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Title: Single-agent activity of phosphatidylinositol 3-kinase inhibition with copanlisib in patients with molecularly defined relapsed or refractory diffuse large B-cell lymphoma.
Authors: Lenz, Georg;Hawkes, Eliza A;Verhoef, Gregor;Haioun, Corinne;Thye Lim, Soon;Seog Heo, Dae;Ardeshna, Kirit;Chong, Geoffrey;Haaber, Jacob;Shi, Wei;Gorbatchevsky, Igor;Lippert, Susanne;Hiemeyer, Florian;Piraino, Paolo;Beckmann, Georg;Peña, Carol;Buvaylo, Viktoriya;Childs, Barrett H;Salles, Gilles
Affiliation: Department of Medicine A, Hematology, Oncology, and Pneumology, University Hospital Münster, Münster, Germany
Bayer HealthCare Pharmaceuticals, Inc., Whippany, NJ, USA
University Hospitals Leuven, Leuven, Belgium
Ballarat Regional Integrated Cancer Centre, Ballarat, VIC, Australia
Eastern Health Clinical School, Monash University, Melbourne, VIC, Australia
Lymphoid Malignancies Unit, Groupe Hospitalier Henri Mondor-Albert Chenevier, Creteil, France
National Cancer Centre Singapore and Duke-NUS Medical School, Singapore, Singapore
Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
University College London Hospitals NHS Foundation Trust, London, UK
Department of Hematology, Odense University Hospital, Odense, Denmark
Bayer China, Beijing, China
Pharmaceuticals Division, Bayer AG, Berlin, Germany
Hospices Civils de Lyon, Université de Lyon, Centre Hospitalier Lyon-Sud, Service d'hématologie, Lyon, France
Olivia Newton-John Cancer Wellness and Research Centre, Austin Health, Heidelberg, Victoria, Australia
Issue Date: 14-Feb-2020
EDate: 2020-02-14
Citation: Leukemia 2020; online first: 14 February
Abstract: Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have adverse outcomes. We evaluated the efficacy and safety of the phosphatidylinositol 3-kinase inhibitor copanlisib in patients with relapsed/refractory DLBCL and assessed the relationship between efficacy and DLBCL cell of origin (COO; activated B-cell like [ABC] and germinal center B-cell like [GCB]) and other biomarkers. The primary endpoint was objective response rate (ORR) in DLBCL COO subgroups (ABC, GCB, and unclassifiable) and by CD79B mutational status (NCT02391116). Sixty-seven patients received copanlisib (ABC DLBCL, n = 19; GCB DLBCL, n = 30; unclassifiable, n = 3; missing, n = 15). The ORR was 19.4%; 31.6% and 13.3% in ABC and GCB DLBCL patients, respectively. ORR was 22.2%/20.0% for patients with/without CD79B mutations (wild type, n = 45; mutant, n = 9; missing, n = 13). Overall median progression-free survival and duration of response were 1.8 and 4.3 months, respectively. Adverse events included hypertension (40.3%), diarrhea (37.3%), and hyperglycemia (32.8%). Aberrations were detected in 338 genes, including BCL2 (53.7%) and MLL2 (53.7%). A 16-gene signature separating responders from nonresponders was identified. Copanlisib treatment demonstrated a manageable safety profile in patients with relapsed/refractory DLBCL and a numerically higher response rate in ABC vs. GCB DLBCL patients.
DOI: 10.1038/s41375-020-0743-y
ORCID: 0000-0002-9541-8666
PubMed URL: 32060403
Type: Journal Article
Appears in Collections:Journal articles

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