Methods for treatment of recurrent hematological malignancies

A method for treating acute myeloid leukemia (AML) or multiple myeloma (MM) in an individual who has been previously treated for AML or MM, wherein the previous treatment was a conventional therapy, and who has been identified as having a genetic aberration that correlates with a poor prognosis for survival selected from the group consisting of a genetic mutation in FLT3 and/or NpM1;

• a rearrangement in an immunoglobulin (Ig) gene and/or T cell receptor gene;
• abnormalities of chromosome 5 or chromosome 7;
• and a complex karyotype, said method comprising (1) obtaining a sample from said individual previously treated for AML or MM and assaying said sample in order to determine whether said individual has said genetic aberration, and (2) administering to said individual who has been determined to have said genetic aberration, at a time when the individual has minimal or non-detectable disease, a therapeutically active amount of a monoclonal anti-Killer Immunoglobulin-like Receptor (KIR) antibody or antigen-binding fragment which binds to KIR2DL1 and KIR2DL2/3 and has the ability to block or neutralize KIR2DL1- and KIR2DL2/3-mediated NK cell inhibition and thereby potentiate NK cell-mediated cytotoxicity, wherein said administration enhances said individual's likelihood of survival, and wherein said anti-KIR antibody or antigen-binding fragment is administered (a) in an amount resulting in substantially complete saturation of KIR2DL1 and KIR2DL2/3 on NK cells for a period of at least about 1 week, at least about 2 weeks, or at least about 1 month;
• and (b) at a dosing frequency of once about every 2 weeks, once about every 1 month or once about every 2 months or longer.