@article{20d990710ea74d9088751148e5d04763,
title = "A phase 2, multicentre, open-label trial (ACE-LY-003) of acalabrutinib in patients with relapsed or refractory marginal zone lymphoma",
abstract = "Acalabrutinib, a Bruton tyrosine kinase inhibitor, demonstrated greater selectivity and improved safety versus ibrutinib in a head-to-head trial in relapsed/refractory (R/R) chronic lymphocytic leukaemia. In the R/R marginal zone lymphoma (MZL) cohort (phase 2) of a phase 1b/2 trial (NCT02180711), 43 patients with MZL and at least one prior therapy received acalabrutinib 100 mg twice daily until disease progression or unacceptable toxicity [median age 69 years (range 42–84); median one (1–4) prior systemic regimens]. Median follow-up was 13.3 months (range 0.5–45.5). Among 40 patients evaluable for response, investigator-assessed overall response rate was 53% [95% confidence interval (CI) 36%–69%] with five (13%) complete responses. Tumour reduction occurred in 40 (93%) of the treated patients. Median time to response was 2.9 months (median duration of response not estimable). Estimated median progression-free survival (PFS) was 27.4 months (12-month PFS rate, 67%). Five patients died (disease progression, n = 4; septic shock, n = 1). Seventeen patients (40%) had grade 3 or higher adverse events (AEs), most commonly neutropenia (14%), anaemia, dyspnoea (7% each), fatigue and thrombocytopenia (5% each). Hypertension occurred in 5%; atrial fibrillation/flutter and major haemorrhage were not reported. AEs led to treatment discontinuation in three (7%) patients. Acalabrutinib was active and well tolerated in patients with R/R MZL.",
keywords = "B-cell lymphoma, Bruton tyrosine kinase, non-Hodgkin lymphoma",
author = "Paolo Strati and Morton Coleman and Rebecca Champion and Shuo Ma and Caterina Patti and Levy, {Moshe Y.} and Lossos, {Izidore S.} and Geethakumari, {Praveen Ramakrishnan} and Selay Lam and Roser Calvo and Kara Higgins and Budde, {Lihua E.}",
note = "Funding Information: Paolo Strati has consulted and served on an advisory board for Roche‐Genentech, ADC Therapeutics, TG Therapeutics and Hutchinson‐MediPharma, and has received research support from AstraZeneca, Acerta and ALX Oncology. Morton Coleman has served on advisory boards and received research support from AbbVie, AstraZeneca, BeiGene, Loxo Oncology, Janssen Pharmaceuticals, Pharmacyclics, Bristol Meyers Squibb and Gilead Sciences. Rebecca Champion has served on the speakers' bureau for Bristol Myers Squibb and AbbVie and has received honoraria for advisory boards for BeiGene. Shuo Ma has received research grants from AbbVie, AstraZeneca, BeiGene, Janssen, Juno, Loxo, Pharmacyclics and TG Therapeutics; received honoraria for advisory board or consulting from AbbVie, AstraZeneca, BeiGene, Genentech, Janssen, Pharmacyclics and TG Therapeutics, and served on speakers' bureaus for AstraZeneca, BeiGene, Janssen and Pharmacyclics. Caterina Patti has received honoraria for advisory board or consulting from AbbVie, AstraZeneca, Janssen and Takeda. Moshe Y. Levy has served as a consultant/promotional speaker for AbbVie, Amgen Inc., Bristol Myers Squibb, Janssen Pharmaceuticals, Karyopharm, Morphosys, Seattle Genetics, Takeda, AstraZeneca, BeiGene, Gilead Sciences, Jazz Pharmaceuticals, TG Therapeutics, Epizyme, GSK, Novartis and Dova. Izidore S. Lossos has served on advisory boards for Seattle Genetics, Janssen Scientific, Adaptive Biotechnologies, Verastem and Pharmacyclics. Praveen Ramakrishnan Geethakumari has provided consultancy for Kite Pharma, Pharmacyclics and Rafael Pharmaceuticals. Selay Lam has received honoraria from AbbVie, Amgen, AstraZeneca, BeiGene, BMS, Gilead Sciences, Roche, Janssen, Novartis, Sanofi and Seattle Genetics, and has served in a consulting or advisory role for AbbVie, Amgen, AstraZeneca, BeiGene, BMS, Gilead Sciences, Roche, Janssen, Novartis, Sanofi and Seattle Genetics. Rebecca Champion is a paid employee of AstraZeneca and reports stock ownership in the company. Kara Higgins is a paid employee of AstraZeneca. Lihua E. Budde has served on advisory boards for Genentech/Roche, ADC Therapeutics, BeiGene and Gilead Sciences and has received research grants from Mustang Therapeutics, Merck, Amgen and AstraZeneca. Funding Information: The authors would like to thank the investigators, study/site/data coordinators, regulatory personnel, patients who participated in the current study and their families and Robin Lesley, PhD, of AstraZeneca, for data analysis support. The study was funded by AstraZeneca. Medical writing assistance, funded by AstraZeneca, was provided by Robert J. Schoen, PharmD, of Peloton Advantage, LLC, an OPEN Health company, under the direction of the authors. Publisher Copyright: {\textcopyright} 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.",
year = "2022",
month = oct,
doi = "10.1111/bjh.18368",
language = "English (US)",
volume = "199",
pages = "76--85",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "1",
}