December 12, 2021: “Updated results from the ASCEND Phase III trial showed AstraZeneca’s Calquence (acalabrutinib) maintained a statistically significant progression-free survival (PFS) benefit at three years compared to investigator’s choice of rituximab combined with either idelalisib (IdR) or bendamustine (BR) in adults with relapsed or refractory chronic lymphocytic leukaemia (CLL), the most common type of leukaemia in adults.
These data, presented at the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition, demonstrated Calquence reduced the risk of disease progression or death by 71% versus IdR/BR as assessed by investigators at three years (based on a hazard ratio [HR] of 0.29; 95% confidence interval [CI]: 0.21-0.41; p<0.0001).
Similar clinical benefits were observed in an exploratory analysis comparing each regimen with Calquence. Safety and tolerability of Calquence were consistent with earlier findings, with no new safety signals identified.
Additional safety analyses from the ELEVATE-RR Phase III trial were also presented at ASH to further characterise adverse events (AEs) related to treatment with Bruton’s tyrosine kinase (BTK) inhibitors Calquence and ibrutinib.
Overall, patients on ibrutinib experienced a 37% higher burden of AEs of any grade versus patients on Calquence.
For any grade atrial fibrillation/flutter, a key secondary endpoint in the ELEVATE-RR trial, median time to onset was longer for Calquence versus ibrutinib (28.8 versus 16.0 months), and cumulative incidence was lower at all timepoints from six months through two years.
Additionally, the ELEVATE-RR Phase III trial showed incidence of all-grade atrial fibrillation/flutter was lower for Calquence across subgroups of age, prior line of therapy and among patients without prior history of heart complications.
Atrial fibrillation is an irregular heart rate that can increase the risk of stroke, heart failure and other heart-related complications.
John F. Seymour, MBBS PhD, Peter MacCallum Centre and the Royal Melbourne Hospital, and a lead investigator on the ELEVATE-RR trial, said: “Patients with relapsed or refractory chronic lymphocytic leukaemia face limited options to successfully manage their disease, as they are often older and dealing with significant comorbidities.
The risk of cardiac adverse events is an important consideration, especially for treatment with Bruton’s tyrosine kinase inhibitors because they can produce significant morbidity in some casesand also lead patients to discontinue treatment.
The ELEVATE-RR data provide compelling evidence that acalabrutinib is a more tolerable option with reduced cardiovascular toxicity, giving clinicians further reassurance when prescribing this medicine that fewer patients will need to cease treatment due to adverse events, thus maintaining ongoing control of their disease, even in this complex setting.”
Anas Younes, Senior Vice President, Haematology R&D, AstraZeneca, said: “These impressive new long-term data support Calquence as the preferred therapy for the most common type of leukaemia in adults, with favourable safety compared to the current standards of care.
The totality of the ASCEND and ELEVATE-RR data, in addition to data introducing a new tablet formulation for patients who need alternative methods of taking Calquence, continues to reinforce the positive experience that this medicinecan deliver for patients with chronic lymphocytic leukaemia.”