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

Michael Wang 1, * Simon Rule 2 Pier Luigi Zinzani 3 Andre Goy 4 Olivier Casasnovas 5, 6 Stephen Smith 7 Gandhi Damaj 8 Jeanette Doorduijn 9 Thierry Lamy 10 Franck Morschhauser 11 Carlos Panizo 12 Bijal Shah 13 Andrew Davies 14 Richard Eek Jehan Dupuis 15 Eric Jacobsen Arnon Kater Steven Le Gouill 16, 17 Lucie Oberic 18 Taduesz Robak 19 Todd Covey 20 Richa Dua 20 Ahmed Hamdy 20 Xin Huang 20 Raquel Izumi 20 Priti Patel 20 Wayne Rothbaum 19 J Greg Slatter 20 Wojciech Jurczak 21
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, 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. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Contributeur : Lnc - Université de Bourgogne <>
Soumis le : jeudi 8 mars 2018 - 09:32:51
Dernière modification le : mercredi 19 août 2020 - 11:17:38



Michael Wang, Simon Rule, Pier Luigi Zinzani, Andre Goy, Olivier Casasnovas, et al.. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. The Lancet, Elsevier, 2018, 391 (10121), pp.659 - 667. ⟨10.1016/S0140-6736(17)33108-2⟩. ⟨hal-01726196⟩



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