KEY TAKEAWAYS
- Phase 3 ASCEND trial compared acalabrutinib vs IdR or BR in R/R CLL patients.
- The primary aim was to evaluate progression-free survival (PFS).
- Patients received acala 100 mg BID until progression, unacceptable toxicity, or INV’s choice of IdR or BR.
- Acala significantly prolonged INV-assessed PFS vs IdR/BR with acceptable tolerability at ~4 years of follow-up in R/R CLL patients.
For individuals with chronic lymphocytic leukemia (CLL), the next-generation, highly selective, covalent Bruton tyrosine kinase (BTK) inhibitor acalabrutinib (acala) is an option. In the primary analysis of ASCEND (median follow-up 16.1 mo), patients with relapsed/refractory (R/R) CLL were compared to those receiving idelalisib (Id) plus rituximab (R) (IdR) or bendamustine (B) plus R (BR).
In this multicenter, randomized, open-label, phase 3 study (NCT02970318), pts with R/R CLL received oral (PO) acala 100 mg BID until progression or unacceptable toxicity or investigator’s (INV) choice of IdR (Id: 150 mg PO BID until progression or unacceptable toxicity; R: 375 mg/m2 x1 then 500 mg/m2 IV [8 total infusions]) or BR (B: 70 mg/m2 IV; R: 375 mg/m2 x1 then 500 mg/m2 IV [6 cycles]). Overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety were evaluated.
The median age of the 310 pts was 67 years old, 15% had del(17p), 74% had unmutated IGHV, and 42% were in Rai stages 3/4. Compared with IdR/BR, acala significantly increased INV-assessed PFS at a median follow-up of 46.5 months (median not reached [NR] vs 16.8 months; P0.0001); 42-month PFS rates for acala were 62% versus 19%. Patients with del(17p) had a median PFS of not reached (acala) against 13.8 months (IdR/BR; P0.0001). Median PFS in patients with unmutated IGHV was NR (acala) versus 16.2 months (IdR/BR; P0.0001). The median overall survival (OS) was not reached in either treatment group, and at 42 months, the OS rates were 78% (acala) and 65% (IdR/BR). The overall response rate was 83% for acala and 84% for IdR/BR (92% for acala and 88% for IdR/BR when including a partial response with lymphocytosis). Patients with acala, IdR, and BR all had higher rates of AE-related medication discontinuation (23%, 67%, and 17%). All-grade atrial fibrillation/flutter was more common in the acala group (8% vs 3%), as were all-grade hypertension (8% vs 5%), all-grade severe haemorrhage (3% vs 3%), and grade ≥3 infections (29% vs 29%). Acala’s efficacy in R/R CLL remained comparable to standard-of-care regimens, and the drug was well tolerated throughout the 4-year follow-up period.
Source: https://library.ehaweb.org/eha/2022/eha2022-congress/357529/paolo.ghia.acalabrutinib.vs.rituximab.plus.idelalisib.or.bendamustine.in.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Amedia%3D3%2Ace_id%3D2233%2Aot_id%3D26848%2Amarker%3D1769%2Afeatured%3D17676
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02970318
Paolo Ghia, Andrzej Pluta, Malgorzata Wach, Daniel Lysak, Martin Simkovic, Iryna Kriachok, Arpad Illes, Javier de la Serna, Sean Dolan, Philip Campbell, Gerardo Musuraca, Abraham Jacob, Eric Avery, Jae Hoon Lee, Ganna Usenko, Min Hui Wang, Ting Yu, Wojciech Jurczak (Abstract release date: 05/26/22) EHA Library. Ghia P. 06/10/2022; 357529; P668
