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Allografting

Immunotherapy of recurrent B-cell malignancies after allo-SCT with Bi20 (FBTA05), a trifunctional anti-CD3 × anti-CD20 antibody and donor lymphocyte infusion

Bone Marrow Transplantation volume 43, pages 383–397 (2009)Cite this article

Abstract

Donor lymphocyte infusions (DLIs) after allo-SCT displayed limited use in CLL and highly malignant non-Hodgkin's lymphoma (NHL). Here we studied whether Bi20 (FBTA05), a novel trifunctional bispecific antibody targeting CD20 on lymphoma cells and CD3 on T cells, could induce GVL responses in combination with DLI or mobilized PBSCT after allogeneic transplantation in these diseases. Six patients (three cases with p53-mutated CLL and three with high-grade NHL (HG-NHL)) refractory to standard therapy were treated with escalating doses of Bi20 (range 10–2000 μg) followed by DLI or SCT. Thereby, all CLL patients showed a prompt but transient clinical and hematological response. In one patient with HG-NHL, we observed a halt in progression for almost 4 months. Side effects (fever, chills and bone pain) were tolerable and appeared at antibody dose levels between 40 and 200 μg. The cytokine profile was characterized by transient increases of IL-6, IL-8 and IL-10. Neither human anti-mouse antibodies nor GVHD developed, allowing repeated treatment courses. In summary, the trifunctional antibody Bi20 induced prompt antitumor responses in extensively pretreated, p53-mutated alemtuzumab and rituximab refractory patients indicating its therapeutic potential.

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Acknowledgements

This study is supported by grants of the Deutsche José Carreras Leukämie-Stiftung eV (DJCLS R 06/23) to Raymund Buhmann and Hans-Jochem Kolb; B Simoes is supported by grant 01/04492-8 FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo), Brasil; T Yang is supported by a fellowship of the German Academic Exchange Service (DAAD). We are indebted to many nurses and physicians for unconditional assistance in patient care, referral of patient material and data collection.

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Author notes

  1. R Buhmann, B Simoes and M Stanglmaier: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine III, University of Munich-Grosshadern, Munich, Germany

    R Buhmann, B Simoes & H-J Kolb

  2. Helmholtz Center Munich, German Research Center for Environmental Health (GmbH)/Clinical Cooperative Group Haematopoietic Cell Transplantation (CCG-HCT), Munich, Germany

    R Buhmann, B Simoes, T Yang, D Bund & H-J Kolb

  3. TRION Research GmbH, Martinsried, Germany

    M Stanglmaier & M Faltin

  4. TRION Pharma GmbH, Munich, Germany

    H Lindhofer

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  1. R Buhmann
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Correspondence to R Buhmann.

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Buhmann, R., Simoes, B., Stanglmaier, M. et al. Immunotherapy of recurrent B-cell malignancies after allo-SCT with Bi20 (FBTA05), a trifunctional anti-CD3 × anti-CD20 antibody and donor lymphocyte infusion. Bone Marrow Transplant 43, 383–397 (2009). https://doi.org/10.1038/bmt.2008.323

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