Acalabrutinib Gets Priority Review for Frontline MCL Treatment

The FDA will speed up its review of acalabrutinib for frontline mantle cell lymphoma.

The FDA granted a priority review to a supplemental new drug application for acalabrutinib (Calquence) for the frontline treatment of adults with mantle cell lymphoma (MCL), according to a press release from AstraZeneca, the manufacturer of the BTK inhibitor.¹

The Prescription Drug User Fee Act date is set for the first quarter of 2025.

The FDA based its decision on findings from the phase 3 ECHO trial² (NCT02972840) that were presented at the 2024 European Hematology Association (EHA) Congress in Brazil. Data showed that acalabrutinib plus standard-of-care chemoimmunotherapy, consisting of bendamustine and rituximab (Rituxan), led to a 27% reduction in the risk of disease progression or death compared with placebo plus chemoimmunotherapy (HR, 0.73; 95% CI, 0.57-0.94; P = .016).

Since the ECHO trial was conducted during the COVID-19 pandemic, the researchers also censored for COVID-19-related deaths. After doing so, the progression-free survival (PFS) benefit from acalabrutinib was even more pronounced, with a 36% reduction in the risk of disease progression or death (HR, 0.64; 95% CI, 0.48-0.84; P = .0017).

Additionally, adding acalabrutinib to the standard of care improved median PFS: 66.4 months in the acalabrutinib-containing group, compared to 49.6 months in the placebo-containing group.

“Data from the ECHO trial showed [acalabrutinib] plus chemoimmunotherapy significantly delayed disease progression and showed a trend to improved survival in patients with this currently incurable blood cancer. We are working closely with the FDA to provide patients with this potential new treatment as soon as possible,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said in the press release.

Overall survival (OS) data were not yet mature at the time of data collection. While there was not a statistically significant improvement in OS, the researchers on the ECHO trial did observe a favorable trend in the acalabrutinib group (HR, 0.86; 95% CI, 0.65-1.13; P = .2743), which was sustained over time. Of note, most patients in the standard-of-care arm who needed subsequent therapy went on to receive a BTK inhibitor, most commonly acalabrutinib, according to the release.

OS will continue to be assessed, according to AstraZeneca.

The most common adverse events (AEs) that occurred in 20% or more of patients with relapsed or refractory MCL were: anemia, thrombocytopenia, headache, neutropenia, diarrhea, fatigue, myalgia, and bruising. The most common non-hematologic AE that was grade 3 or higher was diarrhea, which occurred in 3.2% of patients.

References

1. Calquence granted priority review in the US for patients with untreated mantle cell lymphoma. News release. AstraZeneca. Published: October 3, 2024. Accessed October 3, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/calquence-granted-priority-review-in-the-us-for-patients-with-untreated-mantle-cell-lymphoma.html
2. Wang ML, Mayer J, Belada D, et al. Acalabrutinib plus bendamustine and rituximab in untreated mantle cell lymphoma: results from the phase 3, double-blind, placebo-controlled ECHO trial. Presented at: 2024 European Hematology Association Congress; June 13-16, 2024; Madrid, Spain. Abstract LBA3439.