Frontline Acalabrutinib Plus Chemoimmunotherapy Elicits Meaningful Survival Benefit in MCL

Acalabrutinib (Calquence) plus standard-of-care chemoimmunotherapy with bendamustine (Bendeka) and rituximab (Rituxan) led to a progression-free survival (PFS) benefit vs standard of care alone in adult patients with treatment-naive mantle cell lymphoma (MCL), according to findings from an interim analysis of the phase 3 ECHO trial (NCT02972840).¹

High-level data, which will be presented at an upcoming medical meeting and shared with regulatory agencies, demonstrated a statistically significant and clinically meaningful improvement in PFS with the addition of acalabrutinib to bendamustine and rituximab therapy. Additionally, patients treated on the investigational arm experienced a positive trend in terms of overall survival (OS) compared with standard of care treatment alone, although OS findings were not mature at the time of the analysis. Safety results were consistent with the known safety profile of acalabrutinib, with no new safety signals being reported.

“These positive PFS results from the phase 3 ECHO trial could provide a new standard of care for patients with MCL,” lead investigator, Michael Wang, MD, Puddin Clarke Endowed Professor, director of Mantle Cell Lymphoma Program of Excellence, and the co-director of clinical trials at The University of Texas MD Anderson Cancer Center in Houston, said in a press release. “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.”

ECHO is an ongoing double-blind, placebo-controlled, multicenter study that is enrolling adult patients who are at least 65 years of age with previously untreated MCL (n = 598). Eligible patients needed to have pathologically confirmed MCL with chromosome translocation t(11;14)(q13;q32) and/or overexpression of cyclin D1, an ECOG performance status of 2 or less, and agree to use effective forms of contraception during the course of the study, for 6 months following the last dose of bendamustine, and/or for 12 months following the last dose of rituximab.^1,2

Subsequent to enrollment, patients were randomly assigned 1:1 to receive oral acalabrutinib or placebo twice daily in 28-day treatment cycles. Both arms also received bendamustine on days 1 and 2 and rituximab on day 1 of each cycle. Following 6 cycles of acalabrutinib or placebo, patients were treated with acalabrutinib or placebo with maintenance rituximab for 2 years and then acalabrutinib or placebo monotherapy until disease progression.

The primary end point of the study was PFS per Lugano Classification for non-Hodgkin lymphoma. Secondary end points included overall response rate, OS, duration of response, and time to response.

Acalabrutinib was granted accelerated approval from the FDA in October 2017 for the treatment of adult patients with MCL following at least 1 prior line of therapy.3 The agent was also approved by the FDA for the treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in November 2019.4 Acalabrutinib has been approved for the treatment of CLL in the European Union (EU) and for relapsed/refractory CLL and SLL in China and Japan; the agent is not currently approved for MCL in Japan or the EU.¹

“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,” Susan Galbraith, PhD, executive vice president of Oncology R&D at AstraZeneca, said in the press release.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 2, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/calquence-combination-improved-pfs-in-1l-mcl.html
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://classic.clinicaltrials.gov/ct2/show/NCT02972840
3. FDA grants accelerated approval to acalabrutinib for mantle cell lymphoma. FDA. October 31, 2017. Accessed May 2, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-acalabrutinib-mantle-cell-lymphoma
4. FDA takes second action under international collaboration, approves new treatment option for patients with chronic lymphocytic leukemia. FDA. November 21, 2019. Accessed May 2, 2024. https://www.fda.gov/news-events/press-announcements/fda-takes-second-action-under-international-collaboration-approves-new-treatment-option-patients