CD19− relapses are a major challenge in about 10% to 20% of patients treated with blinatumomab.
Molecular workup of 1 case revealed a disrupted CD19 membrane export as the basis for blinatumomab resistance.
The CD19 antigen is a promising target for immunotherapy of acute lymphoblastic leukemia (ALL), but CD19− relapses remain a major challenge in about 10% to 20% of patients. Here, we analyzed 4 CD19− ALL relapses after treatment with the CD19/CD3 bispecific T-cell engager (BiTE) blinatumomab. Three were on-drug relapses, with the CD19− escape variant first detected after only 2 treatment courses. In 1 patient, the CD19− clone appeared as a late relapse 19 months after completion of blinatumomab treatment. All 4 cases showed a cellular phenotype identical to the primary diagnosis except for CD19 negativity. This argued strongly in favor of an isolated molecular event and against a common lymphoid CD19− progenitor cell or myeloid lineage shift driving resistance. A thorough molecular workup of 1 of the cases with early relapse confirmed this hypothesis by revealing a disrupted CD19 membrane export in the post–endoplasmic reticulum compartment as molecular basis for blinatumomab resistance.
- Submitted May 25, 2016.
- Accepted October 11, 2016.
- © 2017 by The American Society of Hematology
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