Immunotherapy of recurrent B-cell malignancies after allo-SCT with Bi20 (FBTA05), a trifunctional anti-CD3 x anti-CD20 antibody and donor lymphocyte infusion.
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 microg) 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 microg. 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.
Department of Medicine III, University of Munich-Grosshadern, Munich, Germany. buhmann@biolink.de
R
R
Buhmann
B
B
Simoes
M
M
Stanglmaier
T
T
Yang
M
M
Faltin
D
D
Bund
H
H
Lindhofer
H-J
HJ
Kolb
D019264:Adoptive Transfer; D000328:Adult; D018033:Antibodies, Bispecific / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000453:epidemiology / Q000628:therapy*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012008:Recurrence; D014019:Tissue Donors; D014184:Transplantation, Homologous
D018033:Antibodies, Bispecific; C530113:Bi20 antibody