At ASH 2025 we presented management and outcomes of patients with blast phase chronic myeloid leukaemia through the multicentre analysis by the H. Jean Khoury Cure CML Consortium. The management of blast phase CML is diverse, it depends on which institution and which country patients are being treated at. Then the consensus guidelines for management for blast phase CML are scarce. Hence we undertook this study through the Cure CML Consortium to study the treatment patterns and outcomes of patients with blast phase CML.

What was the study design?

This a multi-institutional retrospective study. All patients diagnosed with blast phase CML, which was based on the modified MD Anderson criteria which included blasts over 30% either in the blood or the bone marrow, or if they had extramedullary disease, from 2010-2025 were included. Data was individually collected by personnel at 11 different institutions and shared through a data use agreement.

It was a retrospective design and for statistical analysis we used a chi-squared test for categorical variables and then overall survival and event free survival was computed using the Kaplan-Meier method. Then we also used a landmark analysis at a 6-month cut-off timepoint to associate the outcomes for patients that had undergone a stem cell transplant by that 6-month mark.

What were the results?

This is an exciting compilation of patients. This is the largest study for blast phase CML that has been done in the US. A total of 288 patients were included in the study, the median age at diagnosis was 50 years. There was a good inclusion of males/females. The majority of the patients were Caucasian, about 67%, there were 20% African American followed by 5% Hispanic and 3% Asian.

We found that the majority of the patients, which were 64%, were treated with a combination of TKI and chemotherapy. The chemotherapy used depended on whether it’s myeloid phase or lymphoid blast phase. 7+3 was the most commonly used chemotherapy regimen for myeloid blast phase and hyper-CVAD for lymphoid blast phase.  There were a few patients, about 22%, that were treated with TKI alone and 8% with chemotherapy alone.

In terms of the TKI use, dasatinib and ponatinib were the most common TKIs that were used, whether alone or in combination, followed by bosutinib, nilotinib or ermatinib.

Then, looking at outcomes, we did see that about 60% of patients were able to achieve either a complete cytogenetic remission or a BCR-ABL less than 1%. The overall survival was 19.7 months and with a five-year overall survival rate of 38%.

In terms of association with various variables and its impact on overall survival and event free survival, we performed a multivariable analysis and we saw that the patients that were over 50 years of age had a significantly shorter overall survival compared to patients that were less than 50 years of age. For treatment, using a TKI and chemotherapy followed by a stem cell transplant did not significantly prolong survival compared to TKI alone. Patients that had myeloid phenotype had a worse overall survival compared to patients that had a lymphoid phenotype. This could have been confounded by the amount of patients that went to transplant – only 31% went to transplant by the six-month mark, but these are encouraging results for patients. Hence, using a TKI followed by a stem cell transplant is still an accepted standard for management of patients with blast phase CML.

What is the clinical significance of these results and what is next for this study?

The clinical significance of this is that we always want to base our treatment decisions for patients with blast phase CML on not just their age but also comorbidities. But age still continues to play an important factor in outcomes. So patients that are younger than 50 years of age using a combination of TKI and chemotherapy and getting them to transplant. Then even for those that are 50 years of age the same applies, however, their survival can potentially be shorter compared to patients that are less than 50.

The other important part is that we always discuss what TKI should be used in combination with chemotherapy now we have first generation, second generation and third generation TKIs and third generation ponatinib is being used more commonly. In our study both dasatinib and ponatinib were used and the impact of which generation of TKIs was used for treatment was not significant. So it also depends on which TKI they’ve been exposed to in the past for chronic phase CML and whether this was a de novo blast phase CML or they’ve progressed from a prior chronic phase CML. If they’ve been exposed to second generation TKI before we are more likely to not use a second generation TKI for their treatment.

Then it was also interesting to note that on multivariable analysis the addition of chemotherapy did not make a significant difference in overall survival. However, we need to continue to study this to see if we can decrease the amount of chemotherapy we’re giving to our patients with the aim to get them to transplant in the end.