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Lancet. 2018 Feb 17;391(10121):659-667. doi: 10.1016/S0140-6736(17)33108-2. Epub 2017 Dec 11.

Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial.

Author information

1
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: miwang@mdanderson.org.
2
Plymouth University Medical School, Plymouth, UK.
3
Institute of Hematology Seràgnoli, University of Bologna, Bologna, Italy.
4
John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA.
5
Department of Hematology, Centre Hospitalier Universitaire (CHU) de Dijon, INSERM UMR 1231, Dijon, France.
6
Fred Hutchinson Cancer Research Center, University of Washington Seattle, WA, USA.
7
Institut d'Hématologie de Basse-Normandie, Caen, France.
8
Erasmus Medical Centre, Rotterdam, The Netherlands; HOVON Lunenburg Lymphoma Phase I/II Consortium, Netherlands.
9
CHU de Rennes, Rennes, France.
10
Univeristé Lille, CHU Lille, EA 7365, Groupe de Recherche sur les formes Injectables et les Technologies Associées, Lille, France.
11
Clínica Universidad de Navarra, Pamplona, Spain.
12
H Lee Moffitt Cancer Center, Tampa, FL, USA.
13
Cancer Research UK Centre, Cancer Sciences Unit, University of Southampton, Southampton, UK; Faculty of Medicine, Southampton General Hospital, Southampton, UK.
14
Border Medical Oncology, Wodonga, VIC, Australia.
15
Unité Hémopathies Lymphoïdes, Assistance Publique Hôpitaux de Paris, Hôpital Henri Mondor, Créteil, France.
16
Dana Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
17
HOVON Lunenburg Lymphoma Phase I/II Consortium, Netherlands; Academic Medical Center, Amsterdam, Netherlands.
18
CHU de Nantes, Hotel Dieu, Nantes, France; INSERM UMR 892 Team 10, Nantes, France.
19
Institut Universitaire du Cancer, Oncopole Toulouse (IUCT-O), Toulouse, France.
20
Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland.
21
Acerta Pharma, Redwood City, CA, USA.
22
Department of Hematology, Jagiellonian University, Krakow, Poland.

Abstract

BACKGROUND:

Bruton tyrosine kinase is a clinically validated target in mantle cell lymphoma. Acalabrutinib (ACP-196) is a highly selective, potent Bruton tyrosine kinase inhibitor developed to minimise off-target activity.

METHODS:

In this open-label, phase 2 study, oral acalabrutinib (100 mg twice per day) was given to patients with relapsed or refractory mantle cell lymphoma, until disease progression or unacceptable toxicity. The primary endpoint was overall response assessed according to the Lugano classification, and safety analyses were done in all participants. This trial is registered with ClinicalTrials.gov, number NCT02213926.

FINDINGS:

From March 12, 2015, to Jan 5, 2016, 124 patients with relapsed or refractory mantle cell lymphoma were enrolled and all patients received treatment; median age 68 years. Patients received a median of two (IQR 1-2) previous therapies. At a median follow-up of 15·2 months, 100 (81%) patients achieved an overall response and 49 (40%) patients achieved a complete response. The Kaplan-Meier estimated medians for duration of response, progression-free survival, and overall survival were not reached; the 12-month rates were 72% (95% CI 62-80), 67% (58-75), and 87% (79-92%), respectively. The most common adverse events were primarily grade 1 or 2 and were headache (47 [38%]), diarrhoea (38 [31%]), fatigue (34 [27%]), and myalgia (26 [21%]). The most common grade 3 or worse adverse events were neutropenia (13 [10%]), anaemia (11 [9%]), and pneumonia (six [5%]). There were no cases of atrial fibrillation and one case of grade 3 or worse haemorrhage. The median duration of treatment was 13·8 months. Treatment was discontinued in 54 (44%) patients, primarily due to progressive disease (39 [31%]) and adverse events (seven [6%]).

INTERPRETATION:

Acalabrutinib treatment provided a high rate of durable responses and a favourable safety profile in patients with relapsed or refractory mantle cell lymphoma. These findings suggest an important role for acalabrutinib in the treatment of this disease population.

FUNDING:

Acerta Pharma, a member of the AstraZeneca Group.

PMID:
29241979
DOI:
10.1016/S0140-6736(17)33108-2
[Indexed for MEDLINE]

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