If resistance occurs to second generation TKIs in chronic myeloid leukemia (CML) patients, what is the next best option? Here, Giuseppe Saglio, MD, of the University of Turin, Turin, Italy, explores this important question. He highlights what data from the ENESTnd (NCT00471497) and ENEST1st (NCT01061177) trials have shown in terms of resistance occurence, before discussing the issue of intolerance. This interview was recorded at the 2018 Society of Hematologic Oncology (SOHO) Annual Meeting held in Houston, TX.