Abstract 1940
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
Characteristic | N (%) |
---|---|
Median age (years) | 37 (range, 6-60) |
Gender Males Females | 32 13 |
Phase CP AP BP | 35 (77.8) 8 (17.8) 2 (4.4) |
EUTOS risk Low High | 22 (48.9) 23 (51.2) |
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.
Resources from the same session
3317 - Circulating tumor DNA (ctDNA) analysis in patients (pts) with non-small cell lung cancer (NSCLC) treated with telisotuzumab vedotin (teliso-v), an antibody-drug conjugate targeting c-Met
Presenter: Rebecca Heist
Session: Poster Display session 1
Resources:
Abstract
3887 - First Real Life Data on Durvalumab after definitive concomitant ChemoRadiotherapy (cCRT) in unresectable Stage (St) III Non-Small Cell Lung Cancer (NSCLC) in France: Analysis of 591 patients (pts) enrolled in the French cohort (c) Temporary Authorization of Use (ATU)
Presenter: Virginie Avrillon
Session: Poster Display session 1
Resources:
Abstract
682 - EGFR Inhibitor Versus Chemotherapy as Adjuvant Treatment for Locally-advanced EGFR-mutant Non-Small Cell Lung Cancer
Presenter: Peng Xie
Session: Poster Display session 1
Resources:
Abstract
2509 - Afatinib in EGFR TKI-naïve patients with EGFR mutation-positive (EGFRm+) NSCLC: interim analysis of a Phase IIIb, multi-national, open-label study
Presenter: Filippo de Marinis
Session: Poster Display session 1
Resources:
Abstract
3300 - First-line ceritinib versus chemotherapy in patients (pts) with advanced ALK rearranged (ALK+) non-small cell lung cancer (NSCLC): ASCEND-4 Asian subgroup analysis
Presenter: Daniel SW Tan
Session: Poster Display session 1
Resources:
Abstract
2653 - A combined analysis of two Phase IIIb studies of afatinib in EGFR TKI-naïve patients (pts) with EGFR mutation-positive (EGFRm+) NSCLC
Presenter: Filippo de Marinis
Session: Poster Display session 1
Resources:
Abstract
3663 - Impact of plasma EGFR mutation fractions on response to first generation tyrosine-kinase inhibitor in treatment of naïve non-small cell lung cancer patients
Presenter: Xiaohong Wang
Session: Poster Display session 1
Resources:
Abstract
5921 - Definition of an afatinib trough concentration threshold in the treatment of NSCLC
Presenter: Stephane Bouchet
Session: Poster Display session 1
Resources:
Abstract
2852 - A Phase Ib Trial of Neoadjuvant Chemoradiotherapy and Durvalumab(MEDI4736) for Potentially Resectable stage III Non-Small Cell Lung Cancer (NSCLC)
Presenter: Beung chul AHN
Session: Poster Display session 1
Resources:
Abstract
3273 - Low expression of Notch1 and combined Notch1/HES1 are associated with adverse survival factor for limited stage small cell lung cancer
Presenter: Jinsoo Lee
Session: Poster Display session 1
Resources:
Abstract