PS1184 ANALYSIS OF BCR‐ABL1 TRANSCRIPT LEVELS AT 3 MONTHS IN PREDICTING OVERALL RESPONSE IN PATIENTS OF CHRONIC MYELOID LEUKEMIA‐ CHRONIC PHASE ON 1ST LINE THERAPY WITH IMATINIB MESYLATE

Background: Majority of patients with Chronic myeloid leukemia in chronic phase gain substantial benefit from imatinib, but some fail to respond or lose their initial response. European Leukemia Net recommendations help to identify patients responding poorly to imatinib. Response is assessed with standardized RT‐PCR and/or cytogenetics at 3, 6, and 12 months following start of therapy. At 3 months ‘warning response’, recommendations are to continue same therapy and monitor for disease progression. However newer evidences suggest that patients who show suboptimal response with imatinib do so early in assessment and hence, 1 st 3 and 6 month assessment might be most useful in predicting treatment failure. Aims: 1. To study the rate of cytogenetic and molecular responses after 6, and 12 months of treatment with Imatinib in newly diagnosed CML‐CP patients 2. To study the effect of BCR‐ABL1 transcript levels at 3 months after Imatinib treatment in predicting treatment responses at 6 months and 12 months Methods: Institution based prospective observational study involving 94 newly diagnosed CML‐CP patients who attended the outpatient department of Clinical Hematology at IHTM between Jan,2015 to Dec,2016. Patients who were intolerant or non‐compliant with therapy, response assessment and who failed hematologic response at 3 months were excluded from the study. Cytogenetics were assessed by FISH performed on bone marrow aspirate samples and molecular responses were assessed by real time quantitative PCR Results: 51% and 70.2% of our study patients achieved CCyR at 6 and 12 months respectively. The rates of failure of cytogenetic response were 13% and 20% at 6 and 12 months respectively. This observation was comparatively higher than previous studies in the West. The failure rates at 6 months were statistically significant for the patients who failed to achieve optimal molecular response at 3 months. The major molecular response, warning molecular response and failure of molecular response at 6 and 12 months in our group of patients were found to be 15%, 25%, 9%, and 34%, 39%, 27% respectively. The analyses were strongly skewed against the patients who failed to achieve optimal molecular response at 3 months, with statistical significance of p = 0.0055 for failure of molecular response at 12 months. When the comparison of these two groups of patients were made for overall response, the findings were statistically significant for failure of therapy at 12 months (p = 0.006). During follow up beyond 12 months, in the suboptimal response group, there was progression of disease in 3 including 1 death. All patients in optimal response group at 3 months were in chronic phase when last followed Summary/Conclusion: Patients in our study were around 15years younger than the patients of western studies. The cytogenetic and molecular responses to Imatinib were inferior in our patients than that observed in the western studies. Higher prevalence of bone marrow fibrosis and splenomegaly in our patients lead to different disease kinetics and therapy outcome and hence comparison with western results may not be appropriate. The molecular response at 3 months was found to be a robust indicator of responses at later time points, failure of therapy, and eventual progression of disease.