BCP-ALL blasts are not dependent on CD19 expression for leukaemic maintenance

Resistance to anti-CD19/CD3 BiTE in acute lymphoblastic leukemia may be mediated by disrupted CD19 membrane trafficking

“…3,[7][8][9] Also, in patients after chemotherapy or transplantation, diminished CD19 expression (but not loss of CD19) has been previously described on relapse blasts, 10 also confirming the notion that this antigen is not essential for leukemia maintenance. 11 The mechanisms underlying the emergence of CD19 2 escape variants are insufficiently understood to date but should be elucidated because this may have implications for the optimization of CD19directed immunotherapies. In patients treated with CART-19, genetic alterations and alternatively spliced, truncated CD19 variants have been described to account for resistance.…”

CAR T cell immunotherapy in hematology and beyond

“…Relapses are either due to limited persistence of CAR T cells in the circulation, or to the loss of the CD19 target antigen on the malignant clone. Specifically, malignant B cells can escape CD19targeting therapies by loss of full-length CD19 [36][37][38], by an isoform switch to splice variants lacking extracellular antibody recognition domain of CD19 [39], or by undergoing a lineage switch to a CD19-negative, myeloid disease phenotype [40]. Antigen-negative relapses occur at an estimated frequency of about 20%.…”

Epidemiology and biology of relapse after stem cell transplantation

“…73 It is highly likely that these processes of niche remodelling and epigenetic plasticity are relevant in allowing cells to survive graft vs leukemia effects and immune-targeted therapies. 74 Escape mutants to CAR T-cells or monoclonal antibodies such as blinatumomab have been commonly reported 75,76,77 and although some may have a genetic basis, it is well established that tumor microenvironments can influence the function of immune effector cells. 78 …”