Increase of PD-L1 expressing B-precursor ALL cells in a patient resistant to the CD19/CD3-bispecific T cell engager antibody blinatumomab

• DOI: 10.1186/s13045-015-0213-6
• Publication Date: 2015-10-08T12:38:01Z
• Authors: Thomas Köhnke; Christina Krupka; Johanna Tischer; Thomas Knösel; Marion Subklewe
• Keywords: Blinatumomab; Hematology

The bispecific T cell engager blinatumomab has shown encouraging clinical activity in B-precursor acute lymphoblastic leukemia (ALL). However, about half of relapsed/refractory patients do not respond to therapy. Here, we present the case a 32-year-old male patient with refractory ALL who was resistant treatment blinatumomab. Bone marrow immunohistochemistry revealed infiltrates and an increase programmed death-ligand 1 (PD-L1)-positive cells as potential immune escape mechanism. We were able recapitulate observation vitro by showing that mediate cytotoxicity CD19-positive using autologous cells. In contrast, addition healthy donor led lysis These results strongly encourage further systematic evaluation checkpoint molecules cases failure might highlight possible mechanism overcome resistance this otherwise highly effective treatment.