title: Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes.
abstract: Antibody drug conjugates (ADCs), in which cytotoxic drugs are linked to antibodies targeting antigens on tumor cells, represent promising novel agents for the treatment of malignant lymphomas. Pinatuzumab vedotin is an anti-CD22 ADC and polatuzumab vedotin an anti-CD79B ADC that are both linked to the microtubule-disrupting agent monomethyl auristatin E (MMAE). In the present study, we analyzed the activity of these agents in different molecular subtypes of diffuse large B-cell lymphoma (DLBCL) both in vitro and in early clinical trials. Both anti-CD22-MMAE and anti-CD79B-MMAE were highly active and induced cell death in the vast majority of activated B-cell-like (ABC) and germinal center B-cell-like (GCB) DLBCL cell lines. Similarly, both agents induced cytotoxicity in models with and without mutations in the signaling molecule CD79B. In line with these observations, relapsed and refractory DLBCL patients of both subtypes responded to these agents. Importantly, a strong correlation between CD22 and CD79B expression in vitro and in vivo was not detectable, indicating that patients should not be excluded from anti-CD22-MMAE or anti-CD79B-MMAE treatment because of low target expression. In summary, these studies suggest that pinatuzumab vedotin and polatuzumab vedotin are active agents for the treatment of patients with different subtypes of DLBCL.
authors.affiliation: Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Pfeifer
authors.affiliation: Genentech Inc., 1 DNA Way, South San Francisco, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Zheng
authors.affiliation: 1] Division of Translational Oncology, Department of Medicine A, University Hospital Münster, Münster, Germany [2] Cluster of Excellence EXC 1003, Cells in Motion Münster, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Erdmann
authors.affiliation: Genentech Inc., 1 DNA Way, South San Francisco, CA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Koeppen
authors.affiliation: Genentech Inc., 1 DNA Way, South San Francisco, CA, USA.
authors.forename: R
authors.initials: R
authors.lastname: McCord
authors.affiliation: Department of Physics, Philipps-University, Marburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Grau
authors.affiliation: Department of Clinical Pathology, Robert-Bosch-Krankenhaus and Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Staiger
authors.affiliation: Genentech Inc., 1 DNA Way, South San Francisco, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Chai
authors.affiliation: Genentech Inc., 1 DNA Way, South San Francisco, CA, USA.
authors.forename: T
authors.identifier: 0000000266018890
authors.initials: T
authors.lastname: Sandmann
authors.affiliation: 1] Division of Translational Oncology, Department of Medicine A, University Hospital Münster, Münster, Germany [2] Cluster of Excellence EXC 1003, Cells in Motion Münster, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Madle
authors.affiliation: Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Dörken
authors.affiliation: Genentech Inc., 1 DNA Way, South San Francisco, CA, USA.
authors.forename: Y-W
authors.initials: YW
authors.lastname: Chu
authors.affiliation: Department of Hematology-Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
authors.forename: A I
authors.initials: AI
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: D
authors.initials: D
authors.lastname: Lebovic
authors.affiliation: Hematology Department, Hospices Civils de Lyon - Université de Lyon, Pierre-Bénite, France.
authors.forename: G A
authors.initials: GA
authors.lastname: Salles
authors.affiliation: Department of Medicine and Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Czuczman
authors.affiliation: 1] Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA [2] Seattle Genetics Inc, Bothell, WA, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Palanca-Wessels
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: O W
authors.initials: OW
authors.lastname: Press
authors.affiliation: Stanford University Medical Center, Stanford University, Stanford, CA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Advani
authors.affiliation: Department of Hematology, Centre Hospitalier Régional Universitaire de Lille, Lille, France.
authors.forename: F
authors.initials: F
authors.lastname: Morschhauser
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University Hospital, Washington DC, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Cheson
authors.affiliation: Department of Physics, Philipps-University, Marburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Lenz
authors.affiliation: Department of Clinical Pathology, Robert-Bosch-Krankenhaus and Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Ott
authors.affiliation: Genentech Inc., 1 DNA Way, South San Francisco, CA, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Polson
authors.affiliation: Genentech Inc., 1 DNA Way, South San Francisco, CA, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Mundt
authors.affiliation: 1] Division of Translational Oncology, Department of Medicine A, University Hospital Münster, Münster, Germany [2] Cluster of Excellence EXC 1003, Cells in Motion Münster, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Lenz
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D051925:CD79 Antigens / Q000235:genetics / Q000276:immunology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017321:Clinical Trials, Phase I as Topic; D015331:Cohort Studies; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000235:genetics / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; C497867:CD22 protein, human; D051925:CD79 Antigens; C497883:CD79B protein, human; D018796:Immunoconjugates; D051918:Sialic Acid Binding Ig-like Lectin 2