Combination of an arsenic compound and at least one retinoid for treating acute myeloid leukemia
The present invention relates to methods and pharmaceutical compositions for the treatment of acute myeloid leukemia. In particular, the present invention relates to a method for treating NPM-1-driven acute myeloid leukemia (AML) in a subject in need thereof comprising administering the subject with a therapeutically effective amount of at least one arsenic compound and with a therapeutically effective amount of at least one retinoid.
1. A method for reversing, alleviating, or inhibiting the progress of acute myeloid leukemia (AML) driven by mutation of the NPM-1 gene in a subject in need thereof comprising administering to the subject a therapeutically effective amount of at least one arsenic compound and a therapeutically effective amount of at least one retinoid, wherein the subject has a normal karyotype, wherein the therapeutically effective amount of the at least one arsenic compound provides a serum concentration of 0.1 μM to 1 μM, wherein the therapeutically effective amount of the at least one retinoid provides a serum concentration of 0.3 μM to 1 μM, wherein the subject is not receiving chemotherapy prior to said administering step, and wherein the at least one arsenic compound is arsenic trioxide (As 2 O 3 ) and the at least one retinoid is a retinoic acid.
2. The method of claim 1 , wherein the ratio of As 2 O 3 to retinoic acid administered to the subject is from 1:1 to 1:3.
3. A method for reversing, alleviating, or inhibiting the progress of acute myeloid leukemia (AML) driven by mutation of the NPM-1 gene in a subject in need thereof comprising administering to the subject a therapeutically effective amount of at least one arsenic compound and a therapeutically effective amount of at least one retinoid, wherein the subject has a normal karyotype, wherein the therapeutically effective amount of the at least one arsenic compound provides a serum concentration of 0.1 μM to 1 μM, wherein the therapeutically effective amount of the at least one retinoid provides a serum concentration of 0.3 μM to 1 μM, wherein the at least one arsenic compound and the at least one retinoid are administered without any other chemotherapeutic agent, and wherein the at least one arsenic compound is arsenic trioxide (As 2 O 3 ) and the at least one retinoid is a retinoic acid.
4. The method of claim 3 , wherein the ratio of As 2 O 3 to retinoic acid administered to the subject is from 1:1 to 1:3.