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

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

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.

Journal Article
0140-6736
659-667
Wang, Michael
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Rule, Simon
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Zinzani, Pier Luigi
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Goy, Andre
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Casasnovas, Olivier
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Smith, Stephen D.
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Damaj, Gandhi
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Doorduijn, Jeanette
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Lamy, Thierry
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Morschhauser, Franck
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Panizo, Carlos
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Shah, Bijal
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Davies, Andrew
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Eek, Richard
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Dupuis, Jehan
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Jacobsen, Eric
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Kater, Arnon P.
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Le Gouill, Steven
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Oberic, Lucie
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Robak, Taduesz
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Covey, Todd
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Dua, Richa
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Hamdy, Ahmed
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Huang, Xin
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Izumi, Raquel
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Patel, Priti
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Rothbaum, Wayne
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Slatter, J. Greg
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Jurczak, Wojciech
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Wang, Michael
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Rule, Simon
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Zinzani, Pier Luigi
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Goy, Andre
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Casasnovas, Olivier
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Smith, Stephen D.
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Damaj, Gandhi
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Doorduijn, Jeanette
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Lamy, Thierry
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Morschhauser, Franck
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Panizo, Carlos
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Shah, Bijal
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Davies, Andrew
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Eek, Richard
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Dupuis, Jehan
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Jacobsen, Eric
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Kater, Arnon P.
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Le Gouill, Steven
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Oberic, Lucie
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Robak, Taduesz
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Covey, Todd
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Dua, Richa
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Hamdy, Ahmed
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Huang, Xin
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Izumi, Raquel
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Patel, Priti
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Rothbaum, Wayne
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Slatter, J. Greg
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Jurczak, Wojciech
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Wang, Michael, Rule, Simon, Zinzani, Pier Luigi, Goy, Andre, Casasnovas, Olivier, Smith, Stephen D., Damaj, Gandhi, Doorduijn, Jeanette, Lamy, Thierry, Morschhauser, Franck, Panizo, Carlos, Shah, Bijal, Davies, Andrew, Eek, Richard, Dupuis, Jehan, Jacobsen, Eric, Kater, Arnon P., Le Gouill, Steven, Oberic, Lucie, Robak, Taduesz, Covey, Todd, Dua, Richa, Hamdy, Ahmed, Huang, Xin, Izumi, Raquel, Patel, Priti, Rothbaum, Wayne, Slatter, J. Greg and Jurczak, Wojciech (2018) Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. The Lancet, 391 (10121), 659-667. (doi:10.1016/S0140-6736(17)33108-2).

Record type: Article

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.

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More information

Accepted/In Press date: 24 November 2017
e-pub ahead of print date: 11 December 2017
Published date: 17 February 2018
Keywords: Journal Article

Identifiers

Local EPrints ID: 418616
URI: http://eprints.soton.ac.uk/id/eprint/418616
ISSN: 0140-6736
PURE UUID: e6a512d2-6b34-4fbc-8cbe-ded6c026a925
ORCID for Andrew Davies: ORCID iD orcid.org/0000-0002-7517-6938

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Date deposited: 12 Mar 2018 17:31
Last modified: 16 Aug 2024 01:42

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Contributors

Author: Michael Wang
Author: Simon Rule
Author: Pier Luigi Zinzani
Author: Andre Goy
Author: Olivier Casasnovas
Author: Stephen D. Smith
Author: Gandhi Damaj
Author: Jeanette Doorduijn
Author: Thierry Lamy
Author: Franck Morschhauser
Author: Carlos Panizo
Author: Bijal Shah
Author: Andrew Davies ORCID iD
Author: Richard Eek
Author: Jehan Dupuis
Author: Eric Jacobsen
Author: Arnon P. Kater
Author: Steven Le Gouill
Author: Lucie Oberic
Author: Taduesz Robak
Author: Todd Covey
Author: Richa Dua
Author: Ahmed Hamdy
Author: Xin Huang
Author: Raquel Izumi
Author: Priti Patel
Author: Wayne Rothbaum
Author: J. Greg Slatter
Author: Wojciech Jurczak

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