KMT2A Rearrangements Are Associated with Lineage Switch Following CD19 Targeting CAR T-Cell Therapy

Introduction: Chimeric antigen receptor (CAR) T-cells redirected against CD19 have demonstrated remarkable clinical activity in children and adults with relapsed/refractory (r/r) B-cell malignancies. The risk of lineage switch (LS) following CD19-directed therapies has been well documented but has been primarily limited to case reports. Additionally, the risk of subsequent malignant neoplasms (SMN) following CAR T-cells has not yet been described. Distinguishing LS (B-ALL to myeloid malignancy) from a therapy-related myeloid neoplasm is both clinically and biologically relevant. The former emerges from a highly refractory leukemic clone, likely resistant to salvage therapy, whereas the latter represents a new malignancy that can be associated with long-term survival.