TY - JOUR
T1 - Acalabrutinib in treatment-naive chronic lymphocytic leukemia
AU - Byrd, John C.
AU - Woyach, Jennifer A.
AU - Furman, Richard R.
AU - Martin, Peter
AU - O'Brien, Susan
AU - Brown, Jennifer R.
AU - Stephens, Deborah M.
AU - Barrientos, Jacqueline C.
AU - Devereux, Stephen
AU - Hillmen, Peter
AU - Pagel, John M.
AU - Hamdy, Ahmed
AU - Izumi, Raquel
AU - Patel, Priti
AU - Wang, Min Hui
AU - Jain, Nitin
AU - Wierda, William G.
N1 - Funding Information:
The authors thank the patients who participated in this study and their families, the investigators, and coordinators at each of the clinical sites. Medical writing assistance, funded by Acerta Pharma, was provided by Tracy Diaz and Cindy Gobbel of Peloton Advantage, LLC, an OPEN Health company, under the direction of the authors.
Funding Information:
The authors thank the patients who participated in this study and their families, the investigators, and coordinators at each of the clinical sites. Medical writing assistance, funded by Acerta Pharma, was provided by Tracy Diaz and Cindy Gobbel of Peloton Advantage, LLC, an OPEN Health company, under the direction of the authors. This project was supported National Institutes of Health, National Cancer Institute grant R35 CA197734 (J.C. Byrd), The Connie Brown CLL Foundation, the Kevin Sullivan Foundation, the D. Warren Brown Foundation, and the Four Winds Foundation. This study was funded by Acerta Pharma (South San Francisco, CA), a member of the AstraZeneca Group. Acerta Pharma provided the study drug. The clinical study was designed by A.H. and R.I. (Acerta Pharma) in collaboration with J.C. Byrd (The Ohio State University Comprehensive Cancer Center, Columbus, OH). Data collection and interpretation were performed by the authors, investigators, and study sponsor. The study sponsor reviewed the manuscript for accuracy.
Funding Information:
This project was supported National Institutes of Health, National Cancer Institute grant R35 CA197734 (J.C. Byrd), The Connie Brown CLL Foundation, the Kevin Sullivan Foundation, the D. Warren Brown Foundation, and the Four Winds Foundation.
Funding Information:
Conflict-of-interest disclosure: J. C. Byrd has received research funding from Janssen, Genentech, Pharmacyclics, and Acerta. J.A.W. served in a consulting or advisory role for AbbVie, Pharmacyclics, Janssen, AstraZeneca, ArQule; and has received research funding from Janssen, Karyopharm Therapeutics, MorphoSys, Verastem, Loxo, AbbVie. R.R.F. served in a consulting or advisory role for Pharmacyclics, Janssen Biotech, Genentech/Roche, Sunesis Pharmaceuticals, Loxo, TG Therapeutics, Verastem, Acerta Pharma, AstraZeneca, BeiGene, Incyte, OncoTracker, AbbVie; and has received fees for travel, accommodations, expenses from TG Therapeutics, Janssen Oncology; provided expert testimony for AbbVie, Janssen Oncology; maintains other relationships with Incyte, Janssen Biotech, AbbVie; has received honoraria from Janssen, Genentech/Roche; and has received research funding from Acerta Pharma, TG Therapeutics. P.M. served in a consulting or advisory role for AstraZeneca, Celgene, Janssen, Bayer, Kite Pharma, BeiGene, Celldex, Cellectar, I-Mab, MorphoSys, Regeneron, Sandoz, TeneoBio, Verastem, Karyopharm Therapeutics; has received fees for travel, accommodations, expenses from Janssen, MorphoSys; and has received research funding (the Institution) from Karyopharm Therapeutics. S.O. is employed by University of California Irvine; served in a consulting or advisory role for Amgen, Celgene, GlaxoSmithKline, Janssen Oncology, Aptose Biosciences, Vaniam Group, AbbVie/Genentech, Sunesis Pharmaceuticals, Alexion Pharmaceuticals, Astellas Pharma, Gilead Sciences, Pharmacyclics, TG Therapeutics, Pfizer, Verastem, Eisai, Juno Therapeutics, Vida Ventures; has received fees for travel, accommodations, expenses from Celgene, Janssen, Gilead Sciences, Regeneron, Janssen Oncology; has received honoraria from Celgene, Janssen, Pharmacyclics, Gilead Sciences, Pfizer, Amgen, Astellas Pharma, GlaxoSmithKline, Aptose Biosciences, Vaniam Group, AbbVie, Sunesis Pharmaceuticals, Alexion Pharmaceuticals, Loxo, Eisai, TG Therapeutics; has received research funding (the Institution) from Acerta Pharma, Regeneron, Gilead Sciences, Pfizer, TG Therapeutics, Pharmacyclics, Kite Pharma, Sunesis Pharmaceuticals. J.R.B. served in a consulting or advisory role for AbbVie, Acerta, AstraZeneca, BeiGene, Catapult, Dynamo, Eli Lilly, Genentech/Roche, Gilead, Juno/Celgene, Kite, Loxo, MEI Pharma, Nextcea, Novartis, Octapharma, Rigel, Pfizer, Pharmacyclics, Redx, Sun, Sunesis, TG Therapeutics, Verastem; has received honoraria from Janssen and Teva; has received research funding from Gilead, Loxo, Sun, Verastem; and has served on data safety monitoring committees for Morphosys, Invectys. D.M.S. served in a consulting or advisory role for Pharmacyclics/Janssen, Karyopharm, BeiGene, Innate; has received honoraria from Genentech; has received research funding from Acerta Pharma, Gilead Sciences, Karyopharm Therapeutics, Verastem, Juno Therapeutics. J. C. Barrientos served in a consulting or advisory role for Pharmacyclics, AbbVie, AstraZeneca, Gilead Sciences, Genentech, Bayer, Sandoz; has received fees for travel, accommodations, expenses from Janssen; has received honoraria from Janssen; has received research funding (the Institution) from Pharmacyclics, Oncternal Therapeutics, AstraZeneca. P.H. has received fees for travel, accommodations, expenses from Janssen, AbbVie; has received honoraria from Janssen, AbbVie, Roche; has received research funding (the Institution) from Janssen, Pharmacyclics, Roche, Gilead Sciences. J.M.P. served in a consulting or advisory role for Pharmacyclics, Gilead Sciences, AstraZeneca, Actinium Pharmaceuticals. A.H. and R.I. hold stock ownership/patents for Acerta Pharma and are former employees of Acerta at the time of the study. P.P. and M.H.W. are employed or hold stock ownership in Acerta Pharma/AstraZeneca. N.J. served in a consulting or advisory role for Pharmacyclics, Janssen, AbbVie, Genentech, AstraZeneca, Verastem, Adaptive Biotechnologies, Servier, Precision Biosciences, TG Therapeutics, BeiGene; has received research funding (the Institution) from Pharmacyclics, AbbVie, Genentech, AstraZeneca, Bristol Myers Squibb, Pfizer, ADC Therapeutics, Incyte, Servier, Cellectis, Verastem, Adaptive Biotechnologies, Precision Biosciences, Fate Therapeutics, Aprea Therapeutics. W.G.W. served in a consulting or advisory role for Sanofi; has received research funding from GlaxoSmithKline/Novartis, AbbVie, Genentech, Karyopharm Therapeutics, Pharmacyclics, Acerta Pharma, Gilead Sciences, Janssen, Emergent BioSolutions, Juno Therapeutics, Kite Pharma, Oncternal Therapeutics, Inc, Loxo, Xencor, miRagen, Sunesis Pharmaceuticals, Cyclacel. S.D. declares no competing financial interests.
Publisher Copyright:
© 2021 American Society of Hematology
PY - 2021/6/17
Y1 - 2021/6/17
N2 - Acalabrutinib has demonstrated significant efficacy and safety in relapsed chronic lymphocytic leukemia (CLL). Efficacy and safety of acalabrutinib monotherapy were evaluated in a treatment-naive CLL cohort of a single-arm phase 1/2 trial (ACE-CL-001). Adults were eligible for enrollment if chemotherapy was declined or deemed inappropriate due to comorbidities (N = 99). Patients had a median age of 64 years and 47% had Rai stage III/IV disease. Acalabrutinib was administered orally 200 mg once daily, or 100 mg twice daily until progression or intolerance. A total of 99 patients were treated; 57 (62%) had unmutated immunoglobulin heavy-chain variable gene, and 12 (18%) had TP53 aberrations. After median follow-up of 53 months, 85 patients remain on treatment; 14 discontinued treatment, mostly because of adverse events (AEs) (n = 6) or disease progression (n = 3). Overall response rate was 97% (90% partial response; 7% complete response), with similar outcomes among all prognostic subgroups. Because of improved trough BTK occupancy with twice-daily dosing, all patients were transitioned to 100 mg twice daily. Median duration of response (DOR) was not reached; 48-month DOR rate was 97% (95% confidence interval, 90-99). Serious AEs were reported in 38 patients (38%). AEs required discontinuation in 6 patients (6%) because of second primary cancers (n = 4) and infection (n = 2). Grade ≥3 events of special interest included infection (15%), hypertension (11%), bleeding events (3%), and atrial fibrillation (2%). Durable efficacy and long-term safety of acalabrutinib in this trial support its use in clinical management of symptomatic, untreated patients with CLL.
AB - Acalabrutinib has demonstrated significant efficacy and safety in relapsed chronic lymphocytic leukemia (CLL). Efficacy and safety of acalabrutinib monotherapy were evaluated in a treatment-naive CLL cohort of a single-arm phase 1/2 trial (ACE-CL-001). Adults were eligible for enrollment if chemotherapy was declined or deemed inappropriate due to comorbidities (N = 99). Patients had a median age of 64 years and 47% had Rai stage III/IV disease. Acalabrutinib was administered orally 200 mg once daily, or 100 mg twice daily until progression or intolerance. A total of 99 patients were treated; 57 (62%) had unmutated immunoglobulin heavy-chain variable gene, and 12 (18%) had TP53 aberrations. After median follow-up of 53 months, 85 patients remain on treatment; 14 discontinued treatment, mostly because of adverse events (AEs) (n = 6) or disease progression (n = 3). Overall response rate was 97% (90% partial response; 7% complete response), with similar outcomes among all prognostic subgroups. Because of improved trough BTK occupancy with twice-daily dosing, all patients were transitioned to 100 mg twice daily. Median duration of response (DOR) was not reached; 48-month DOR rate was 97% (95% confidence interval, 90-99). Serious AEs were reported in 38 patients (38%). AEs required discontinuation in 6 patients (6%) because of second primary cancers (n = 4) and infection (n = 2). Grade ≥3 events of special interest included infection (15%), hypertension (11%), bleeding events (3%), and atrial fibrillation (2%). Durable efficacy and long-term safety of acalabrutinib in this trial support its use in clinical management of symptomatic, untreated patients with CLL.
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U2 - 10.1182/blood.2020009617
DO - 10.1182/blood.2020009617
M3 - Article
C2 - 33786588
AN - SCOPUS:85108258205
SN - 0006-4971
VL - 137
SP - 3327
EP - 3338
JO - Blood
JF - Blood
IS - 24
ER -