ACALABRUTINIB VS IDELALISIB PLUS RITUXIMAB (IDR) OR BENDAMUSTINE PLUS RITUXIMAB (BR) IN RELAPSED/REFRACTORY (R/R) CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): ASCEND FINAL RESULTS
Author(s): ,
Paolo Ghia
Affiliations:
Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele,Milano,Italy
,
Andrzej Pluta
Affiliations:
Department of Hematological Oncology,Oncology Specialist Hospital,Brzozow,Poland
,
Malgorzata Wach
Affiliations:
Department of Hemato-Oncology and Bone Marrow Transplantation,Medical University of Lublin,Lublin,Poland
,
Daniel Lysak
Affiliations:
Fakultní Nemocnice Plzen,Pilsen,Czech Republic
,
Tomas Kozak
Affiliations:
Fakultní Nemocnice Královske Vinohrady,Prague,Czech Republic
,
Martin Simkovic
Affiliations:
University Hospital Hradec Kralove, Charles University,Hradec Kralove,Czech Republic
,
Polina Kaplan
Affiliations:
City Clinical Hospital No. 4 DCC,Dnipro,Ukraine
,
Iryna Kraychok
Affiliations:
National Cancer Institute,Kiev,Ukraine
,
Arpad Illes
Affiliations:
Department of Hematology,University of Debrecen, Faculty of Medicine,Debrecen,Hungary
,
Javier de la Serna
Affiliations:
Hospital Universitario 12 de Octubre,Madrid,Spain
,
Sean Dolan
Affiliations:
Saint John Regional Hospital, University of New Brunswick,New Brunswick,Canada
,
Philip Campbell
Affiliations:
Barwon Health, University Hospital Geelong,Victoria,Australia
,
Gerardo Musuraca
Affiliations:
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori,Meldola,Italy
,
Abraham Jacob
Affiliations:
The Royal Wolverhampton NHS Trust,Wolverhampton,United Kingdom
,
Eric Avery
Affiliations:
Nebraska Hematology Oncology,Lincoln,United States
,
Jae Hoon Lee
Affiliations:
Gachon University Gil Medical Center,Incheon,Korea, Republic Of
,
Denise Wang
Affiliations:
Acerta Pharma,South San Francisco,United States
,
Priti Patel
Affiliations:
Acerta Pharma,South San Francisco,United States
,
Cheng Quah
Affiliations:
Acerta Pharma,South San Francisco,United States
Wojciech Jurczak
Affiliations:
Maria Sklodowska-Curie National Institute of Oncology,Krakow,Poland
EHA Library. Ghia P. 06/12/20; 294979; S159
Dr. Paolo Ghia
Dr. Paolo Ghia
Contributions
Abstract

Abstract: S159

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: CLL - Targeted therapy I

Background
Acalabrutinib is a next-generation, highly selective, covalent Bruton tyrosine kinase inhibitor approved for patients with CLL including those with R/R CLL.

Aims
The efficacy and safety of acalabrutinib alone versus IdR or BR were shown in patients with R/R CLL in a preplanned interim analysis of ASCEND; final results are reported herein.

Methods
In this randomized, multicenter, phase 3, open-label study (NCT02970318), patients with R/R CLL were randomized 1:1 to receive oral (PO) acalabrutinib 100 mg twice daily (BID) or investigator’s (INV) choice of IdR (Id: 150 mg PO BID until progression or toxicity; R: 375 x1 then 500 mg/m2 intravenously [IV] for 8 total infusions) or BR (B: 70 mg/m2 IV and R: 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. All patients provided informed consent.

Results
A total of 310 patients (acalabrutinib, n=155; IdR, n=119; BR, n=36) were enrolled (median age: 67 y; del(17p) 16%, del(11q) 27%, Rai stage 3/4 42%). At a median follow-up of 22.0 months, acalabrutinib significantly prolonged INV-assessed PFS vs IdR/BR (median: not reached vs 16.8 months; hazard ratio: 0.27, P<0.0001); 18-month PFS rates were 82% for acalabrutinib and 48% for IdR/BR. The 18-month OS rate was 88% for both treatment regimens. The ORR was 80% with acalabrutinib versus 84% with IdR/BR; ORR including partial response with lymphocytosis was 92% versus 88%, respectively. Common adverse events (AEs) are listed in the Table. AEs led to drug discontinuation in 16% of acalabrutinib, 56% of IdR, and 17% of BR patients. AEs of interest included atrial fibrillation (acalabrutinib 6%, IdR/BR 3%), major hemorrhage (all grade; acalabrutinib 3%, IdR/BR 3%), grade ≥3 infections (acalabrutinib 20%, IdR/BR 25%), and second primary malignancies excluding non-melanoma skin cancer (acalabrutinib 5%, IdR/BR 2%).

Conclusion
Final ASCEND results with additional follow-up confirm earlier findings and support the favorable efficacy and safety of acalabrutinib compared with standard-of-care regimens in patients with R/R CLL.

Session topic: 06. Chronic lymphocytic leukemia and related disorders - Clinical

Keyword(s): Chronic lymphocytic leukemia

Abstract: S159

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: CLL - Targeted therapy I

Background
Acalabrutinib is a next-generation, highly selective, covalent Bruton tyrosine kinase inhibitor approved for patients with CLL including those with R/R CLL.

Aims
The efficacy and safety of acalabrutinib alone versus IdR or BR were shown in patients with R/R CLL in a preplanned interim analysis of ASCEND; final results are reported herein.

Methods
In this randomized, multicenter, phase 3, open-label study (NCT02970318), patients with R/R CLL were randomized 1:1 to receive oral (PO) acalabrutinib 100 mg twice daily (BID) or investigator’s (INV) choice of IdR (Id: 150 mg PO BID until progression or toxicity; R: 375 x1 then 500 mg/m2 intravenously [IV] for 8 total infusions) or BR (B: 70 mg/m2 IV and R: 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. All patients provided informed consent.

Results
A total of 310 patients (acalabrutinib, n=155; IdR, n=119; BR, n=36) were enrolled (median age: 67 y; del(17p) 16%, del(11q) 27%, Rai stage 3/4 42%). At a median follow-up of 22.0 months, acalabrutinib significantly prolonged INV-assessed PFS vs IdR/BR (median: not reached vs 16.8 months; hazard ratio: 0.27, P<0.0001); 18-month PFS rates were 82% for acalabrutinib and 48% for IdR/BR. The 18-month OS rate was 88% for both treatment regimens. The ORR was 80% with acalabrutinib versus 84% with IdR/BR; ORR including partial response with lymphocytosis was 92% versus 88%, respectively. Common adverse events (AEs) are listed in the Table. AEs led to drug discontinuation in 16% of acalabrutinib, 56% of IdR, and 17% of BR patients. AEs of interest included atrial fibrillation (acalabrutinib 6%, IdR/BR 3%), major hemorrhage (all grade; acalabrutinib 3%, IdR/BR 3%), grade ≥3 infections (acalabrutinib 20%, IdR/BR 25%), and second primary malignancies excluding non-melanoma skin cancer (acalabrutinib 5%, IdR/BR 2%).

Conclusion
Final ASCEND results with additional follow-up confirm earlier findings and support the favorable efficacy and safety of acalabrutinib compared with standard-of-care regimens in patients with R/R CLL.

Session topic: 06. Chronic lymphocytic leukemia and related disorders - Clinical

Keyword(s): Chronic lymphocytic leukemia

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