Acalabrutinib Demonstrated Fewer Incidences of Atrial Fibrillation Versus Ibrutinib in Previously Treated Patients With Chronic Lymphocytic Leukemia

Final results from the ELEVATE-RR phase 3 trial comparing acalabrutinib (Calquence, AstraZeneca) against ibrutinib (Imbruvica, Janssen) in adults with previously treated chronic lymphocytic leukemia (CLL) showed acalabrutinib presented with non-inferior progression-free survival (PFS) and significantly fewer events of atrial fibrillation, according to a presentation at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

ELEVATE-RR is the first phase 3 trial comparing 2 Bruton’s tyrosine kinase (BTK) inhibitors in patients with previously treated CLL with presence of 17p deletion or presence of 11q deletion.

During the trial, the investigators found that at the median follow-up point of 40.9 months, the trial met its primary endpoint of PFS non-inferiority versus ibrutinib with a median PFS of 38.4 months in both arms (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.79-1.27).

When assessing the key secondary endpoint of all-grade atrial fibrillation, the investigators observed that patients who were treated with acalabrutinib demonstrated a statistically significant decreased incidence of all-grade atrial fibrillation compared with patients treated with ibrutinib (9.4% [n=25/266] versus 16.0% [n=42/263]; p=0.02). These results are significant because atrial fibrillation can increase the risk of stroke, heart failure, and other heart-related complications.

“Cardiac adverse events are an important consideration for treating chronic lymphocytic leukemia patients with Bruton’s tyrosine kinase inhibitors because they can produce significant morbidity in some cases and also lead patients to discontinue treatment,” said lead investigator John C. Byrd, MD, distinguished university professor, Ohio State University, in a press release. “These data provide compelling evidence that acalabrutinib is a more tolerable option with reduced cardiovascular toxicity and overall fewer discontinuations due to adverse events, giving clinicians further reassurance when prescribing this medicine that patients can stay on treatment while maintaining ongoing control of their disease.”

During the trial, investigators observed a lower frequency of adverse events (AEs) among patients treated with acalabrutinib versus ibrutinib, including lower common AEs, grade 3 or higher AEs, serious AEs, treatment discontinuations due to AEs, and overall cardiac events. Additionally, safety and tolerability of acalabrutinib was found to be consistent with the known profile of acalabrutinib during the trial as well.

Treatment discontinuation occurred due to the occurrence of AEs in 14.7% of patients on acalabrutinib and 21.3% of patients on ibrutinib. Furthermore, serious AEs of any grade occurred among 53.8% of patients on acalabrutinib versus 58.6% of patients receiving ibrutinib.

During the trial, investigators observed that the AEs of clinical interest for acalabrutinib versus ibrutinib included cardiac events (all grade, 24.1%, and 30.0%, respectively); bleeding events (all grade, 38.0% and 51.3%, respectively); hypertension (all grade, 9.4% and 23.2%, respectively); infections (all grade, 78.2% and 81.4%, respectively); interstitial lung disease/pneumonitis (all grade, 2.6% and 6.5%, respectively); and second primary malignancies excluding non-melanoma skin cancer (all-grade, 9.0% and 7.6%, respectively).

Additionally, the investigators found that the median overall survival was not reached in both treatment arms, with 23.5% of patients treated with acalabrutinib and 27.5% of patients treated with ibrutinib experiencing an event (HR of 0.82, 95% CI 0.59-1.15).

“Tolerability is a critical factor in treating patients with chronic lymphocytic leukemia who often remain on medicines for many years and experience multiple comorbidities,” said Dave Fredrickson, executive vice president, oncology business unit, AstraZeneca, in the press release. “The Calquence data at ASCO confirm our confidence in the favorable benefit-risk profile of this medicine, with over 40 months of follow-up.”

REFERENCE

CALQUENCE Demonstrated Fewer Incidences of Atrial Fibrillation Versus Ibrutinib in Previously Treated Patients With Chronic Lymphocytic Leukemia and Sustained Patient Benefit at Four Years in the Front-line Setting. Wilmington, DE: AstraZeneca; June 7, 2021. https://www.businesswire.com/news/home/20210607005222/en/CALQUENCE-Demonstrated-Fewer-Incidences-of-Atrial-Fibrillation-Versus-Ibrutinib-in-Previously-Treated-Patients-With-Chronic-Lymphocytic-Leukemia-and-Sustained-Patient-Benefit-at-Four-Years-in-the-Front-line-Setting. Accessed June 9, 2021.