Calquence + venetoclax improves survival in untreated CLL

These results will be presented at the American Society of Hematology (ASH) 2024 Annual Meeting in San Diego, CA.

At a median follow up of 41 months, results showed Calquence plus venetoclax reduced the risk of disease progression or death by 35% compared to standard-of-care chemoimmunotherapy (hazard ratio [HR] 0.65; 95% confidence interval [CI] 0.49-0.87; p=0.0038). Calquence plus venetoclax with obinutuzumab demonstrated a 58% reduction in the risk of disease progression or death compared to standard-of-care chemoimmunotherapy (HR 0.42; 95% CI 0.30-0.59; p<0.0001). Median PFS was not reached for either experimental arm versus median PFS of 47.6 months for chemoimmunotherapy.

Interim overall survival (OS) data demonstrated a favourable trend which was nominally statistically significant for Calquence plus venetoclax (HR 0.33; 95% CI 0.18-0.56; p<0.0001), however the OS data were immature at the time of this analysis and the trial will continue to assess OS as a key secondary endpoint.

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: “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.”

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

Both investigational arms demonstrated durable responses, with estimated 36-month PFS rates of 76.5% for Calquence plus venetoclax and 83.1% with the addition of obinutuzumab compared to 66.5% for chemoimmunotherapy. Patients also demonstrated a robust response in both investigational arms with an overall response rate (ORR) of 92.8% for Calquence plus venetoclax and 92.7% with the addition of obinutuzumab, compared to 75.2% for chemoimmunotherapy.

The safety and tolerability of Calquence was consistent with its known safety profile, and no new safety signals were identified. Grade 3 or higher adverse events (AEs) occurred in 53.6% of patients treated with Calquence plus venetoclax, 69.4% of patients treated with Calquence plus venetoclax with obinutuzumab and 60.6% for patients treated with standard-of-care chemoimmunotherapy. The most common Grade 3 or higher AE was neutropenia across all arms, seen in 26.8%, 35.2% and 32.4% of patients respectively. There were over twice as many COVID related deaths in the Calquence plus venetoclax with obinutuzumab arm compared with the Calquence plus venetoclax arm.  

Notably, low rates of tumour lysis syndrome (TLS) were observed in both Calquence arms with events of any grade seen in 0.3% of patients treated with Calquence plus venetoclax and 0.4% with the addition of obinutuzumab, compared to 3.1% for patients treated with chemoimmunotherapy. No cases of clinical TLS were observed across Calquence treatment arms.