AstraZeneca’s Fixed-Duration Calquence Regimen Gains EU Approval for First-Line Treatment of Chronic Lymphocytic Leukaemia
AstraZeneca has received European Union (EU) approval for a fixed-duration combination therapy using its Bruton’s tyrosine kinase (BTK) inhibitor Calquence (acalabrutinib) for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL). The regimen combines Calquence with venetoclax, with or without the anti-CD20 monoclonal antibody obinutuzumab, and represents a significant advancement in the treatment paradigm for newly diagnosed CLL patients in Europe.
This decision by the European Commission (EC) comes after a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) and is grounded in robust data from the pivotal AMPLIFY Phase III clinical trial. The results of this study were first unveiled at the 2024 American Society of Hematology (ASH) Annual Meeting and simultaneously published in The New England Journal of Medicine, reinforcing their impact and scientific significance.
Key Findings from the AMPLIFY Study
The AMPLIFY trial was a multicenter, randomized, controlled Phase III study designed to evaluate the efficacy and safety of fixed-duration Calquence-based regimens compared with traditional chemoimmunotherapy in previously untreated CLL patients. Participants were assigned to receive either:
- Calquence + venetoclax (AV)
- Calquence + venetoclax + obinutuzumab (AVO)
- Chemoimmunotherapy (either fludarabine-cyclophosphamide-rituximab [FCR] or bendamustine-rituximab [BR], depending on physician’s choice)
The trial demonstrated compelling improvements in progression-free survival (PFS) with the Calquence regimens:
- 77% of patients on the AV arm remained progression-free at three years
- 83% of patients on the AVO arm achieved three-year PFS
- In contrast, only 67% of those receiving standard chemoimmunotherapy were progression-free at the same time point
Notably, median PFS was not reached in either experimental arm by the time of analysis, indicating sustained disease control, while the median PFS in the chemoimmunotherapy arm was 47.6 months.
Risk of disease progression or death was significantly reduced in both experimental arms:
- The AV regimen showed a 35% reduction in risk (Hazard Ratio [HR]: 0.65; 95% Confidence Interval [CI]: 0.49–0.87; p = 0.0038)
- The AVO regimen demonstrated a 58% reduction (HR: 0.42; 95% CI: 0.30–0.59; p < 0.0001)
These data underscore the clinical benefit of fixed-duration, chemotherapy-free treatment approaches in CLL, an area where traditional regimens have long relied on continuous or indefinite therapy models associated with cumulative toxicities and resistance.
The Burden of Chronic Lymphocytic Leukaemia in Europe
CLL is the most common form of leukaemia in adults, typically affecting older individuals. It is characterized by the gradual accumulation of dysfunctional lymphocytes, leading to immune system dysfunction and, in advanced cases, bone marrow failure. According to estimates, approximately 27,000 people were newly diagnosed with CLL across five major European countries — the UK, France, Germany, Spain, and Italy — in 2024. This number underscores the urgency of expanding access to effective, tolerable, and convenient treatment options.
Clinical Perspective: Expert Commentary
Dr. Barbara Eichhorst, Professor at University Hospital Cologne and investigator in the AMPLIFY trial, emphasized the clinical value of the approval:
“For patients diagnosed with chronic lymphocytic leukaemia, this approval provides a new option in the first-line setting that may help to minimize long-term side effects and reduce drug resistance as they may occur with continuous treatment. A fixed-duration regimen is appealing to patients and helps with adherence during the treatment period.”
Her remarks highlight a growing preference in oncology for time-limited treatment strategies that achieve durable responses while avoiding the risks and burdens associated with prolonged therapy — including cumulative toxicity, immune suppression, and increased financial strain.
AstraZeneca’s Strategic Vision
From the company’s standpoint, this approval reinforces AstraZeneca’s expanding role in hematologic oncology and positions Calquence as a versatile and foundational agent in CLL treatment regimens. Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Haematology Business Unit, commented:
“Today’s approval brings a new fixed-duration treatment option to patients with previously untreated chronic lymphocytic leukaemia across Europe. Calquence plus venetoclax is the first and only all-oral combination treatment option with a second-generation BTK inhibitor approved in the EU and provides patients and their physicians more flexibility in managing this incurable blood cancer.”
His statement spotlights one of the defining features of the AV regimen — its all-oral formulation, which simplifies administration and potentially enhances patient convenience and adherence. The inclusion of acalabrutinib, a second-generation, highly selective BTK inhibitor, allows for a more targeted approach with fewer off-target effects compared to earlier-generation BTK inhibitors.
Safety Profile and Tolerability
Safety is a paramount concern in long-term cancer therapy, especially in CLL, where many patients live for years post-diagnosis. The AMPLIFY trial confirmed that Calquence’s safety profile remained consistent with previous findings. Importantly, no new safety signals were observed, which is reassuring as it supports the feasibility of expanding use to broader patient populations, including the elderly and those with comorbidities.
Global Regulatory Reviews Underway
With the EC’s authorization now secured, AstraZeneca is pushing forward with regulatory submissions in other markets. Applications for fixed-duration Calquence-based regimens are currently under review in several countries worldwide, signaling AstraZeneca’s intent to make this approach a global standard of care for first-line CLL.
This aligns with a broader industry trend emphasizing innovative combinations and optimized durations to balance efficacy with quality of life in oncology. Fixed-duration treatment strategies represent a major shift from conventional thinking and may reshape how clinicians treat CLL and other hematologic malignancies in the years to come.
The European approval of AstraZeneca’s Calquence plus venetoclax (with or without obinutuzumab) for fixed-duration first-line treatment in CLL marks a milestone in the evolution of care for this chronic disease. Armed with strong efficacy data, an oral administration route, and a time-limited protocol, this regimen addresses both clinical and quality-of-life priorities for patients and providers alike. It also broadens the therapeutic arsenal available to oncologists, further strengthening the case for personalized, adaptive, and patient-centered approaches to managing chronic lymphocytic leukaemia.
As regulatory agencies in other countries evaluate the AMPLIFY data, the momentum behind this combination therapy continues to build — offering new hope for thousands of patients newly confronting a CLL diagnosis.
