Acalabrutinib Combo Yields PFS Improvement Vs SOC in Mantle Cell Lymphoma

“These positive [PFS] results from the phase 3 ECHO trial could provide a new standard of care for patients with [MCL],” according to Michael Wang, MD.

Combining acalabrutinib (Calquence) with bendamustine and rituximab (Rituxan) elicited a clinically meaningful and statistically significant progression-free survival (PFS) improvement over standard of care in adult patients with previously untreated mantle cell lymphoma (MCL), according to a press release on findings from the phase 3 ECHO trial (NCT02972840).¹

Investigators also noted a favorable overall survival (OS) trend with the acalabrutinib-based combination, although these data were immature at the time of the analysis. The trial will continue with its evaluation of this end point.

The safety and tolerability of acalabrutinib in the ECHO trial were comparable with prior reports of the agent, and investigators observed no new safety signals.

Developers plan to present data at a future medical meeting and share their findings with regulatory health authorities globally.

“These positive [PFS] results from the phase 3 ECHO trial could provide a new standard of care for patients with [MCL],” principal investigator Michael Wang, MD, Puddin Clarke Endowed professor, director of Mantle Cell Lymphoma Program of Excellence, and co-director of Clinical Trials at The University of Texas MD Anderson Cancer Center, said in the press release.¹ “Incorporating [acalabrutinib] into the first-line [MCL] setting would give many more patients the opportunity to benefit from the robust efficacy and strong safety profile we’ve seen with this medicine.”

In the double-blind, multi-center phase 3 ECHO trial, 598 patients with previously untreated MCL who were 65 years or older were randomly assigned to receive acalabrutinib or matched placebo orally twice a day as part of a 28-day regimen. Additionally, patients received bendamustine on days 1 and 2 plus rituximab on day 1. After 6 cycles of treatment, patients received acalabrutinib or placebo plus maintenance with rituximab for 2 years followed by acalabrutinib or placebo only until progressive disease.

Investigators assessed patients across 27 countries within North America, South America, Europe, Asia, and Oceania. The trial took place from 2017 to 2023 throughout the COVID-19 pandemic.

The trial’s primary end point was PFS. Secondary end points included OS, overall response rate, duration of response, and time to response.

Patients 65 years and older with pathologically confirmed MCL and no documentation of a chromosome translocation and/or overexpression of cyclin D1 related to other relevant markers such as CD5, CD19, and CD20 were eligible for enrollment on the trial.² Additional eligibility criteria included having disease requiring management for which no prior systemic anticancer therapies had been used and an ECOG performance status of 0 to 2.

Those with significant cardiovascular disease including uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of beginning study treatment or any Class 3 or 4 cardiac disease based on New York Heart Association Functional Classification were unable to enroll on the trial. Patients were also unsuitable for enrollment if they had malabsorption syndrome, significant gastrointestinal disease, stomach resection, or symptomatic inflammatory bowel disease. Having uncontrolled active systemic fungal, bacterial, or viral infections or receipt of intravenous anti-infective agents within 2 weeks of beginning study treatment was also grounds for exclusion from the trial.

“These impactful results in [MCL] show that bringing [acalabrutinib] to the first-line setting significantly delays disease progression and, for the first time, shows potential to extend survival,” Susan Galbraith, executive vice president of Oncology Research and Development at AstraZeneca, said.¹ “The improvement in [PFS] together with the differentiated safety profile of [acalabrutinib] are both important as we strive to transform outcomes earlier in the course of disease treatment.”

References

1. Calquence combination regimen demonstrated statistically significant and clinically meaningful improvement in progression-free survival in 1st-line mantle cell lymphoma in ECHO phase III trial. News release. AstraZeneca. May 2, 2024. Accessed May 3, 2024. https://tinyurl.com/py9tdkp6
2. A study of BR alone versus in combination with acalabrutinib in subjects with previously untreated MCL. ClinicalTrials.gov. Accessed May 3, 2024. https://tinyurl.com/2wfcah46