ASCEND PHASE 3 STUDY OF ACALABRUTINIB VS INVESTIGATOR’S CHOICE OF RITUXIMAB PLUS IDELALISIB (IDR) OR BENDAMUSTINE (BR) IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)
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 Plzeň,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:
Dnipropetrovsk City Clinical Hospital No. 4,Dnipropetrovsk,Ukraine
,
Iryna Kraychok
Affiliations:
National Cancer Institute,Kiev,Ukraine
,
Arpad Illes
Affiliations:
Faculty of Medicine, Department of Hematology,University of Debrecen,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
,
Phillip Campbell
Affiliations:
Barwon Health, University Hospital Geelong,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
,
EJ Avery
Affiliations:
Nebraska Hematology Oncology,Lincoln,United States
,
Jae Hoon Lee
Affiliations:
Gachon University Gil Medical Center,Incheon,Korea, Republic Of
,
Wei Liang
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:
Department of Hematology, Jagiellonian University Medical College,Krakow,Poland
EHA Library. Ghia P. Jun 16, 2019; 273259; LB2606
Dr. Paolo Ghia
Dr. Paolo Ghia
Contributions
Abstract
This abstract is embargoed until Saturday, June 15, 08:30 local time.

Abstract: LB2606

Type: Oral Presentation

Presentation during EHA24: On Sunday, June 16, 2019 from 12:30 - 12:45

Location: Hall 5

Background

Most patients (pts) with CLL respond to initial therapies though nearly all relapse and require subsequent therapy. More effective and tolerable treatments are needed for R/R CLL. Acalabrutinib is a highly selective, potent, covalent Bruton tyrosine kinase inhibitor with clinical benefit in pts with R/R CLL.

Aims

In this randomized, global, multicenter, open-label Phase 3 study (CL-309; ASCEND; NCT02970318), the efficacy and safety of acalabrutinib monotherapy was evaluated vs investigator choice of IdR or BR in R/R CLL.

Methods

Eligible pts with R/R CLL were randomized 1:1 to receive 100 mg oral acalabrutinib BID until progression vs IdR (Id 150 mg oral BID in combination with up to 8 IV infusions of R [375 or 500 mg/m2]) or BR (70 mg/m2 IV B on Day 1 and 2 of each cycle combined with R [375 or 500 mg/m2 IV] on Day 1 of each 28-d cycle for up to 6 cycles). Pts were stratified by del(17p) status (y vs n), ECOG status (0-1 vs 2) and prior lines of therapy (1-3 vs ≥4). The primary endpoint was progression-free survival (PFS) assessed by independent review committee (IRC). Secondary endpoints included overall survival (OS), IRC-assessed overall response rate (ORR) and safety. Pts with confirmed progression on IdR/BR could cross over to receive acalabrutinib monotherapy.

Results

310 pts were randomized to acalabrutinib (n=155) or IdR/BR (n=155 [IdR, n=119; BR, n=36]); median age was 67 y (range, 32-90); 16% had del(17p); 27% had del(11q); 42% had Rai stage III/IV CLL. Median (range) no. of prior therapies was 1 (1-8) for acalabrutinib and 2 (1-10) for IdR/BR; pts received prior purine analogues (69%), alkylating agents (85%) and anti-CD20 antibodies (80%). Discontinuation due to AEs occurred in 11% of pts on acalabrutinib vs 49% Id, 12% R in IdR, 11% B and 17% R in BR. At a median follow-up of 16.1 mo, acalabrutinib significantly prolonged IRC-assessed PFS vs IdR/BR (median NR vs 16.5 mo; HR 0.31, 95% CI 0.20-0.49, P<.0001); this represents a 69% reduction in risk of progression or death (Figure). PFS rates at 12 mo were 88% with acalabrutinib and 68% with IdR/BR. PFS improvement with acalabrutinib (vs IdR/BR) was seen across subgroups including del(17p), TP53 mutation and Rai stage. IRC-assessed ORR was not significantly different with acalabrutinib vs IdR/BR (81% vs 75%, respectively; p<.22). 12-mo OS rates were 94% and 91% (with 15 and 18 deaths) for acalabrutinib and IdR/BR, respectively. 23% of pts randomized to IdR/BR crossed over to receive subsequent acalabrutinib monotherapy. Common all-grade AEs (≥15%) with acalabrutinib were headache (22%), neutropenia (19%), diarrhea (18%), anemia and cough (15% each); with IdR, diarrhea (47%), neutropenia (45%), pyrexia (18%) and cough (15%); and with BR, neutropenia (34%), infusion-related reaction and fatigue (23% each), nausea (20%) and pyrexia (17%). Grade ≥3 AEs with acalabrutinib (≥5%) were neutropenia (16%), anemia (12%) and pneumonia (5%); with IdR (≥15%), neutropenia (40%) and diarrhea (24%); and with BR (≥5%), neutropenia (31%), anemia (9%) and constipation (6%). AEs of interest were atrial fibrillation (5.2% of pts on acalabrutinib vs 3.3% on IdR/BR), bleeding AEs (26% vs 7.2%; including major hemorrhage [1.9% vs 2.6%]), Grade ≥3 infections (15% vs 24%), and 2nd primary malignancies (excluding NMSC; 6.5% vs 2.6%). 

Conclusion

Acalabrutinib monotherapy significantly improved PFS with a more tolerable safety profile compared with IdR/BR in pts with R/R CLL.

Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical

Keyword(s): Clinical trial, Kinase inhibitor, Phase III

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