Comparative Real-World Effectiveness of Tyrosine Kinase Inhibitors as Induction Therapy for Philadelphia-Positive Acute Lymphoblastic Leukemia: A Multicenter Retrospective Study

Author(s)

Talha Badar, MD1, Michael Heckman, BS, MS2, Yan Zhang, PhD3, Sophia Blumenfeld, BS4, Ravi Narra, MD, MS5, Emily Curran, MD6, Vamsi Kota, MBBS7, Rory Shallis, MD8, Anand Patel, BA, MD9, Anjali Advani, MD10, Neil Palmisiano, MD, MS11, Ehab Atallah, MD12, Alice Mims, MD, MSRC13, Alexander Coltoff, MD14, Cameron Hunter, MD15, Shyam A. Patel, MD, PhD16, Adam DuVall, MD, MPH17, Zulfa Omer, MD18, Omer Jamy, MD19, Brian Jonas, MD, PhD20, Charles E. Foucar, MD21, L. Evan Reddick, PhD22, Luis G. Hernandez, MPH, MSc, PhD23, Mark Litzow, MD24.
1Division of Hematology-Oncology and Bone Marrow Transplant Program, Mayo Clinic, Jacksonville, FL, USA, 2Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL, USA, 3US HEOR, Takeda Pharmaceuticals America, Inc., Lexington, MA, USA, 4Quantitative Health Science, Mayo Clinic, Jacksonville, FL, USA, 5Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA, 6Internal Medicine, Division of Hematology/Oncology, University of Cincinnati Cancer Center, Cincinnati, OH, USA, 7Hematology and Oncology, Georgia Cancer Center at WellStar MCGHealth, Augusta, GA, USA, 8Section of Medical Oncology and Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA, 9Section of Hematology-Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA, 10Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA, 11Blood Disorders, Rutgers Cancer Institute, New Brunswick, NJ, USA, 12Internal Medicine, Medical College of Wisconsin, Milwuakee, WI, USA, 13Division of Hematology, The Ohio State University, Columbus, OH, USA, 14Medicine, Division of Hematology/Oncology, Medical University of South Carolina, Charleston, SC, USA, 15Internal Medicine (Hematology), Yale School of Medicine, New Haven, CT, USA, 16Division of Hematology/Oncology, UMass Chan Medical School, Worcester, MA, USA, 17Medicine, University of Chicago Medicine, Chicago, IL, USA, 18Department of internal medicine, division of Hematology and medical oncology, University of Cincinnati, Cincinnati, OH, USA, 19Medicine, University of Alabama at Birmingham, Birmingham, AL, USA, 20Internal Medicine: Malignant Hematology/Cellular Therapy and Transplantation, University of Califonia, Davis, Sacramento, CA, USA, 21Internal Medicine, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA, 22US Medical Affairs, Takeda Pharmaceuticals Americas, Inc., Lexington, MA, USA, 23Head, Global Health Economics & US HEOR, Takeda Pharmaceuticals America, Inc., Lexington, MA, USA, 24Hematology, Mayo Clinic, Rochester, MN, USA.
OBJECTIVES: Tyrosine kinase inhibitors (TKIs) have significantly improved treatment outcomes in Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). The only global, registrational head-to-head clinical trial in newly diagnosed Ph+ ALL is PhALLCON (NCT03589326) comparing ponatinib and imatinib in combination with low-dose chemotherapy. This current study aimed to compare three TKIs dasatinib, imatinib, and ponatinib, as the induction therapy for Ph+ ALL in the real world.
METHODS: This was a retrospective cohort study with medical record data extraction from 15 academic institutions in the US. Eligible patients were adults diagnosed with Ph+ ALL who received either dasatinib, imatinib, or ponatinib as induction treatment between January-2013 and May-2024. Kaplan-Meier (KM) analysis was conducted to estimate survival probabilities. Multivariable logistic and Cox regression models were applied, with the adjustment of baseline demographics, clinical characteristics, and allogeneic hematopoietic cell transplantation as a time-dependent covariate, to compare multiple treatment outcomes (e.g., progression-free survival [PFS], minimal residual disease negativity [MRD-] post induction).
RESULTS: A total of 435 patients (dasatinib: 300; imatinib: 53; ponatinib: 82) were included in this study. For dasatinib, imatinib, and ponatinib, 36-month KM estimates for overall survival were 68.2%, 65.6%, and 74.1%, respectively; 36-month PFS estimates were 59.3%, 44.4%, and 65.7%, respectively. In the unadjusted analysis, ponatinib had significantly improved PFS (Hazard Ratio [HR]: 0.50; p = 0.013) and MRD- (Odds Ratio [OR]: 2.57; p = 0.032) over imatinib, and improved outcomes over dasatinib, although not statistically significant (PFS — HR: 0.77; p = 0.24; MRD- — OR: 1.15; p = 0.60). In the multivariable analysis, ponatinib had significantly better PFS than imatinib (HR: 0.53; p = 0.028) and better PFS than dasatinib, although not statistically significant (HR = 0.81; p = 0.37).
CONCLUSIONS: For induction treatment of Ph+ ALL, ponatinib was associated with statistically significant improved clinical outcomes over imatinib and numerically better outcomes compared to dasatinib.

Conference/Value in Health Info

2025-11, ISPOR Europe 2025, Glasgow, Scotland

Value in Health, Volume 28, Issue S2

Code

CO60

Topic

Clinical Outcomes

Topic Subcategory

Comparative Effectiveness or Efficacy

Disease

Oncology

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