.
It’s worth noting that ECHO generated a lot of data during the COVID-19 pandemic, and an analysis stripping out COVID-related deaths suggests an even greater improvement in PFS of around 36% and an (also not significant) 25% difference in OS.
Calquence is already approved in the US, China, and other countries for the treatment of adult patients with MCL who have received at least one prior therapy, as well as being used to treat patients with chronic lymphocytic leukaemia (CLL) and small lymphocytic leukaemia (SLL).
It is in the same class as AbbVie and Johnson & Johnson’s Imbruvica (ibrutinib), which is a major blockbuster, but had its indication in previously treated MCL withdrawn after it failed the confirmatory SHINE trial, improving PFS by 25% when added to BR, but showing a trend towards worse survival.
Imbruvica is still approved for CLL, Waldenström’s macroglobulinemia (WM), and chronic graft-versus-host disease (GVHD) and made $3.5 billion for AbbVie and $3.3 billion for J&J last year. It has, however, been gradually losing market share to Calquence, as well as BeiGene’s Brukinsa (zanubrutinib), which made sales of $2.5 billion and $1.3 billion, respectively, last year.
Brukinsa has been growing particularly quickly, thanks to broad labelling across previously treated MCL and various lines of therapy for CLL, WM, marginal zone lymphoma (MZL), and follicular lymphoma (FL), but both new-generation BTK inhibitors have benefitted from having a reduced risk of side effects compared to Imbruvica.
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, FL, and diffuse large B-cell lymphoma (DLBCL).
It remains to be seen whether AZ will be able to file for approval of Calquence in MCL, given the earlier experience with Imbruvica in this indication, and the company has previously said it will discuss the data with regulators.
AZ’s head of oncology R&D, Susan Galbraith, said that they "believe Calquence plus chemoimmunotherapy will be an important new option for patients living with this disease.”
