AstraZeneca's Calquence-Venetoclax Combo Boosts Chronic Lymphocytic Leukaemia Outcomes

AstraZeneca's Calquence (acalabrutinib), when combined with venetoclax, has delivered promising results in the Phase III AMPLIFY trial for treating adults with chronic lymphocytic leukaemia (CLL). The findings will be presented at the 2024 American Society of Hematology (ASH) Annual Meeting in San Diego. The presentation will significantly improve progression-free survival (PFS) compared to standard chemoimmunotherapy.

With a median follow-up of 41 months, the combination of Calquence and venetoclax reduced the risk of disease progression or death by 35%. Adding obinutuzumab to this regimen further decreased the risk by 58%. Median PFS was not reached for either experimental group, compared to 47.6 months for chemoimmunotherapy. Interim overall survival (OS) data also showed encouraging trends, with a 67% reduction in the risk of death for Calquence plus venetoclax. However, the OS data remains immature and requires further evaluation.

Jennifer R. Brown, MD, PhD, Director of the CLL Center of the Division of Hematologic Malignancies, Dana-Farber Cancer Institute, and the Worthington and Margaret Collette Professor of Medicine at Harvard Medical School, and principal investigator of the trial, said in a statement, “Chronic lymphocytic leukaemia is considered an incurable cancer and patients live with the disease and the long-term effects of their treatments for many years. The AMPLIFY results show the promise of a new all-oral fixed-duration therapy approach which would allow patients to take breaks from treatment, reducing the risk of long-term adverse events and drug resistance.”

Durability of response was evident, with 36-month PFS rates of 76.5% for Calquence and venetocla, and 83.1% when obinutuzumab was added, compared to 66.5% for chemoimmunotherapy. The overall response rates were similarly robust, at 92.8% and 92.7% for the two experimental arms, respectively, versus 75.2% for chemoimmunotherapy.

Safety results aligned with Calquence’s established profile, with no new safety concerns identified. Grade 3 or higher adverse events occurred in 53.6% of patients on Calquence and venetoclax, 69.4% with the addition of obinutuzumab, and 60.6% in the chemoimmunotherapy group. Neutropenia was the most common severe side effect across all groups. COVID-related deaths were notably higher in the obinutuzumab arm.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, commented, “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.” 

Tumor lysis syndrome (TLS), a significant treatment concern, was rare in the Calquence arms, with rates of 0.3% and 0.4% for the two experimental groups compared to 3.1% with chemoimmunotherapy. No cases of clinical TLS occurred in patients receiving Calquence. Calquene is globally approved for CLL and small lymphocytic lymphoma (SLL) in various settings and has treated over 85,000 patients worldwide. These findings further reinforce its role as a transformative option for CLL treatment.