ACALABRUTINIB ± OBINUTUZUMAB VS OBINUTUZUMAB + CHLORAMBUCIL IN TREATMENT-NAÏVE CHRONIC LYMPHOCYTIC LEUKEMIA: ELEVATE-TN 4-YEAR FOLLOW-UP
Author(s): ,
Jeff Sharman
Affiliations:
Willamette Valley Cancer Institute and Research Center,Eugene,United States
,
Miklos Egyed
Affiliations:
Somogy County Mór Kaposi General Hospital,Kaposvár,Hungary
,
Wojciech Jurczak
Affiliations:
Maria Sklodowska-Curie National Research Institute of Oncology,Krakow,Poland
,
Alan Skarbnik
Affiliations:
Novant Health Cancer Institute,Charlotte,United States
,
John M. Pagel
Affiliations:
Swedish Cancer Institute,Seattle,United States
,
Ian W. Flinn
Affiliations:
Sarah Cannon Research Institute,Nashville,United States
,
Manali Kamdar
Affiliations:
University of Colorado Cancer Center,Aurora,United States
,
Munir Munir
Affiliations:
Haematology, Haematological Malignancy Diagnostic Service (HMDS), St. James’s Institute of Oncology,Leeds,United Kingdom
,
Renata Walewska
Affiliations:
Cancer Care, University Hospitals Dorset,Bournemouth,United Kingdom
,
Gillian Corbett
Affiliations:
Tauranga Hospital,Tauranga,New Zealand
,
Laura Maria Fogliatto
Affiliations:
Hospital de Clinicas de Porto Alegre,Porto Alegre,Brazil
,
Yair Herishanu
Affiliations:
Tel Aviv Sourasky Medical Center,Tel Aviv,Israel
,
Versha Banerji
Affiliations:
Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba and CancerCare Manitoba,Winnipeg,Canada
,
Steven Coutre
Affiliations:
Stanford University School of Medicine,Stanford,United States
,
George Follows
Affiliations:
Addenbrooke’s Hospital NHS Trust,Cambridge,United Kingdom
,
Patricia Walker
Affiliations:
Peninsula Health and Peninsula Private Hospital,Frankston,Australia
,
Karin Karlsson
Affiliations:
Skåne University Hospital,Lund,Sweden
,
Paolo Ghia
Affiliations:
Università Vita-Salute San Raffaele and IRCCS Ospedale, San Raffaele,Milano,Italy
,
Ann Janssens
Affiliations:
University Hospitals Leuven,Leuven,Belgium
,
Florence Cymbalista
Affiliations:
Bobigny: Hématologie, CHU Avicennes,Bobigny,France
,
Jennifer A. Woyach
Affiliations:
The Ohio State University Comprehensive Cancer Center,Columbus,United States
,
Emmanuelle Ferrant
Affiliations:
Hospices Civils de Lyon, Centre Hospitalier Lyon Sud,Lyon,France
,
William G. Wierda
Affiliations:
MD Anderson Cancer Center,Houston,United States
,
Veerendra Munugalavadla
Affiliations:
AstraZeneca,South San Francisco,United States
,
Priti Patel
Affiliations:
AstraZeneca,South San Francisco,United States
,
Min Hui Wang
Affiliations:
AstraZeneca,South San Francisco,United States
John C Byrd
Affiliations:
The Ohio State University Comprehensive Cancer Center,Columbus,United States
EHA Library. Sharman J. 06/09/21; 324556; S148
Jeff Sharman
Jeff Sharman
Contributions
Abstract
Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S148

Type: Oral Presentation

Session title: Clinical trials with targeted therapies in CLL

Background
Early results from ELEVATE-TN (NCT02475681) at a median follow-up of 28.3 months demonstrated superior efficacy of acalabrutinib (A) ± obinutuzumab (O) compared with O + chlorambucil (Clb) in patients with treatment-naïve (TN) chronic lymphocytic leukemia (CLL) (Sharman et al. Lancet 2020;395:1278-91). 

Aims
To report the updated efficacy and safety results from the ELEVATE-TN study after a median follow-up duration of 4 years. 

Methods
Patients received A±O or O+Clb. Crossover to A monotherapy was permitted in patients who progressed on O+Clb. Investigator-assessed (INV) progression-free survival (PFS), INV overall response rate (ORR), overall survival (OS), and safety were evaluated. Informed consent was obtained from all patients prior to trial enrollment.

Results
A total of 535 patients (A+O, n=179; A, n=179; O+Clb, n=177) were randomized. The median patient age was 70 years; 63% of patients had unmutated IGHV and 9% had del(17p). At a median follow-up of 46.9 months (range, 0.0–59.4; data cutoff: Sept 11, 2020), the median PFS was not reached (NR) for A+O and A patients versus 27.8 months for O+Clb patients (both P<0.0001). In patients with unmutated IGHV, the median PFS was NR (A+O and A) versus 22.2 months among O+Clb patients (both P<0.0001). In patients with del(17p), the median PFS was NR (A+O and A) versus 17.7 months for O+Clb (P<0.005). Estimated 48-month PFS rates were 87% for A+O, 78% for A, and 25% for O+Clb. Median OS was NR in any treatment arm with a trend towards significance in the A+O group (A+O vs O+Clb, P=0.0604); estimated 48-month OS rates were 93% (A+O), 88% (A), and 88% (O+Clb). ORR was significantly higher with A+O (96.1%; 95% CI 92.1–98.1) versus O+Clb (82.5%; 95% CI 76.2–87.4; P<0.0001); ORR with A was 89.9% (95% CI 84.7–93.5; P=0.035 vs O+Clb). Complete response/complete response with incomplete hematologic recovery (CR/CRi) rates were higher with A+O (26.8%/3.9%) versus O+Clb (12.4%/0.6%); 10.6%/0.6% had CR/CRi with A. Common adverse events (AEs) and AEs of interest are shown in the Table. Overall treatment discontinuation rates were 25.1% (A+O), 30.7% (A), and 22.6% (O+Clb); the most common reasons were AEs (12.8%, 12.3%, 14.7%, respectively) and progressive disease (4.5%, 7.8%, 1.7%). Most patients (77.4%) completed O+Clb treatment. 

Conclusion
With a median follow-up of 46.9 months (~4 years) in the ELEVATE-TN study, the efficacy and safety of A+O and A monotherapy was maintained, with an increase in CR since the interim analysis (from 21% to 27% [A+O] and from 7% to 11% [A]) and low rates of discontinuation.

Keyword(s): Chronic lymphocytic leukemia, Phase III

Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S148

Type: Oral Presentation

Session title: Clinical trials with targeted therapies in CLL

Background
Early results from ELEVATE-TN (NCT02475681) at a median follow-up of 28.3 months demonstrated superior efficacy of acalabrutinib (A) ± obinutuzumab (O) compared with O + chlorambucil (Clb) in patients with treatment-naïve (TN) chronic lymphocytic leukemia (CLL) (Sharman et al. Lancet 2020;395:1278-91). 

Aims
To report the updated efficacy and safety results from the ELEVATE-TN study after a median follow-up duration of 4 years. 

Methods
Patients received A±O or O+Clb. Crossover to A monotherapy was permitted in patients who progressed on O+Clb. Investigator-assessed (INV) progression-free survival (PFS), INV overall response rate (ORR), overall survival (OS), and safety were evaluated. Informed consent was obtained from all patients prior to trial enrollment.

Results
A total of 535 patients (A+O, n=179; A, n=179; O+Clb, n=177) were randomized. The median patient age was 70 years; 63% of patients had unmutated IGHV and 9% had del(17p). At a median follow-up of 46.9 months (range, 0.0–59.4; data cutoff: Sept 11, 2020), the median PFS was not reached (NR) for A+O and A patients versus 27.8 months for O+Clb patients (both P<0.0001). In patients with unmutated IGHV, the median PFS was NR (A+O and A) versus 22.2 months among O+Clb patients (both P<0.0001). In patients with del(17p), the median PFS was NR (A+O and A) versus 17.7 months for O+Clb (P<0.005). Estimated 48-month PFS rates were 87% for A+O, 78% for A, and 25% for O+Clb. Median OS was NR in any treatment arm with a trend towards significance in the A+O group (A+O vs O+Clb, P=0.0604); estimated 48-month OS rates were 93% (A+O), 88% (A), and 88% (O+Clb). ORR was significantly higher with A+O (96.1%; 95% CI 92.1–98.1) versus O+Clb (82.5%; 95% CI 76.2–87.4; P<0.0001); ORR with A was 89.9% (95% CI 84.7–93.5; P=0.035 vs O+Clb). Complete response/complete response with incomplete hematologic recovery (CR/CRi) rates were higher with A+O (26.8%/3.9%) versus O+Clb (12.4%/0.6%); 10.6%/0.6% had CR/CRi with A. Common adverse events (AEs) and AEs of interest are shown in the Table. Overall treatment discontinuation rates were 25.1% (A+O), 30.7% (A), and 22.6% (O+Clb); the most common reasons were AEs (12.8%, 12.3%, 14.7%, respectively) and progressive disease (4.5%, 7.8%, 1.7%). Most patients (77.4%) completed O+Clb treatment. 

Conclusion
With a median follow-up of 46.9 months (~4 years) in the ELEVATE-TN study, the efficacy and safety of A+O and A monotherapy was maintained, with an increase in CR since the interim analysis (from 21% to 27% [A+O] and from 7% to 11% [A]) and low rates of discontinuation.

Keyword(s): Chronic lymphocytic leukemia, Phase III

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