ACALABRUTINIB IN TREATMENT-NAÏVE CHRONIC LYMPHOCYTIC LEUKEMIA: MATURE RESULTS FROM PHASE 2 STUDY DEMONSTRATING DURABLE REMISSIONS AND LONG-TERM TOLERABILITY
Author(s): ,
John C. Byrd
Affiliations:
The Ohio State University Comprehensive Cancer Center,Columbus,United States
,
Jennifer A. Woyach
Affiliations:
The Ohio State University Comprehensive Cancer Center,Columbus,United States
,
Richard R. Furman
Affiliations:
Weill Cornell Medicine, New York Presbyterian Hospital,New York,United States
,
Peter Martin
Affiliations:
Weill Cornell Medicine, New York Presbyterian Hospital,New York,United States
,
Susan M. O'Brien
Affiliations:
Chao Family Comprehensive Cancer Center, University of California,Irvine,United States
,
Jennifer R. Brown
Affiliations:
Dana-Farber Cancer Institute,Boston,United States
,
Deborah M. Stephens
Affiliations:
University of Utah Huntsman Cancer Institute,Salt Lake City,United States
,
Jacqueline C. Barrientos
Affiliations:
Zucker School of Medicine at Hofstra/Northwell,Hempstead,United States
,
Stephen Devereux
Affiliations:
College Hospital, NHS Foundation Trust Denmark Hill,London,United Kingdom
,
Peter Hillmen
Affiliations:
St James's University Hospital,Leeds,United Kingdom
,
John M. Pagel
Affiliations:
Swedish Cancer Institute ,Seattle,United States
,
Ahmed M. Hamdy
Affiliations:
Acerta Pharma ,South San Francisco,United States
,
Raquel Izumi
Affiliations:
Acerta Pharma,South San Francisco,United States
,
Priti Patel
Affiliations:
Acerta Pharma,South San Francisco,United States
,
Min Hui Wang
Affiliations:
Acerta Pharma,South San Francisco,United States
,
Nitin Jain
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
William G. Wierda
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
EHA Library. C. Byrd J. 06/12/20; 294983; S163
John C. Byrd
John C. Byrd
Contributions
Abstract

Abstract: S163

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 II

Background
The next-generation Bruton tyrosine kinase inhibitor acalabrutinib was approved in patients with treatment-naïve (TN) and relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) based on two complementary phase 3 studies, ELEVATE-TN and ASCEND.  

Aims
This report of ACE-CL-001 (NCT02029443), the first phase 2 study of acalabrutinib, provides the longest safety and efficacy follow-up to date in symptomatic patients with TN CLL.

Methods
Adults with TN CLL/SLL were eligible if they met International Workshop on Chronic Lymphocytic Leukemia 2008 criteria for treatment, were inappropriate for/declined standard chemotherapy, and had Eastern Cooperative Oncology Group performance status 0–2. Patients received acalabrutinib 100 mg twice daily (BID) or 200 mg once daily (QD), later switching to 100 mg BID, until progressive disease (PD) or unacceptable toxicity. Primary endpoint was safety. Events of clinical interest (ECI) were based on combined adverse event (AE) terms for infections, bleeding events, hypertension, and second primary malignancies (SPM) excluding non-melanoma skin and on a single AE term for atrial fibrillation. Additional endpoints included investigator-assessed overall response rate (ORR), duration of response (DOR), time to response (TTR), and event-free survival (EFS). All patients provided informed consent.

Results
Ninety-nine patients (n=62 100 mg BID; n=37 200 mg QD), were treated [median age: 64 years, 47% Rai stage 3–4 disease, 10% del(17p), 62% unmutated immunoglobulin heavy chain variable region (IGHV)]. At median follow-up of 53 months (range, 1–59), 85 (86%) patients remain on treatment; most discontinuations were due to AEs (n=6) or PD (n=3 [n=1 Richter transformation]). Most common AEs (any grade) were diarrhea (52%), headache (45%), upper respiratory tract infection (44%), arthralgia (42%), and contusion (42%). All-grade and grade ≥3 ECIs included infection (84%, 15%), bleeding events (66%, 3%), and hypertension (22%, 11%). Atrial fibrillation (all grades) occurred in 5% of patients (incidence: 1% in years 1, 2, 4; 3% in year 3). SPMs excluding non-melanoma skin (all grades) occurred in 11%. Serious AEs were reported in 38% of patients; those in >2 patients were pneumonia (n=4) and sepsis (n=3). ORR was 97% (7% complete response; 90% partial response). Median TTR was 3.7 months (range, 2–22). Response rates were similar across high-risk groups. Median DOR and median EFS were not reached; 48-month DOR rate was 97% (95% confidence interval [CI], 90%–99%), and 48-month EFS rate was 90% (95% CI, 82%–94%).

Conclusion
Long-term data from ACE-CL-001 in patients with TN CLL/SLL further support the favorable results with acalabrutinib in phase 3 studies and demonstrate durable responses with no new long-term safety issues.

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

Keyword(s): Chronic lymphocytic leukemia, Phase II

Abstract: S163

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 II

Background
The next-generation Bruton tyrosine kinase inhibitor acalabrutinib was approved in patients with treatment-naïve (TN) and relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) based on two complementary phase 3 studies, ELEVATE-TN and ASCEND.  

Aims
This report of ACE-CL-001 (NCT02029443), the first phase 2 study of acalabrutinib, provides the longest safety and efficacy follow-up to date in symptomatic patients with TN CLL.

Methods
Adults with TN CLL/SLL were eligible if they met International Workshop on Chronic Lymphocytic Leukemia 2008 criteria for treatment, were inappropriate for/declined standard chemotherapy, and had Eastern Cooperative Oncology Group performance status 0–2. Patients received acalabrutinib 100 mg twice daily (BID) or 200 mg once daily (QD), later switching to 100 mg BID, until progressive disease (PD) or unacceptable toxicity. Primary endpoint was safety. Events of clinical interest (ECI) were based on combined adverse event (AE) terms for infections, bleeding events, hypertension, and second primary malignancies (SPM) excluding non-melanoma skin and on a single AE term for atrial fibrillation. Additional endpoints included investigator-assessed overall response rate (ORR), duration of response (DOR), time to response (TTR), and event-free survival (EFS). All patients provided informed consent.

Results
Ninety-nine patients (n=62 100 mg BID; n=37 200 mg QD), were treated [median age: 64 years, 47% Rai stage 3–4 disease, 10% del(17p), 62% unmutated immunoglobulin heavy chain variable region (IGHV)]. At median follow-up of 53 months (range, 1–59), 85 (86%) patients remain on treatment; most discontinuations were due to AEs (n=6) or PD (n=3 [n=1 Richter transformation]). Most common AEs (any grade) were diarrhea (52%), headache (45%), upper respiratory tract infection (44%), arthralgia (42%), and contusion (42%). All-grade and grade ≥3 ECIs included infection (84%, 15%), bleeding events (66%, 3%), and hypertension (22%, 11%). Atrial fibrillation (all grades) occurred in 5% of patients (incidence: 1% in years 1, 2, 4; 3% in year 3). SPMs excluding non-melanoma skin (all grades) occurred in 11%. Serious AEs were reported in 38% of patients; those in >2 patients were pneumonia (n=4) and sepsis (n=3). ORR was 97% (7% complete response; 90% partial response). Median TTR was 3.7 months (range, 2–22). Response rates were similar across high-risk groups. Median DOR and median EFS were not reached; 48-month DOR rate was 97% (95% confidence interval [CI], 90%–99%), and 48-month EFS rate was 90% (95% CI, 82%–94%).

Conclusion
Long-term data from ACE-CL-001 in patients with TN CLL/SLL further support the favorable results with acalabrutinib in phase 3 studies and demonstrate durable responses with no new long-term safety issues.

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

Keyword(s): Chronic lymphocytic leukemia, Phase II

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