FDA Grants Priority Review to AstraZeneca’s Calquence for Previously Untreated Mantle Cell Lymphoma

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The FDA has granted Priority Review to AstraZeneca’s Calquence (acalabrutinib) for adult patients with previously untreated mantle cell lymphoma (MCL). According to the company, this regulatory decision was based on results from the Phase III ECHO clinical trial, which found that Calquence combined with bendamustine and rituximab significantly reduced the risk of disease progression or death compared to standard chemoimmunotherapy.¹

“Today’s Priority Review acceptance reinforces the potential of Calquence to transform outcomes in untreated mantle cell lymphoma. Data from the ECHO trial showed Calquence 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 this potential new treatment as soon as possible,” said Susan Galbraith, EVP, oncology R&D, AstraZeneca, in a press release.

The randomized, double-blind, placebo-controlled, multi-center ECHO trial evaluated the efficacy and safety of Calquence plus bendamustine and rituximab compared to standard-of-care chemoimmunotherapy in adults over 65 years of age with previously untreated MCL. During the trial, patients were randomly assigned in a 1:1 ratio to receive either Calquence or placebo administered orally twice per day, continuously, until disease progression or unacceptable toxicity. The primary endpoint of the study was progression-free survival (PFS) as assessed by an Independent Review Committee, with secondary endpoints that included overall survival (OS), overall response rate, duration of response, and time to response.

Results show that the combination therapy reduced the risk of disease progression or death by 27%, at close to 1.5 years of additional median PFS (mPFS), totaling an mPFS of 66.4 months compared with 49.6 months with standard-of-care. While OS was more promising in the Calquence group, the data wasn’t mature at the time of this analysis, according to the trial investigators.¹

The safety and tolerability of Calquence was consistent with its known profile. Adverse events (AEs) of Grade 3 or higher occurred in 88.9% of patents in the Calquence group and 88.2% of patients in the standard-of-care chemoimmunotherapy. This included AEs grade 3 or higher atrial fibrillation, hypertension, major bleeding, and infections. AEs resulting in treatment discontinuation occurred in 10.4% of patients administered the Calquence combination and 6.4% of patients in the standard-of-care arms.²

MCL accounts for 3% to 7% of non-Hodgkin lymphomas in the United States and Europe, with an incidence estimated to be four to eight cases per million people annually. The median diagnosis age is 68 years, three-quarters of all MCL patients are male, with White individuals being affected nearly twice as much as Black individuals.³

According to Medscape, nearly 70% of patients with MCL are diagnosed in stage IV. Additionally, it is typically diagnosed between 35 and 85 years of age.⁴

"For people living with mantle cell lymphoma, a typically aggressive form of non-Hodgkin's lymphoma, the ECHO results offer promise of a new, effective treatment option for adults older than 65, who represent the majority of MCL patients. The improved progression-free survival seen in patients treated with the Calquence combination compared to chemoimmunotherapy demonstrate its potential to change the standard of care as the only BTK inhibitor in this first-line setting,” said Michael Wang, MD, Puddin Clarke Endowed Professor, director, Mantle Cell Lymphoma Program of Excellence, co-director, clinical trials, MD Anderson Cancer Center, Houston, Texas, in a press release.²

Currently, a supplemental New Drug Application is under review as Project Orbis, an initiative started by the FDA that aims to provide a framework for concurrent submission and review of oncology medicines among participating international partners to bring cancer treatments to patients around the world as early as possible.¹

References

1. Calquence granted Priority Review in the US for patients with untreated mantle cell lymphoma. AstraZeneca. 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. Calquence plus chemoimmunotherapy reduced the risk of disease progression or death by 27% vs. standard of care in patients with untreated mantle cell lymphoma in ECHO Phase III trial. AstraZeneca. June 16, 2024. Accessed October 3, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/calquence-plus-chemoimmunotherapy-reduced-the-risk-of-disease-progression-or-death-by-27-percent.html

3. Mantle cell lymphoma: Epidemiology, pathobiology, clinical manifestations, diagnosis, and prognosis. UpToDate. Accessed October 3, 2024. https://www.uptodate.com/contents/mantle-cell-lymphoma-epidemiology-pathobiology-clinical-manifestations-diagnosis-and-prognosis#:~:text=Mantle%20cell%20lymphoma%20(MCL)%20accounts,at%20diagnosis%20is%2068%20years.

4. Mantle Cell Lymphoma. Medscape. June 7, 2024. Accessed October 3, 2024. https://emedicine.medscape.com/article/203085-overview