First-Line Treatment with Calquence Plus Chemoimmunotherapy Found to Improve Survival in Patients with Mantle Cell Lymphoma

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Calquence (acalabrutinib; AstraZeneca) plus standard-of-care chemoimmunotherapy produced a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in adults who have not received prior treatment for mantle cell lymphoma (MCL), according to an interim analysis of findings from the Phase III ECHO trial.¹ Calquence, a next-generation Bruton’s tyrosine kinase (BTK) inhibitor, was approved by the FDA in October 2017 to treat patients with MCL previously administered at least one prior therapy.² In November 2019, the BTK inhibitor was also approved for adults with chronic lymphocytic leukemia and small lymphocytic lymphoma.³

“These positive progression-free survival results from the ECHO Phase III trial could provide a new standard of care for patients with mantle cell lymphoma,” principal trial investigator Michael Wang, MD, Puddin Clarke Endowed Professor, director of Mantle Cell Lymphoma Program of Excellence, co-director of Clinical Trials at MD Anderson Cancer Center, said in a press release. “Incorporating Calquence 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.”¹

MCL, a rare and aggressive form of non-Hodgkin lymphoma, is frequently diagnosed in the later stages after B-lymphocytes mutate into malignant cells in the mantle zone region of the lymph node. Over 27,500 patients have been diagnosed with MCL worldwide.¹

The randomized, double-blind, placebo-controlled, multi-center ECHO trial compared the efficacy and safety of Calquence combined with standard-of-care chemoimmunotherapy comprised of bendamustine and rituximab vs. placebo with bendamustine and rituximab in adults aged 65 years or older (n=598) with previously untreated MCL.

Patients were randomly assigned at a 1:1 ratio to receive either Calquence or placebo, administered orally twice daily over a 28-day treatment cycle, plus bendamustine on days one and two and rituximab on day one. Following six cycles of Calquence or placebo plus bendamustine and rituximab, patients were administered Calquence or placebo combined with maintenance rituximab for two years and then either Calquence or placebo until disease progression.

The trial’s primary endpoint is PFS with key secondary endpoints that include overall survival (OS), overall response rate, duration of response, and time to response. The ECHO trial was conducted from 2017 to 2023 in 27 countries throughout North America, South America, Europe, Asia, and Oceania. In addition to the clinically meaningful benefit demonstrated in PFS, the investigators observed a trend in favor of the Calquence combination for the secondary endpoint of OS. The OS data were immature at the time of the interim analysis, with the trial ongoing to assess this endpoint.

In terms of safety, the profile of Calquence was consistent with prior findings, with no new safety signals identified. The most common adverse events associated with Calquence are headache, diarrhea, musculoskeletal pain, upper respiratory tract infection, and bruising.⁴

Data from the interim analysis will be presented at an upcoming medical meeting and submitted to global regulatory authorities, according to AstraZeneca.

“These impactful results in mantle cell lymphoma show that bringing Calquence to the first-line setting significantly delays disease progression and, for the first time, shows potential to extend survival,” Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, said in a press release. “The improvement in progression-free survival together with the differentiated safety profile of Calquence are both important as we strive to transform outcomes earlier in the course of disease treatment.”¹

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. FDA approves new treatment for adults with mantle cell lymphoma. News release. FDA. October 31, 2017. Accessed May 2, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-adults-mantle-cell-lymphoma

3. Calquence approved in the US for adult patients with chronic lymphocytic leukaemia. News release. AstraZeneca. November 21, 2019. Accessed May 2, 2024. https://www.astrazeneca.com/media-centre/press-releases/2019/calquence-approved-in-the-us-for-adult-patients-with-chronic-lymphocytic-leukaemia-21112019.html#

4. Calquence. Prescribing information. AstraZeneca Pharmaceuticals LP; 2019. Accessed May 2, 2024. https://www.azpicentral.com/calquence/calquence.pdf