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4041 Predictors of Response Duration and Survival with Second-Line Bosutinib Therapy in Patients (pts) with Chronic Phase Chronic Myeloid Leukemia (CML) Resistant or Intolerant to Prior ImatinibClinically Relevant Abstract

Chronic Myeloid Leukemia: Therapy
Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Therapy: Poster III
Monday, December 7, 2015, 6:00 PM-8:00 PM
Hall A, Level 2 (Orange County Convention Center)

Jorge E. Cortes1, Tim H. Brümmendorf, MD2,3, Hagop M. Kantarjian, MD1, Dong-Wook Kim, MD, PhD4, Philippe Schafhausen, MD2*, Sashi Nadanaciva, D Phil5*, Nathalie Bardy-Bouxin, PhD6*, Mark Shapiro, MD7, Eric Leip, PhD7*, Jeffrey H. Lipton, MD, PhD8 and Carlo Gambacorti-Passerini, MD9

1Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
2University Cancer Center Hamburg, Hubertus Wald Tumor Center, Hamburg, Germany
3RWTH Aachen University Hospital, Aachen, Germany
4Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
5Pfizer Inc, Groton, CT
6Global Research and Development, Pfizer, Paris, France
7Pfizer Inc, Cambridge, MA
8Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada
9University of Milano-Bicocca, Monza, Italy

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 .

*signifies non-member of ASH