Acalabrutinib monotherapy improved progression-free survival (PFS) at 3 years, compared with standard-of-care regimens, in patients with relapsed/refractory chronic lymphocytic leukemia (CLL), according to updated results from the ASCEND study presented at the 2021 American Society of Hematology (ASH) Annual Meeting.
The primary analysis of ASCEND (ClinicalTrials.gov Identifier: NCT02970318) showed that acalabrutinib monotherapy was associated with superior PFS and favorable safety compared with idelalisib plus rituximab (IdR) or bendamustine plus rituximab (BR) in patients with relapsed/refractory CLL at a median follow-up of 16.1 months.
The multicenter, open-label, phase 3 study randomly assigned patients with relapsed/refractory CLL 1:1 to receive acalabrutinib or the investigator’s choice of IdR or BR until disease progression or unacceptable toxicity. Patients who progressed on IdR or BR could cross over to the acalabrutinib monotherapy arm.
A total of 310 patients were included — 155 in the acalabrutinib arm, 119 in the IdR arm, and 36 in the BR arm. Patients had a median age of 67 years (range, 32-90 years), 67.1% were men, 16% had del(17p), 78% had unmutated IGHV, and 42% had Rai stage 3/4. The median duration of exposure was 35.0 months in the acalabrutinib arm, 11.5 months in the IdR arm, and 5.6 months in the BR arm.
At a median follow-up of 36.0 months for the acalabrutinib group and 35.3 months for the IdR/BR group, acalabrutinib was found to significantly prolong investigator-assessed PFS compared with IdR/BR. The median PFS was not reached and 16.8 months, respectively (hazard ratio [HR], 0.29; 95% CI, 0.21-0.41; P <.0001). The 36-month PFS rates were 63% for acalabrutinib and 21% for IdR/BR.
The researchers found similar benefits in PFS for acalabrutinib compared with IdR only (median, not reached vs 16.2 months; HR, 0.31; P <.0001) and compared with BR only (median, not reached vs 18.6 months; HR, 0.25; P <.0001).
High-risk subgroups also had a consistent benefit in PFS with acalabrutinib. In patients who had del(17p), the median PFS was not reached with acalabrutinib and 13.8 months with IdR/BR (HR, 0.13; 95% CI, 0.06-0.3; P <.0001). The 36-month PFS rates were 66% for acalabrutinib and 5% for IdR/BR.
Among patients who had unmutated IGHV, the median PFS was not reached with acalabrutinib and 16.1 months with IdR/BR (HR, 0.30; 95% CI, 0.21-0.42; P <.0001). The 36-month PFS rates were 61% for acalabrutinib and 17% for IdR/BR.
The median overall survival (OS) was not reached in any arm. The 36-month OS rate was 80% for acalabrutinib and 73% for IdR/BR.
The objective response rate (ORR) was 83% with acalabrutinib and 85% with IdR/BR. The ORRs including partial response with lymphocytosis were 92% and 88%, respectively.
The most frequently reported (≥20%) all-grade adverse events (AEs) among patients who received acalabrutinib were headache (23%), neutropenia (23%), diarrhea (21%), and upper respiratory tract infection (20%).
The most common AEs with IdR were diarrhea (53%) and neutropenia (47%), and the most common AEs with BR were neutropenia (34%), fatigue (23%), infusion-related reactions (23%), and nausea (20%).
Serious AEs (SAEs) occurred in 38% of patients in the acalabrutinib arm, 63% of those in the IdR arm, and 26% of those in the BR arm. SAEs reported in 5% of patients or more (in the acalabrutinib, IdR, and BR arms, respectively) were pneumonia (8%, 9%, and 3%), pyrexia (2%, 7%, and 3%), and diarrhea (1%, 15%, and 0%).
AEs led to drug discontinuation in 21% of acalabrutinib recipients, 65% of IdR recipients, and 17% of BR recipients.
These results support the use of acalabrutinib in patients with relapsed/refractory CLL, including patients with high-risk features, according to the investigators.
Disclosures: This study was sponsored by AstraZeneca. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
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Jurczak W, Pluta A, Wach M, et al. Three-year follow-up of the ASCEND trial: acalabrutinib vs rituximab plus idelalisib or bendamustine in relapsed/refractory chronic lymphocytic leukemia. Presented at ASH 2021; December 11-14, 2021. Abstract 393.