Calquence Plus Venetoclax Approved as First All-Oral Treatment for CLL
The U.S. Food and Drug Administration (FDA) has approved AstraZeneca’s Calquence (acalabrutinib) in combination with venetoclax as the first all-oral, fixed-duration regimen for adult patients with chronic lymphocytic leukemia (CLL) and modest lymphocytic lymphoma (SLL). This approval offers a new treatment option for those in the first-line setting, potentially reducing the burden of side effects often associated with continuous regimens.
AMPLIFY Trial Results Drive Approval
The FDA’s decision is based on positive results from the Phase III AMPLIFY trial. Data presented at the American Society of Hematology 2024 Annual Meeting and published in The New England Journal of Medicine demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to chemoimmunotherapy. Specifically, 77% of patients treated with the Calquence combination remained progression-free at three years 1.
The AMPLIFY trial evaluated Calquence in combination with venetoclax, with or without obinutuzumab, against investigator’s choice of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) in adult patients with previously untreated CLL 2. It is the first randomized study to evaluate a fixed-duration regimen of venetoclax with a second-generation Bruton’s tyrosine kinase (BTK) inhibitor 3.
Addressing Unmet Needs in CLL Treatment
CLL is the most common type of leukemia in adults. Approximately 18,500 people in the U.S. Were treated for CLL in the first-line setting in 2024 1. Traditional continuous regimens can lead to burdensome side effects over time.
Jennifer Brown, MD, PhD, Director of the CLL Center of the Division of Hematologic Malignancies, Dana-Farber Cancer Institute, and principal investigator of the AMPLIFY trial, emphasized the benefits of the new treatment option: “The US approval of the Calquence combination offers patients an all-oral, 14-month, fixed-duration treatment option that is highly effective and well-tolerated, and gives physicians greater flexibility to tailor treatment plans for individual patient needs and goals.” 1
About the Therapies
- Calquence (acalabrutinib): A selective Bruton’s tyrosine kinase (BTK) inhibitor.
- Venetoclax: A BCL-2 inhibitor.
Further Research
A related study (NCT05197192) investigated acalabrutinib plus obinutuzumab, acalabrutinib alone, and chlorambucil plus obinutuzumab, showing substantial improvements in PFS for the combination and monotherapy arms compared to standard chemoimmunotherapy 4.