Taking a BiTE Out of ALL by Targeting CD19

One of the confounding issues with treating patients with immunotherapy for hematologic diseases is the risk of relapse that can occur during and after treatment. Researchers from Hubertus Wald Tumorzentrum/University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, tried a new targeted therapy to treat the 10% to 20% of patients with acute lymphoblastic leukemia (ALL) that experience relapse.

Braig, Brandt, Goebeler, et al., analyzed four CD19-negative ALL relapses after treatment with the CD19/CD3 bispecific T-cell engager (BiTE) blinatumomab, the results of which were first published in Blood, the journal for The American Society of Hematology (ASH).

Three relapses occurred during treatment, with the CD19-negative escape variant first detected after two treatment courses. In one patient, the CD19-negative clone appeared more than a year (19 months) after completion of blinatumomab treatment. A thorough molecular workup of one 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. All four cases showed a cellular phenotype identical to the primary diagnosis except for CD19 negativity.

The research team concluded that CD19 membrane trafficking may disrupt resistance to BiTE. Membrane trafficking occurs when proteins and other macromolecules are distributed throughout the cell, and released to or internalized from the extracellular space.

Further research with more patients with the same type of leukemia may reveal more of the efficacy and safety of BiTE to mitigate this issue of resistance.

Approximately 6,590 people of all ages (3,590 men and boys and 3,000 women and girls) in the United States will be diagnosed with ALL this year, according to Cancer.Net. Athough most cases of ALL occur in children, about 4 out of 5 deaths from ALL will occur in adults. An estimated 1,430 deaths (800 men and boys and 630 women and girls) will occur this year. The good news is that the 5-year survival rate of people of all ages with ALL increased from 41% for those diagnosed from 1975–1977 to 70% for those diagnosed from 2004 to 2010.