AstraZeneca Supports Calquence's Promise in Mantle Cell Lymphoma with Detailed Data

In a recent development, AstraZeneca announced significant findings from their ECHO study, which examined the efficacy of their blood cancer drug Calquence when combined with standard-of-care chemotherapy for treating mantle cell lymphoma (MCL). The study revealed that adding Calquence to a regimen of bendamustine and rituximab (BR) reduced the risk of disease progression or death by 27%. This figure is both statistically significant and clinically meaningful, as presented at the European Hematology Association (EHA) Congress in Madrid.

The phase 3 trial involved 299 patients aged 65 and older in each treatment arm. Data showed that the combination of Calquence and BR achieved a median progression-free survival (PFS) of 66.4 months, compared to 49.6 months for BR alone. Notably, Calquence also demonstrated a favorable trend in overall survival (OS), a first for a BTK inhibitor. However, AstraZeneca emphasized that the OS data is still maturing and will continue to be monitored as a secondary endpoint in the ongoing trial.

Benjamin Moutier, AstraZeneca’s global franchise head of hematology, highlighted the positive trend in OS as reassuring, even if it is not yet statistically significant. Both PFS and OS improvements were more marked when the analysis accounted for COVID-related deaths, given that the trial has been ongoing since 2017.

The study also showed promising complete remission rates of 67% in the Calquence arm compared to 53.5% in the BR arm. While overall response rates were similar, at 91% and 88% respectively, the addition of Calquence did not significantly increase the rate of adverse events between the two treatment arms. Moutier noted that the addition of Calquence to the existing BR regimen did not result in much more toxicity but significantly improved efficacy. He suggested that for physicians treating MCL patients, the decision to add Calquence is straightforward and beneficial.

The trial's results also offered valuable insights for patients who had previously received BTK inhibitors. Moutier mentioned that more than two-thirds of patients in the control arm had received a BTK inhibitor in the second line, providing crucial "crossover" comparisons. The data suggested that treating patients immediately with a BTK inhibitor like Calquence is more advantageous than reserving its use for relapsed cases.

Calquence's success contrasts with the performance of other BTK inhibitors in MCL treatment. For instance, AbbVie and Johnson & Johnson's Imbruvica failed to demonstrate an overall survival benefit in a phase 3 trial last year, leading to the withdrawal of its accelerated approval for MCL. Although Imbruvica had shown a 25% reduction in the risk of disease progression or death, it didn’t meet the OS endpoint. BeiGene’s Brukinsa, another BTK inhibitor, received accelerated approval for previously treated MCL patients and is currently undergoing a phase 3 trial for first-line use, set to complete in 2027.

The market dynamics for MCL treatments are also shifting. While Imbruvica, approved for MCL in 2013, saw a decline in global sales by 21% to $3.6 billion last year, Calquence’s sales rose by 22% to $2.5 billion. Meanwhile, Brukinsa saw a remarkable 129% sales increase to $1.3 billion in 2023.

MCL is a rare and aggressive form of non-Hodgkin lymphoma (NHL), often diagnosed at an advanced stage. While initial responses to treatment are typically positive, relapse rates remain high. Approximately 4,000 new MCL cases are diagnosed annually, with about 27,500 people currently living with the disease.