Michael Wang1, Simon Rule2, Pier Luigi Zinzani3, Andre Goy4, Olivier Casasnovas5, Stephen D Smith6, Gandhi Damaj7, Jeanette Doorduijn8, Thierry Lamy9, Franck Morschhauser10, Carlos Panizo11, Bijal Shah12, Andrew Davies13, Richard Eek14, Jehan Dupuis15, Eric Jacobsen16, Arnon P Kater17, Steven Le Gouill18, Lucie Oberic19, Taduesz Robak20, Todd Covey21, Richa Dua21, Ahmed Hamdy21, Xin Huang21, Raquel Izumi21, Priti Patel21, Wayne Rothbaum21, J Greg Slatter21, Wojciech Jurczak22. 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.
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.
Authors: Julio Delgado; Filip Josephson; Jorge Camarero; Blanca Garcia-Ochoa; Lucia Lopez-Anglada; Carolina Prieto-Fernandez; Paula B van Hennik; Irene Papadouli; Christian Gisselbrecht; Harald Enzmann; Francesco Pignatti Journal: Oncologist Date: 2021-02-10
Authors: Peter Martin; Nancy L Bartlett; Kristie A Blum; Steven Park; Kami Maddocks; Jia Ruan; LeAnn Ridling; Christopher Dittus; Zhengming Chen; Xiangao Huang; Giorgio Inghirami; Maurizio DiLiberto; Selina Chen-Kiang; John P Leonard Journal: Blood Date: 2019-01-28 Impact factor: 22.113
Authors: Michael Wang; Javier Munoz; Andre Goy; Frederick L Locke; Caron A Jacobson; Brian T Hill; John M Timmerman; Houston Holmes; Samantha Jaglowski; Ian W Flinn; Peter A McSweeney; David B Miklos; John M Pagel; Marie-Jose Kersten; Noel Milpied; Henry Fung; Max S Topp; Roch Houot; Amer Beitinjaneh; Weimin Peng; Lianqing Zheng; John M Rossi; Rajul K Jain; Arati V Rao; Patrick M Reagan Journal: N Engl J Med Date: 2020-04-02 Impact factor: 91.245