Study Shows Higher BTKi-Related Toxicity Burden with Ibrutinib, Lower Impact of CV-Related Toxicity with Acalabrutinib

Acalabrutinib is a Bruton tyrosine kinase inhibitor (BTKi) intended for the treatment of adult patients with mantle cell lymphoma who have received at least 1 prior therapy.

A phase 3 trial of acalabrutinib versus ibrutinib demonstrated efficacy and improved tolerability with acalabrutinib in previously treated chronic lymphocytic leukemia (CLL), according to a session presented at the American Society of Hematology Annual Meeting & Exposition 2021.1

Acalabrutinib is a Bruton tyrosine kinase inhibitor (BTKi) intended for the treatment of adult patients with mantle cell lymphoma who have received at least 1 prior therapy. It is also currently indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to an AstraZeneca press release.2

During the study, a major objective of the investigators was to assess the risk-benefit of quality-adjusted time without symptoms or toxicity in relapsed or refractory CLL.2

The patients received oral acalabrutinib 100 mg or ibrutinib 420 mg until disease progression or unacceptable toxicity, with the overall toxicity, exposure-adjusted incidence, and exposure-adjusted time with event durations were assessed for the most common BTKi-related adverse events (AEs). Additionally, atrial fibrillation, hypertension, and bleeding events were further characterized by time to onset, cumulative incidence by Kaplan-Meier method, patient subgroup, and AE management.1

The results showed that out of 533 randomized patients, incidences of any-grade afib/flutter, hypertension, and bleeding were statistically higher with ibrutinib, with higher exposure-adjusted incidence and exposure-adjusted time with event. Further, cases of any-grade diarrhea, arthralgia, contusion, UTI, back pain, muscle spasms, and dyspepsia were statistically higher with ibrutinib, whereas cases of headache and cough were statistically higher with acalabrutinib.1

In terms of any-grade hypertension, the median time to onset was similar for acalabrutinib and ibrutinib, but cumulative incidence was lower for acalabrutinib at 6 months, 12 months, 18 months, and 24 months. Hypertension occurred less frequently with acalabrutinib versus ibrutinib in subgroups of age, prior line of therapy, and among patients without prior history. There was no dose reductions or treatment discontinuations due to hypertension occurred in either arm, and concomitant medication use for hypertension was less common acalabrutinib versus ibrutinib.1

As for any-grade bleeding events, they occurred less frequently with acalabrutinib versus ibrutinib in most subgroups of age and prior line of therapy. Additionally, bleeding events were associated with dose reduction in 3 versus 2 patients in the acalabrutinib versus ibrutinib arms, respectively, leading to treatment discontinuation in 2 versus 4 patients.1

REFERENCES

  1. Seymour JF, Byrd JC, Hillmen P, et al. Characterization of Bruton Tyrosine Kinase Inhibitor (BTKi)-Related Adverse Events in a Head-to-Head Trial of Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia (CLL). Presented at: American Society of Hematology Annual Meeting and Exposition. December 13, 2021 [virtual].
  2. AstraZeneca advances ambition to redefine care for blood cancer at ASH 2021. BusinessWire. November 5, 2021. Accessed December 13, 2021. https://www.businesswire.com/news/home/20211105005227/en/AstraZeneca-Advances-Ambition-to-Redefine-Care-for-Blood-Cancer-at-ASH-2021