The Combination of Ponatinib and Alpha-Interferon can Improve Outcome of Resistant Chronic Myeloid Leukemia Patients

Abstract

The most of patients affected by chronic myeloid leukemia is cured with Tyrosine Kinase Inhibitors (TKI). However, about 30% must change therapies for intolerance or poor efficacy. The failure of therapy is associated in the majority of cases to the appearance of ABL1 mutations. Ponatinib (ICLUSIG, INCYTE^®) is able to overcome most of the known mutations, including the T315I. But when compound mutations appear, the TKIs alone are not enough and a combination therapy is required to overcome this condition.

We describe here the evolution of the mutational status of 3 patients with compound mutations, treated with the association of ponatinib plus alfa interferon. This combination resulted safe and effective for all.

In the first patient, the T315I plus the V289A and the M244V mutations were discovered; the second patient showed the T315I plus the A288T and the G390R and the third one, without T315I, the K419E plus the G254R were found. After one year of the combination therapy, all cases showed the disappearanced of the compound mutations and the T315I. In addition, the use of next generation sequencing resulted fundamental for detecting and monitoring resistant patients.