Ponatinib may prove to be particularly advantageous for patients with multiple mutations detectable by mass-spectrometry after tyrosine kinase inhibitor (TKI) resistance, according to a study of 363 patients with refractory chronic myeloid leukemia (CML) and TKI-resistance, including 231 in chronic phase CML. Researchers found:

• Low-level mutations were detected in 53 patients; most, however, did not undergo clonal expansion during ponatinib treatment and no specific individual mutations were associated with inferior outcome.

• The number of mutations detectable by mass-spectrometry after TKI resistance is associated with response to ponatinib treatment and could be used to refine the therapeutic approach.

• Although patients with CP-CML with T315i had superior responses overall, those with multiple mutations detectable by mass-spectrometry had substantially inferior responses vs those with T315i as the sole mutation detected.

• For patients with CP-CML without T315i, the inferior responses seen previously with nilotinib/dasatinib therapy for imatinib-resistant patients with multiple mutations were not seen with ponatinib treatment.

Citation: Parker WT, Yeung DTO, Yeoman AL, et al. The impact of multiple low-level BCR-ABL1 mutations on response to ponatinib. [Published online ahead of print January 14, 2016]. Blood. doi: 10.1182/blood-2015-09-666214.