Combination treatment of chronic myelomonocytic leukemia in patients with ras pathway mutations

Abstract

Provided herein are methods for treating a subject having chronic myelomonocytic leukemia (CMML), the method comprising: (a) identifying a RAS pathway mutation in tumor cells of the subject, wherein the RAS pathway mutation is a NRAS, KRAS, PTPN-11 and/or CBL mutation; (b) identifying a dominant CBL mutation of CBL variant allele frequency of from <5% to >10%; and (c) administering to the subject identified in step (a) a therapeutically effective amount of an anti-hGM-CSF antibody. Also provided herein are methods for treating a subject having chronic myelomonocytic leukemia (CMML), the method comprising: (a) identifying a RAS pathway mutation in tumor cells of the subject, wherein the RAS pathway mutation is a NRAS, KRAS, PTPN-11 and/or CBL mutation; (b) identifying a dominant CBL mutation of CBL variant allele frequency of from <5% to >10%; and (c) administering to the subject identified in step (a) a therapeutically effective amount of an anti-hGM-CSF antibody lenzilumab and a therapeutically effective amount of a second therapeutic agent. The subject may have a RAS pathway mutation or a RAS pathway mutation and at least one TET2 mutation identified in the tumor cells, an increased percentage of CD116 and CD131 in CD34+ stem and progenitor cells in the subject compared to a healthy subject and/or an increased percentage of CD14+ cells in the subject compared to a healthy subject. A therapeutically effective amount of a hypomethylating agent or hydroxyurea may be further administered according to the provided methods.

Dependencies are inferred from the claim text.