Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Therapy: Poster III
Bosutinib (BOS), a Src/Abl tyrosine kinase inhibitor (TKI), is approved for adults with Philadelphia chromosome-positive (Ph+) CML that is resistant/intolerant to prior therapy. In this retrospective analysis, baseline and on-treatment characteristics of chronic phase (CP) CML pts receiving second-line BOS following imatinib resistance (IM-R) or intolerance (IM-I) in an ongoing open-label, phase 1/2 study and a long-term extension study were examined to identify potential predictors of duration of major cytogenetic response (MCyR), overall survival (OS), and progression-free survival (PFS), using a backward-elimination multivariate Cox regression model.
A total of 284 (IM-R, n=195; IM-I, n=89) pts who received BOS starting at 500 mg/d were included in this analysis. Median (range) age was 53 (18‒91) y; time from CML diagnosis was 3.7 (0.1‒15.1) y; treatment duration was 25.6 (0.2‒106.7) mo; follow-up duration was 53.7 (0.5‒106.8) mo. For the last enrolled patient, time from first BOS dose was ≥6 y.
After ≥6 y of follow-up, median MCyR duration and OS were not yet reached. Kaplan-Meier estimated probability of maintaining MCyR at 6 y was 71%, OS rate was 83%, and cumulative incidence of on-treatment disease progression or death was 21%. Several factors were identified as predictive of MCyR duration, OS or PFS, including baseline Ph+ ratio ≥95% vs ≤35% and MCyR by week 12, which were significant predictors of all 3. Other significant predictors of decreased OS included: age ≥65, BOS-sensitive mutations vs no mutations and higher peripheral blood (PB) blasts at baseline (all P≤0.031; Table). Other significant predictors of decreased PFS included: higher PB blasts and no dose reduction to 400 mg/d due to AEs (all P≤0.025; Table). Prior IM response or resistance did not predict long-term outcomes, nor did any treatment-emergent adverse events examined except for abnormal liver function test (LFT), which was predictive of increased OS.
In conclusion, pts with CP CML resistant/intolerant to IM treated with BOS were identified as having an increased risk of poorer outcomes if they had the following characteristics: baseline Ph+ ratio ≥95% vs ≤35%, higher PB blasts at baseline or no MCyR by week 12. Having a better understanding of factors that may be predictive of long-term patient outcomes with TKI therapies may aid healthcare providers in the future selection of optimal treatment regimens for pts with Ph+ CML.
Disclosures: Cortes: ARIAD Pharmaceuticals Inc.: Consultancy , Research Funding ; BMS: Consultancy , Research Funding ; Novartis: Consultancy , Research Funding ; Teva: Consultancy , Research Funding ; Pfizer: Consultancy , Research Funding . Brümmendorf: Ariad: Consultancy , Honoraria ; Novartis: Consultancy , Honoraria , Research Funding ; Pfizer: Consultancy , Honoraria ; Bristol-Myers Squibb: Consultancy , Honoraria ; Patent: Patents & Royalties: Patent on the use of imatinib and hypusination inhibitors . Kim: BMS: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees , Research Funding ; Novartis: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees , Research Funding ; Pfizer: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees , Research Funding ; ILYANG: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees , Research Funding . Schafhausen: ARIAD: Consultancy , Honoraria ; Pfizer: Consultancy , Honoraria ; BMS: Consultancy , Honoraria ; Novartis: Consultancy , Honoraria . Nadanaciva: Pfizer Inc: Employment . Bardy-Bouxin: Pfizer Inc: Employment . Shapiro: Pfizer Inc: Employment , Other: Stock Ownership . Leip: Pfizer Inc: Employment . Lipton: Ariad: Equity Ownership , Honoraria , Membership on an entity’s Board of Directors or advisory committees , Research Funding , Speakers Bureau ; BMS: Honoraria , Membership on an entity’s Board of Directors or advisory committees , Research Funding , Speakers Bureau ; Novartis: Honoraria , Membership on an entity’s Board of Directors or advisory committees , Research Funding , Speakers Bureau ; Pfizer: Honoraria , Membership on an entity’s Board of Directors or advisory committees , Research Funding , Speakers Bureau . Gambacorti-Passerini: Pfizer: Consultancy , Research Funding ; BMS: Consultancy .
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