1098P - Incidence of imatinib resistance in chronic myeloid leukemia (CML) patients: Experience from resource poor center of eastern India

Abstract

BackgroundThe management of Chronic Myeloid Leukemia (CML) has undergone a paradigm shift with advent of the tyrosine kinase inhibitor (TKI), namely imatinib. Despite a high remission rate, a significant proportion of patients showed resistance and/or intolerance to imatinib therapy, be it primary or secondary. However, the scenario of resistance along with the prevalence and clinical route of CML in the Eastern part of India remains elusive. To observe the incidence of resistance to TKI after years of therapy, we performed a study in a tertiary cancer care centre, serving patients from Eastern Indian states as well as neighbor countries like Bangladesh and Bhutan. Based on the CML cases registered at the centre for the last 13 years, we performed a longitudinal assessment of the disease history and molecular management to portray the incidence of imatinib resistance in CML patients.Table: 1098PTable: 1098PNo. of registered CML cases (2005-2017)Median period of Imatinib treatmentNo. of patients showing Loss of MMR (BCR-ABL >1.0%)No. of patients undergoing BCR-ABL KD mutation testing (% affordability)No. of patients showing BCR-ABL KD mutationPatients with Imatinib failure but no detectable BCR-ABL KD mutation98626 months10120 (20%)11 (55% of resistant pool)9 (45% of resistant pool) MethodsThe methods in schematic are described below: No. of CML cases with disease history ↓ Patients showing loss of Major Molecular Response (MMR), detected by Real-Time quantitative PCR ↓ Mutation analysis in BCR-ABL kinase domain (KD) (by Sanger sequencing) ↓ Calculation of type and incidence of KD mutation ↓ The survival analyses performed by Kaplan-Meier analysis. ResultsThe results are presented in tabular form as below:.After years of therapy, KD mutations are seen in 55% of imatinib-resistant patients. The survival analysis showed significant difference between treatment-sensitive and –resistant pools. ConclusionsThe incidence of imatinib resistance has been increasingly detected in Eastern-Indian region after long term therapy with imatinib. However, the full scenario could not be depicted due to resource constraints. More numbers of patients are to be tested to achieve robust evidence. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.