Acalabrutinib Combo Improves PFS Over Standard of Care in Mantle Cell Lymphoma

Image of lymphoma cells: © David A Litman - www.stock.adobe.com.jpg

The combination of acalabrutinib (Calquence) plus bendamustine and rituximab (Rituxan) delivered a statistically significant improvement in progression-free survival (PFS) over the standard of care in patients with previously untreated mantle cell lymphoma (MCL), according to an interim analysis of the phase 3 ECHO trial (NCT02972840).¹

Safety reports are consistent with acalabrutinib’s known profile, and no new signals were identified.

The data will be presented at an upcoming medical meeting and shared with regulatory authorities.

“These positive progression-free survival results from the ECHO phase 3 trial could provide a new standard of care for patients with mantle cell lymphoma. Incorporating [acalabrutinib] into the first-line mantle cell lymphoma setting would give many more patients the opportunity to benefit from the robust efficacy and strong safety profile we’ve seen with this medicine,” said Michael Wang, MD, Puddin Clarke Endowed Professor, director of Mantle Cell Lymphoma Program of Excellence, codirector of clinical trials at MD Anderson Cancer Center, and principal investigator of the trial, said in a press release.

Acalabrutinib is currently approved for the treatment of patients with chronic lymphocytic leukemia and small lymphocytic lymphoma in the US, as well as for patients with MCL who have received at least 1 prior line of therapy. Acalabrutinib is also being investigated for the treatment of other B-cell blood cancers, including diffuse large B-cell lymphoma.

“These impactful results in mantle cell lymphoma show that bringing [acalabrutinib] to the first-line setting significantly delays disease progression and, for the first time, shows potential to extend survival. The improvement in progression-free survival together with the differentiated safety profile of [acalabrutinib] are both important as we strive to transform outcomes earlier in the course of disease treatment,” said Susan Galbraith, executive vice president of oncology research and development, AstraZeneca, said in the press release.

About the Phase 3 ECHO Trial

ECHO is a phase 3, randomized, double-blind-placebo controlled, multicenter study investigating bendamustine plus rituximab alone as well as in combination with acalabrutinib in patients with previously untreated MCL. A total of 635 patients are enrolled across sites in 18 states and Washington, D.C., as well as 26 other countries.²

The study’s primary end point is PFS, and secondary end points include overall response rate, overall survival, duration of response, and time to response. Patients were randomized to receive acalabrutinib or a placebo administered orally twice daily plus bendamustine on days 1 and 2 and rituximab on day 1 for a 28-day cycle.

Patients 65 or younger with pathologically confirmed MCL, an ECOG performance status of 2 or less, and documentation of a chromosome translocation or relevant overexpression were eligible for enrollment. Those with significant cardiovascular disease, malabsorption syndrome, or uncontrolled infections were not eligible for participation in the study.

The study has an estimated completion date of October 28, 2024.

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 2, 2024. https://tinyurl.com/mv5ukjud

2. A study of BR alone versus in combination with acalabrutinib in subjects with previously untreated MCL. ClinicalTrials.gov. Updated March 8, 2024. Accessed May 2, 2024. https://clinicaltrials.gov/study/NCT02972840