Acalabrutinib is Better Tolerated, Noninferior to Ibrutinib in Previously Treated CLL

John C. Byrd, MD

Acalabrutinib (Calquence) was better tolerated, and noninferior to ibrutinib (Imbruvica) in previously treated patients with chronic lymphocytic leukemia (CLL) with del(17p) or del(11q), according to data presented virtually during the 2021 ASCO Annual Meeting.¹

“Acalabrutinib is a more selective inhibitor of [Bruton tyrosine kinase (BTK)] and has been known to have less adverse events (AEs) when compared across trials. [Until] today, no clinical trial has directly compared ibrutinib to acalabrutinib in previously treated CLL. Our trial presented here does this,” said John C. Byrd, MD, professor of hematology at The Ohio State University.

Byrd presented findings from an open-label, randomized, noninferiority, phase 3 trial that compared acalabrutinib and ibrutinib in 533 patients.² Patients were randomized to receive the BTK inhibitor acalabrutinib or ibrutinib until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS), and secondary endpoints were (in hierarchical order): all-grade atrial fibrillation, grade 3 or higher infection, Richter transformation, and overall survival (OS).

Overall, 268 patients received acalabrutinib and 265 received ibrutinib. Median age was 66 years and on average patients had 2 prior lines of therapies; 45.2% of patients had del(17p) and 64.2% had del(11q).

At a median follow-up of 40.9 months, acalabrutinib was noninferior to ibrutinib, with a PFS of 38.4 months in both arms (HR 1.00; 95% CI, 0.79-1.27).

Acalabrutinib was superior in all-grade atrial fibrillation incidence compared to ibrutinib (9.4% versus 16.0%, respectively; P = .023).

“When considering de-novo atrial fibrillation flutter occurring in patients who had never had this before, the difference between ibrutinib and acalabrutinib was greater,” Byrd explained. “Patients with acalabrutinib had a 6.2% incidence, whereas ibrutinib was 14.9%. Among patients developing atrial fibrillation and flutter, prior history of this and other risk factors were more common in the acalabrutinib arm.”

Other end points were comparable between the 2 treatments: 30.8% of patients on acalabrutinib and 30.0% of patients on ibrutinib experienced grade 3 or higher infection; 3.8% of patients on acalabrutinib versus 4.9% of those on ibrutinib had Richter transformation.

Average OS was not reached in either arm. There were 63 (23.5%) deaths in the acalabrutinib arm and 73 (27.5%) in the ibrutinib arm.

When it came to frequent (≥20%) all-grade AEs, the acalabrutinib arm had a lower instance of hypertension than ibrutinib (9.4% vs 23.2%, respectively), arthralgia (15.8% vs 22.8%), and diarrhea (34.3% vs 46.0%). Acalabrutinib, however, did have a higher incidence of headache (34.6% vs 20.2%, respectively) and cough (28.9% vs 21.3%) than ibrutinib.

“Despite a similar [independent review committee] progression-free survival, survival non-statistically favored acalabrutinib with 10 fewer deaths,” Byrd said. “These results demonstrate that acalabrutinib is better tolerated and safer than ibrutinib [and has] similar efficacy in previously treated patients with CLL.”

References

1. Byrd JC, Hillmen P, Ghia P, et. Al. First results of head-to-head trial of acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia. Presented at: 2021 ASCO Annual Meeting; June 4-8, 2021; Virtual. Abstract 7501.
2. Study of acalabrutinib (ACP-196) versus ibrutinib in previously treated subjects with high risk CLL. ClinicalTrials.gov Updated May 20, 2021. Accessed June 2, 2021. https://clinicaltrials.gov/ct2/show/NCT02477696