Progression-Free Survival With Acalabrutinib Non-Inferior to Ibrutinib in High-Risk CLL

In adults with previously treated, high-risk chronic lymphocytic leukemia (CLL), treatment with acalabrutinib (Calquence) was found to be non-inferior to treatment with ibrutinib (Imbruvica) in terms of progression-free survival (PFS), meeting the primary end point of the phase 3 ELEVATE-RR clinical trial (NCT02477696), according to a press release from AstraZeneca.

A statistically significantly lower incidence of atrial fibrillation was also observed with acalabrutinib compared with ibrutinib and there was no difference in the rate of grade 3 or higher infections or Richter’s transformation between the 2 treatment arms, achieving one of the study’s secondary end points of safety. Overall, treatment with acalabrutinib was deemed tolerable in patients with previously treated and high-risk CLL, and the toxicities observed in the study were consistent with the profile previously associated with acalabrutinib.

“With over 40 months of follow-up, today’s results confirm that Calquence, a selective BTK inhibitor, displays superior safety in atrial fibrillation without compromising efficacy. The totality of the data confirm our confidence in the favorable benefit-risk profile of Calquence,” said José Baselga, MD, PhD, executive vice president, Oncology R&D at AstraZeneca, in a statement.

The company plans to present full results from the clinical trial at an upcoming medical meeting.

ELEVATE-RR is a randomized, multicenter, open-label, phase 3 non-inferiority trial. The study enrolled 533 patients and randomized them 1:1 to receive either acalabrutinib or ibrutinib. In the acalabrutinib arm, patients were given a 100-mg dose of the drug orally twice daily. In the ibrutinib arm, the dose administered was 420 mg orally once daily. Treatment was continued until disease progression or unacceptable toxicity in both study arms.

In addition to evaluated PFS and the incidence of atrial fibrillation and Richter’s transformation, the study explored the incidence of treatment-emergent grade 3 or higher infections and overall survival in arm A versus arm B, as an additional secondary end point.

To be eligible for enrollment in the study, patients were required to have a diagnosis of CLL with high-risk prognostic factors, such as a 17p deletion or 11q deletion. Patients were also required to have active disease according to International Workshop on Chronic Lymphocytic Leukemia criteria and be previously treated. In terms of disease characteristics, patients must have had an ECOG performance status of 0 to 2 and meet the criteria for acceptable laboratory values.

The study excluded individuals with central nervous system involvement, present prolymphocytic leukemia, present or historic Richter's syndrome, those with prior exposure to either study drug or a BCR inhibitor, a BCL-2 inhibitor, radiotherapy, toxin-conjugated antibody therapy, or allogeneic stem cell or autologous transplant. Patients were also ineligible to enroll if they had comorbidities or infections that may have interfered with response to therapy.

In CLL, the ELEVATE-RR trial is the first to conduct a comparison between 2 Bruton’s tyrosine kinase inhibitors.

_Reference:

_{Calquence met primary efficacy endpoint in head-to-head trial against ibrutinib in chronic lymphocytic leukemia. News release. AstraZeneca. January 25, 2021. Accessed January 25, 2021. https://bit.ly/3ojnpLS}