At the American Society of Clinical Oncology (ASCO) Annual Meeting in 2022, we received the four-year follow-up data update on the ASCEND trial.
This trial compared acalabrutinib (acala) to the treating doctor’s choice of rituximab plus idelalisib (IdR) or bendamustine (BR) in relapsed/refractory (R/R) chronic lymphocytic leukemia.
- 310 pts (acala, n=155; IdR, n=119; BR, n=36) were randomized (median age 67 year; del(17p) 15%, unmutated IGHV 74%, Rai stage 3/4 42%).
- Acalabrutinib significantly prolonged progression-free survival (PFS) versus (vs) IdR/BR.
- The 42-month PFS rates were 62% for acalabrutinib vs. 22% for IdR and 5% for BR.
- In patients with del(17p), median PFS was not reached for acalabrutinib vs. 13.8 months for IdR/BR.
- PFS was more favorable for acalabrutinib in all subgroups analyzed, including age, gender, the status of IGHV mutation, TP53, and (del)17p.
- Median overall survival (OS) was not reached in both arms; 42-mo OS rates were 78% for acalabrutinib vs. 65% for IdR/BR.
- Overall Response rate (ORR) was 83% for acalabrutinib vs. 84% for IdR/BR, reminding us that we are interested not in how many responded but in how deep and duration those responses were.
- Adverse events led to drug discontinuation in 23% of acalabrutinib, 67% of IdR, and 17% of BR patients.
- Adverse events of particular clinical interest (acalabrutinib vs IdR/BR) included atrial fibrillation/flutter (8% vs 3), hypertension (8% vs 5%), major hemorrhage (3% vs 3%), and severe or grade ≥3 infections (29% vs 29%).
To no one’s surprise, acalabrutinib was a better choice for patients regarding progression-free survival. It came with fewer side effects leading to drug discontinuation compared with bendamustine plus rituximab or with idelalisib with rituximab in relapsed/refractory CLL patients. There was no statistically significant difference in overall survival, though there was a trend favoring acalabrutinib. There is every reason to be confident, based on more mature practice changing Alliance trial with ibrutinib (plus or minus rituximab) versus BR, that future analysis will prove that choosing acalabrutinib also increases how long those with CLL live.
While not groundbreaking, it is confidence-building to see longer follow-up data of approximately four years for acalabrutinib and another novel agent used as one of the comparators.
Watch my monologue on the abstract below. The slides in the video can be accessed here.
Here is the link to the actual ASCO abstract: Acalabrutinib versus rituximab plus idelalisib or bendamustine in relapsed/refractory chronic lymphocytic leukemia: ASCEND results at 4 years of follow-up.
Stay strong. We are all in this together.
Brian Koffman MDCM (retired) MS Ed (he, him, his)
Co-Founder, Executive VP, and Chief Medical Officer, CLL Society, Inc.