Treatment Patterns and Associated Outcomes in Chronic Phase CML Patients Who Fail Imatinib 400 Mg Daily
Authors: Scott Jessica M. , Mauro Michael J. 
Published: October 2019

Abstract 4436

INTRODUCTION:
For chronic phase (CP-CML) patients failing standard dose (SD) imatinib (400 mg daily) several options remain including higher dose imatinib (600 or 800 mg daily) or switch to another tyrosine kinase inhibitor (TKI). Less often referral for stem cell transplantation or switch to novel therapies via clinical trial options is pursued. There may be differences in response and outcome between patients treated with high dose imatinib, dasatinib, nilotinib, or other therapy following failure of SD imatinib, and those differences may be correlated with the reasons for SD imatinib failure.

PURPOSE:
This analysis will evaluate the treatment patterns and associated outcomes for patients with chronic myeloid leukemia in CP-CML who failed imatinib 400 mg daily, and analyze potential correlation with the reasons for discontinuation of SD imatinib.

METHODS:
A 50-patient medical chart review commenced in June 2011 to identify CP-CML patients who received another intervention after failing treatment with SD imatinib. Retrospective adult (≥18 years) subjects were identified who: 1) had been diagnosed with Philadelphia chromosome positive CML in chronic phase, 2) had received imatinib prior to any other TKI, 3) had failed treatment with the standard dose of 400mg daily due to resistance, intolerance, disease progression to accelerated phase (AP) or blast crisis (BC), or inadequate response 4) failed standard dose imatinib after FDA approval of dasatinib and nilotinib for second line use (after Nov 2007) and 5) are followed at the study site (+/− additional community physician management). Retrospective data pertaining to CML diagnosis and imatinib treatment was collected with a goal of 12-month minimum prospective review from time of SD imatinib failure, with a maximal duration of follow-up planned of 4 years post SD imatinib failure. Reasons for failure and subsequent treatment patterns, outcomes were evaluated and descriptive statistical analysis planned. No intervention was involved in this study.

RESULTS:
To date, chart review has yielded 38 patients who ranged in age from 15 to 70 years of age (mean 45 years) at time of diagnosis. They were 55% male, 45% female and were predominantly white (84%). Sokal score was recorded in 55% of the population and was evenly distributed where recorded (high n=8, intermediate n=6, low n=7). None of the patients progressed to AP or BC during treatment with SD imatinib. Treatment failures were due to inadequate response (40%), resistance (26%), or intolerance (34%). All participants were treated with a TKI as the next intervention following SD imatinib failure, as outlined in Table 1. Of the patients who failed imatinib due to inadequate response, the majority (73%) received high dose imatinib; of those who failed due to resistance a majority received dasatinib (60%) and of those who failed due to intolerance a majority received nilotinib (69%).

CONCLUSIONS:
Initial analysis demonstrates preference of high dose imatinib or one of the second line TKIs over others in patients who fail imatinib, based on reason for failure. High dose imatinib was more common in cases of inadequate response after SD imatinib; dasatinib was more commonly utilized in the case of SD imatinib resistance. Nilotinib was more commonly used in the case of intolerance to SD imatinib. Assessment of long-term patient outcome is ongoing, and additional cases. Further analysis will include an examination of the toxicity and efficacy of second line therapy, as well as the prognostic factors that influence treatment patterns for CP-CML patients who failed imatinib 400 mg daily.

Disclosures:
Mauro: Novartis: Research Funding; Bristol Myers Squibb: Research Funding; Ariad: Research Funding.