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Lymphoma

Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes

Leukemia volume 29, pages 1578–1586 (2015)Cite this article

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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.

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Acknowledgements

This work was supported by research grants to GL from Genentech and the Deutsche Krebshilfe. In addition, this work was supported by the Deutsche Forschungsgemeinschaft, DFG EXC 1003 Cells in Motion—Cluster of Excellence, Münster, Germany, as well as by a Doctoral Scholarship to MG from the Philipps-University Marburg.

Author information

Authors and Affiliations

  1. Department of Hematology, Oncology and Tumor Immunology, Charité—Universitätsmedizin, Berlin, Germany

    M Pfeifer & B Dörken

  2. Genentech Inc., 1 DNA Way, South San, Francisco, CA, USA

    B Zheng, H Koeppen, R McCord, A Chai, T Sandmann, Y-W Chu, A G Polson & K E Mundt

  3. Division of Translational Oncology, Department of Medicine A, University Hospital Münster, Münster, Germany

    T Erdmann, H Madle & G Lenz

  4. Cluster of Excellence EXC 1003, Cells in Motion, Münster, Germany

    T Erdmann, H Madle & G Lenz

  5. Department of Physics, Philipps-University, Marburg, Germany

    M Grau & P Lenz

  6. Department of Clinical Pathology, Robert-Bosch-Krankenhaus and Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany

    A Staiger & G Ott

  7. Department of Hematology-Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA

    A I Chen

  8. Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USA

    D Lebovic

  9. Hematology Department, Hospices Civils de Lyon - Université de Lyon, Pierre-Bénite, France

    G A Salles

  10. Department of Medicine and Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA

    M S Czuczman

  11. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    M C Palanca-Wessels & O W Press

  12. Seattle Genetics Inc, Bothell, WA, USA

    M C Palanca-Wessels

  13. Stanford University Medical Center, Stanford University, Stanford, CA, USA

    R Advani

  14. Department of Hematology, Centre Hospitalier Régional Universitaire de Lille, Lille, France

    F Morschhauser

  15. Lombardi Comprehensive Cancer Center, Georgetown University Hospital, Washington, DC, USA

    B D Cheson

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  1. M Pfeifer
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Correspondence to K E Mundt or G Lenz.

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Competing interests

BZ, HK, RM, AC, TS, Y-WC, AGP and KEM are employees of Genentech. MCP-W is an employee of Seattle Genetics. GL received research funding from Genentech.

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Pfeifer, M., Zheng, B., Erdmann, T. et al. Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes. Leukemia 29, 1578–1586 (2015). https://doi.org/10.1038/leu.2015.48

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