PS1193 CHARACTERISTICS AND OUTCOMES OF THE TREATMENT PATIENTS WITH T315I MUTATION CML

Abstract

Background:Resistance to tyrosine kinase inhibitors (TKI) in patients with chronic myeloid leukemia (CML) is frequently caused by point mutations in the BCR‐ABL kinase domain, including the gatekeeper mutant T315I, which confers a high degree of resistance to all currently approved tyrosine kinase inhibitors except ponatinib.Aims:To evaluate the results of different treatments in CML patients with mutation T315I.Methods:Retrospective analysis of 79 BCR‐ABLT315I ‐positive CML patients (pts) was done. Allogeneic bone marrow transplantation (allo‐HSCT) was made in 20 pts, 59 pts received only pharmacological therapy (41 pts received TKI as monotherapy or in combination with other drugs, 10‐ α‐IF, other 8 pts received hydroxyurea or chemotherapy). At the time of allo‐HSCT 6 pts were in CP 1, 7‐ CP≥2, 6 pts had AP and 3 pts were in BC. Median (Me) age at the time of mutation detected was 42 years (13–75) (38 years in HSCT‐group). In allo‐HSCT group 13 pts had unrelated donors, 13(65%) pts received more than 2 lines TKIs before HSCT. The number of points on EBMT scale: 3–4 points ‐ 16 pts, 5–7 points ‐ 6 pts. Conditioning regimen in 13 (70%) pts had reduced intensity. Me time to HSCT after T315I detection was 7 months (0–72).Results:Me follow‐up time after T315I detection was 21 months (1–100). 5‐years OS in whole group was 42%. According to multivariate analysis only CML phase at the time of mutation detection significantly affect to survival in whole group. All pts in BC (n = 7), 3 in HSCT group and 4 in non‐HSCT group, died within first year after T315I indication wherein Me survival time was 1,3 month. 5‐years OS in non‐HSCT group (n = 59) was 42% with Me survival time 2,8 years. 5‐years OS after allo‐HSCT (n = 20) was 37% with Me survival time 5 months. However, 7 pts live more than 2 years after allo‐HSCT, 2 ‐ more than 6 years. All living patients after allo‐HSCT are in deep molecular response. Pts in the 2nd CP have OS 47% (CI 95% 29–53%), p = 0.46. There was no significant difference in 5‐years OS between TKI (n = 41) and non‐TKI (n = 18) pharmacological therapy (non‐HSCT) groups (42% and 47% respectively, p = 0,53). In the group that received α‐interferon in the combination with other drugs (n = 10), the 5‐year OS is higher than in the group that did not receive interferon therapy (n = 49), 72% vs 45%, respectively (p = 0.21).Summary/Conclusion:Detection of T315I mutation in TKI‐resistant patients is extremely unfavorable factor for survival, and it is a great reason for switching to ponatinib or other new potential investigated drugs if possible. Allo‐HSCT is an effective method of treatment for this group of patients in case of good selection taking into consideration transplant risk, especially for patients in CP ≥2. The administration of pharmacological therapy in the 1st CP is an effective method of treatment, which allows to control the disease for a long time.