Dasatinib Produces Lengthy Remissions of Extramedullary Leukemia: A Retrospective Observational Study

Since 2004, patients receiving imatinib with relapse in non-marrow sites were given dasatinib to preserve control of leukemic marrow. Remissions in CNS and other organs began to be reported and are continuously observed to present. With resistance to one BCR::ABL1 tyrosine kinase inhibitor and sensitivity to a dual BCR::ABL1/SRC inhibitor recognized, we undertook a retrospective observational study of all reported patients with EML given dasatinib ± routine therapies used over 50 years. We elicited remission durations from authors. One hundred and sixty-three patients (150 Ph'+, 13 Ph'- negative leukemias) received dasatinib ± conventional EML treatments. All but six cases reported disappearance of EML involvement, documented by MRI, CSF, PET/CT in 10, and autopsy in 2. To date, 36 EML remissions have lasted 2+-11+ years (15 > 4 years). Thirty-four of the responding patients had post-dasatinib transplants and 3 CAR-T therapy. The tyrosine kinase inhibitor overexpressed in our prior RNAseq studies of EML tissue was LCK, a SRC kinase target of dasatinib known to be present in CNS, nerves, and some cancers. We present published data to support LCK as one possible tissue target in EML. As there has never been any durably effective treatment for EML, these observations merit prospective trials to validate the observed success of dasatinib and determine the role of additional therapies including cellular therapies. Dasatinib is a potentially practice-changing targeted therapy for EML. Finding and eradicating EML could increase the possibility of lengthy disease-free survival.