1940 - Outcomes of chronic myeloid leukemia with T315I mutation in the absence of targeted therapy or hematopoietic stem cell transplantation

Background

Few chronic myeloid leukemia (CML) patients may stop responding to tyrosine kinase inhibitors (TKI). On mutational analysis, the most common mutation detected is T315I conferring resistance to all TKIs except ponatinib, availability of which is limited. Management of these patients, in the absence of ponatinib is allogenic hematopoietic stem transplantation. Data on outcomes of the patients with this mutation in the absence these modalities is limited. The present study was planned to study the profile and outcomes of CML patients with T315I mutation treated with hydroxyurea and supportive care.

Methods

Data of CML patients with T315I mutation who failed on imatinib diagnosed between 2004 and 2018 was retrospectively analyzed.

Results

A total of 2162 patients were analyzed. Of these, 312 (14.4%) were imatinib failures. Mutations were seen in 120 (38.5%) patients, of which 45 (37.5%) patients had T315I mutation. Reasons for mutational analysis testing were not attaining MMR at 1 year, loss of molecular response and loss of hematological response in 3(6.7%), 35(77.8%) and 7(15.6%) patients respectively. The median duration from diagnosis to T315I detection was 38 months (range, 6-146). At the time of detection of T315I mutation, CP, AP and BP were detected in 19 (42.2%), 12(26.7%) and 14 (31.1%) patients respectively. At a median follow up of 18 months, 19 patients were alive and 26 patients were dead with a median overall survival (mOS) of 18 months (range, 0-122). mOS of patients with CP, AP and BP were not reached (range, 2-122) 12 (range, 1-81) and 3 (range, 0.3-34) months respectively (p = 0.001). Table.Table: 1096P

Conclusions

T315I was the most common mutation detected in patients who had not attained MMR or progressed on imatinib. Majority of patients were in chronic phase at time of T315I detection. Phase at the time of detection of T315I had significant impact on outcomes in the absence of targeted therapy or allogenic stem cell transplantation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Nizam’s Institute of Medical Sciences.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.