ASH 2025 | Second-line therapy outcomes in CML after frontline second-generation TKI failure
Fadi Haddad, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses outcomes of patients with chronic myeloid leukemia (CML) who required second-line therapy after frontline second-generation tyrosine kinase inhibitors (TKIs). Dr Haddad highlights that most patients achieved meaningful responses after switching treatment, with particularly favorable outcomes seen with newer-generation TKIs. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
In this abstract, we look at patients who received a frontline treatment for their chronic myeloid leukemia with a second-generation TKI, whether it was the dasatinib, bosutinib, or nilotinib. And then, we look at their outcomes after they moved to a second-line treatment. They could have switched to a second-line therapy because of toxicity, because of disease resistance, or both, or sometimes for other reasons...
In this abstract, we look at patients who received a frontline treatment for their chronic myeloid leukemia with a second-generation TKI, whether it was the dasatinib, bosutinib, or nilotinib. And then, we look at their outcomes after they moved to a second-line treatment. They could have switched to a second-line therapy because of toxicity, because of disease resistance, or both, or sometimes for other reasons. And then we found that almost 40% of the patients did switch from a frontline second-generation TKI to a second-line therapy because of side effects, and maybe a quarter of the patients because of disease resistance. And when I say disease resistance, it’s either patients who never achieved a cytogenetic response, or they achieved a cytogenetic response, but they lost it later on during the course of therapy. And in patients who had disease resistance, 12% of them had a mutation, most frequently the T315I mutation. Then we looked at the second-line treatment those patients received. Most frequently it was imatinib in 26% of them, followed by bosutinib in 23%, then some other second-generation TKIs, ponatinib in maybe 11% of the patients, and asciminib in 2% of the patients. Now what were their outcomes? After switching to second-line treatment, we divided those patients into two groups, those who were not in a cytogenetic response and those who were already in a cytogenetic response or deeper. Patients who were not in a cytogenetic response, 60% of them achieved a cytogenetic response after receiving a second-line treatment, and patients who were in a cytogenetic response or deeper went ahead and further deepened their responses and close to 90% of them achieved a deeper response following second-line treatment. The survival of those patients and the response rates were better in those who received either ponatinib or asciminib. So this study tells us that two key messages. Number one, among patients who have true disease resistance, 60 to 70% of them will eventually respond to a second-line treatment. But also it tells us that in the second-line setting, among those who have disease resistance, treatment with third-generation TKI, such as ponatinib and asciminib was associated with a better survival and better response rates. Actually, 77% of those patients achieved a major molecular response.
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