Acalabrutinib significantly improved progression-free survival (PFS) outcomes compared with idelalisib plus rituximab (I-R) or bendamustine plus rituximab (B-R) in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL), according to results of a study published in the Journal of Clinical Oncology.
A team of investigators conducted a phase 3, global, randomized, multicenter open-label study (ASCEND; ClinicalTrials.gov Identifier: NCT02970318) to analyze acalabrutinib, a highly selective Bruton tyrosine kinase inhibitor, and to compare its evaluation with I-R and B-R in adults with R/R CLL.
Patients were randomly assigned to receive acalabrutinib monotherapy or investigator’s choice (I-R or B-R) until progressive disease or unacceptable toxicity. The primary endpoint was PFS according to an independent review committee (IRC) in the intent-to-treat population. The secondary endpoints included overall response rate, overall survival, and safety.
In total, 310 patients (median age 67 years) were randomly assigned (1:1) to the treatment groups: 155 received acalabrutinib monotherapy and 155 received investigator’s choice. Of the participants assigned to investigator’s choice, 119 patients were treated with I-R and 36 patients were treated with B-R. Patient demographic and disease characteristics were well balanced at baseline. Overall, the patients had received a median number of 2 prior therapies (range, 1-10).
The median follow-up was 16.1 months; at that time, the acalabrutinib group had a significantly longer median PFS (not reached) compared with the investigator’s choice group (16.5 months; hazard ratio, 0.31; P <.0001). The estimated 12-month PFS was 88% in the acalabrutinib group and 68% in the investigator’s choice group. The IRC-assessed ORR was similar between the 2 groups (81% in the acalabrutinib arm and 75% in the investigator’s choice arm; P =.22). Median OS was not reached in either treatment group.
Overall, 94% of patients had at least 1 adverse event (AE). Grade 3/4 AEs occurred more often with I-R (86%) than with acalabrutinib (45%) or B-R (43%). Serious AEs also occurred more often with I-R (56%) than with acalabrutinib (29%) or B-R (26%).
Death occurred in 10% of patients receiving acalabrutinib, 11% of those receiving I-R, and 14% of those receiving B-R.
The primary limitations of the study were the unblinded treatment assignments, the unbalanced assignments among the 2 treatments in investigator’s choice group, and the absence of an ibrutinib monotherapy arm. The authors also noted that extended follow-up is needed to detect differences in OS, which may be affected by the ability of patients to crossover to receive acalabrutinib.
“These findings suggest the use of acalabrutinib as an effective treatment for patients with R/R CLL (including patients with high-risk disease characteristics), and support the recent approval of acalabrutinib in this setting,” the authors concluded.
Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Ghia P, Pluta A, Wach M, et al. ASCEND: phase III, randomized trial of acalabrutinib versus idelalisib plus rituximab or bendamustine plus rituximab in relapsed or refractory chronic lymphocytic leukemia [published online May 27, 2020]. J Clin Oncol. doi: 10.1200/JCO.19.03355