AstraZeneca's Calquence (acalabrutinib) in combination with venetoclax has demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to standard-of-care chemoimmunotherapy in previously untreated adult patients with chronic lymphocytic leukemia (CLL). These findings come from the AMPLIFY Phase III trial, with results slated for presentation at the American Society of Hematology (ASH) 2024 Annual Meeting. The study offers a potential new treatment approach for CLL, addressing the need for more effective and less toxic therapies.
AMPLIFY Trial Results
After a median follow-up of 41 months, the data showed that Calquence plus venetoclax reduced the risk of disease progression or death by 35% compared to standard chemoimmunotherapy. Furthermore, the combination of Calquence plus venetoclax with obinutuzumab demonstrated an even greater reduction, with a 58% decrease in the risk of disease progression or death compared to standard chemoimmunotherapy. While median PFS was not reached for either experimental arm, the median PFS for chemoimmunotherapy was 47.6 months.
Interim overall survival (OS) data indicated a favorable trend with Calquence plus venetoclax, achieving nominal statistical significance. However, these OS data were immature at the time of analysis, and the trial is ongoing to assess OS as a key secondary endpoint.
Expert Commentary
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, noted, "Based on these impressive data from the AMPLIFY trial, Calquence is the only second-generation BTK inhibitor to demonstrate efficacy in the front-line treatment of patients with chronic lymphocytic leukaemia as both a treat-to-progression and a fixed-duration approach. This advance is an important development for patients and their physicians who seek new options and more flexibility in managing this disease in the long term."
Implications for CLL Treatment
The results from the AMPLIFY trial suggest that a combination therapy of Calquence and venetoclax could offer a more effective and potentially less toxic alternative to traditional chemoimmunotherapy for front-line CLL treatment. The fixed-duration approach may also provide patients and physicians with greater flexibility in managing this chronic disease.
