Acalabrutinib ( Calquence ) is a next-generation, highly selective, covalent Bruton tyrosine kinase inhibitor approved for patients with chronic lymphocytic leukemia ( CLL ) including those with relapsed / refractory ( R/R ) CLL.
The efficacy and safety of Acalabrutinib alone vs Idelalisib ( Zydelig ) plus Rituximab [ IdR ] or Bendamustine plus Rituximab were shown in patients with relapsed / refractory chronic lymphocytic leukemia in a preplanned interim analysis of ASCEND.
Researchers have reported final results.
In this randomized, multicenter, phase 3, open-label study, patients with relapsed / refractory chronic lymphocytic leukemia were randomized 1:1 to receive oral ( PO ) Acalabrutinib 100 mg BID or investigator’s choice of Idelalisib plus Rituximab ( Idelalisib: 150 mg PO [ per os ] BID until progression or toxicity; Rituximab: 375 x1 then 500 mg/m2 intravenously [ IV ] for 8 total infusions ) or Bendamustine plus Rituximab [ BR ] ( Bendamustine: 70 mg/m2 IV and Rituximab: 375 x1 then 500 mg/m2 IV for 6 total cycles ) until progression or toxicity.
Progression-free survival ( PFS ), overall survival ( OS ), overall response rate ( ORR ), and safety were assessed.
310 patients ( Acalabrutinib, n=155; Idelalisib plus Rituximab, n=119; Bendamustine plus Rituximab, n=36 ) were enrolled ( median age: 67 years; del(17p) 16%, del(11q) 27%, Rai stage 3/4 42% ).
At a median follow-up of 22.0 months, Acalabrutinib significantly prolonged investigator-assessed PFS vs IdR/BR ( median: not reached vs 16.8 m; hazard ratio, HR=0.27, P less than 0.0001 ); 18-months PFS rates were 82% for Acalabrutinib and 48% for IdR/BR.
18-months OS rate was 88% for both treatment regimens. ORR was 80% with Acalabrutinib vs 84% with IdR/BR ( ORR + partial response with lymphocytosis: 92% vs 88%, respectively ).
Adverse effects led to drug discontinuation in 16% of Acalabrutinib, 56% of Idelalisib plus Rituximab, and 17% of Bendamustine plus Rituximab patient.
Adverse effects of interest included atrial fibrillation ( Acalabrutinib 6%, IdR/BR 3% ), major hemorrhage ( all grade; Acalabrutinib 3%, IdR/BR 3% ), grade greater than or equal to 3 infections ( Acalabrutinib 20%, IdR/BR 25% ), and second primary malignancies excluding non-melanoma skin cancer ( Acalabrutinib 5%, IdR/BR 2% ).
In conclusion, final ASCEND results with additional follow-up have confirmed earlier findings and have supported the favorable efficacy and safety of Acalabrutinib compared with standard-of-care regimens in patients with relapsed / refractory chronic lymphocytic leukemia. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020