Introduction

The combination of two non-chemotherapeutic drugs, namely omacetaxine mepesuccinate and venetoclax, can be advantageously used in the treatment of acute myeloid leukemia with nucleophosmin (NPM1) gene mutation, demonstrating a powerful synergistic activity against this form of leukemia, linked to the joint action of the two drugs on key elements for leukemic cell survival and proliferation, including the NPM1 protein itself.

Technical features

The combination of omacetaxine mepesuccinate and venetoclax was used in an experimental protocol for the treatment of a patient with nucleophosmin-mutated acute myeloid leukemia in sixth relapse. The primary objective of this study is to determine the tolerability of the new drug combination and to have preliminary efficacy data. Diffuse infiltration (80%) by leukemic cells was observed on evaluation of the patient’s bone marrow before therapy. During the treatment, apart from the expected haematological toxicity, no other significant toxicities occurred. After the treatment, at the re-evaluation of the disease, a marked reduction of leukemia cells was documented (8%) and a simultaneous recovery of normal bone marrow cells.

Possible Applications

• Treatment of patients with acute myeloid leukemia, particularly with nucleophosmin gene mutation.

Advantages

• A differentiation and growth inhibition effect on leukemic cells, with low toxicity on normal cells;
• A potential antil-eukemic effect, in particular in acute myeloid leukemia with nucleophosmin gene mutation;
• Treatment based on employment of non-chemotherapeutic drugs (chemo-free).