CALQUENCE Combination Therapy Receives FDA Approval, Signaling a Shift in CLL Treatment
In a landmark decision announced on February 20, 2026, the U.S. Food and Drug Administration (FDA) approved AstraZeneca’s CALQUENCE (acalabrutinib) in combination with venetoclax as a first-line, fixed-duration treatment for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). This approval marks a significant advancement in how CLL is treated, offering patients an all-oral regimen with a defined treatment period.
The Evolution of CLL Treatment: From Continuous to Fixed-Duration
Historically, CLL treatment often involved continuous therapies, which while effective, could lead to long-term side effects. The AMPLIFY Phase III trial demonstrated that a 14-month fixed-duration course of CALQUENCE plus venetoclax resulted in a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to traditional chemoimmunotherapy. Specifically, 77% of patients were progression-free at three years.
Jennifer Brown, MD, PhD, Director of the CLL Center at Dana-Farber Cancer Institute, highlighted the importance of this shift, stating that the new combination offers a highly effective and well-tolerated option, allowing physicians greater flexibility in tailoring treatment plans.
How CALQUENCE Works: Targeting the BTK Protein
CALQUENCE is a second-generation Bruton tyrosine kinase (BTK) inhibitor. BTK plays a crucial role in the growth and survival of cancerous B cells. By inhibiting BTK, CALQUENCE helps reduce the proliferation of these cells. It maintains median steady-state BTK occupancy of ≥95% over 12 hours.
Understanding the AMPLIFY Trial Results
The AMPLIFY trial, a randomized, global Phase III study, compared CALQUENCE plus venetoclax, CALQUENCE plus venetoclax with obinutuzumab, and standard chemoimmunotherapy. The primary endpoint was PFS, and secondary endpoints included overall survival (OS) and undetectable measurable residual disease. The trial included patients from 27 countries.
The most common adverse reactions observed in patients receiving CALQUENCE plus venetoclax included headache, diarrhea, and musculoskeletal pain. Serious adverse reactions occurred in 25% of patients, with COVID-19 being the most frequent.
Safety Considerations and Potential Side Effects
While CALQUENCE offers a promising treatment option, it’s important to be aware of potential safety concerns. These include:
- Serious and Opportunistic Infections: Fatal and serious infections have been reported.
- Hemorrhage: Fatal and serious bleeding events have occurred.
- Cytopenias: CALQUENCE can cause decreases in blood cell counts.
- Second Primary Malignancies: An increased risk of developing other cancers has been observed.
- Cardiac Arrhythmias: Irregular heartbeats have been reported.
- Hepatotoxicity: Liver injury can occur.
Patients should be closely monitored for signs and symptoms of these adverse events.
Drug Interactions and Special Populations
CALQUENCE has specific drug interactions to consider. Strong CYP3A inhibitors should be avoided, while moderate CYP3A inhibitors require dosage adjustments. Strong CYP3A inducers should likewise be avoided or require increased CALQUENCE dosage. Avoid employ in patients with severe hepatic impairment.
Pregnancy testing is recommended for women of reproductive potential, and effective contraception should be used during treatment and for one week afterward. Breastfeeding is not recommended during treatment or for two weeks after the last dose.
The Future of CLL Treatment: What’s Next?
AstraZeneca is actively evaluating CALQUENCE in combination with other therapies for various B-cell blood cancers, including mantle cell lymphoma and diffuse large B-cell lymphoma. The company’s focus on oncology aims to provide cures for cancer in every form, driven by scientific innovation.
FAQ
Q: What is CLL?
A: Chronic lymphocytic leukemia is the most common type of leukemia in adults, characterized by an accumulation of abnormal lymphocytes.
Q: What is a BTK inhibitor?
A: A BTK inhibitor, like CALQUENCE, targets and blocks the Bruton tyrosine kinase protein, which is essential for the growth of cancerous B cells.
Q: What are the potential side effects of CALQUENCE?
A: Potential side effects include infections, bleeding, cytopenias, second primary malignancies, cardiac arrhythmias, and liver injury.
Q: Is CALQUENCE a continuous therapy?
A: The recent FDA approval is for a fixed-duration treatment course of 14 cycles.
Q: Where can I find more information about CALQUENCE?
A: Visit www.calquence.com or consult with your healthcare provider.
Did you grasp? In 2024, an estimated 18,500 people were treated for CLL in the 1st-line setting in the US.
Pro Tip: Discuss all potential drug interactions with your doctor before starting CALQUENCE.
Have questions about CLL treatment options? Share your thoughts in the comments below!
