Anjali S Advani1, Anna Moseley2,3, Kristen M O'Dwyer4, Brent L Wood5,6, Min Fang7, Matthew J Wieduwilt8,9, Ibrahim Aldoss10, Jae H Park11, Rebecca B Klisovic12, Maria R Baer13, Wendy Stock14, Rupali R Bhave15, Megan Othus2,3, Richard C Harvey16, Cheryl L Willman16, Mark R Litzow17, Richard M Stone18, Elad Sharon19, Harry P Erba20. 1. Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH. 2. SWOG Statistics and Data Management Center, Seattle, WA. 3. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA. 4. Department of Medicine, Hematology/Oncology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, MN. 5. Department of Laboratory Medicine, University of Washington, Seattle, WA. 6. Current address: Department of Hematopathology, Children's Hospital of Los Angeles, CA. 7. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA. 8. Division of Hematology/Oncology, University of California San Diego Moores Cancer Center, La Jolla, CA. 9. Current address: Department of Medicine, University of Oklahoma, Oklahoma City, OK. 10. Department of Hematology & Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA. 11. Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, NY. 12. Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, GA. 13. Department of Medicine, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD. 14. Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL. 15. Division of Medical Oncology and Hematology, Wake Forest School of Medicine, Winston Salem, NC. 16. Department of Pathology, University of New Mexico, Albuquerque, NM. 17. Division of Hematology, Mayo Clinic, Rochester, MN. 18. Department of Medicine, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA. 19. Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD. 20. Division of Hematologic Malignancies and Cellular Therapy, Duke University Cancer Institute, Durham, NC.
Abstract
PURPOSE: Chemotherapy outcomes in older patients with Philadelphia (Ph) chromosome-negative B-acute lymphoblastic leukemia (ALL) are very poor. Here, we evaluated blinatumomab as induction and consolidation therapy followed by prednisone, vincristine, 6-mercaptopurine, and methotrexate (POMP) maintenance chemotherapy in this patient population. PATIENTS AND METHODS: Patients were treated at National Clinical Trial Network sites. Eligibility criteria included age ≥ 65 years and newly diagnosed Ph chromosome-negative B-ALL. Patients received blinatumomab as induction for one-two cycles until attainment of response (complete remission (CR) and CR with incomplete count recovery). Patients then received three cycles of consolidation with blinatumomab followed by 18 months of POMP maintenance chemotherapy. Eight doses of intrathecal methotrexate were administered as central nervous system prophylaxis. RESULTS: Twenty-nine eligible patients were enrolled. The median age was 75 years, and the median bone marrow blast count at diagnosis was 87%. Cytogenetic risk was poor in 10 patients (34%), and five of 14 patients (36%) tested had the Ph-like ALL gene signature. Nineteen patients (66%; 95% CI, 46 to 82) achieved CR. Kaplan-Meier 3-year disease-free survival and overall survival estimates were 37% (95% CI, 17 to 57) and 37% (95% CI, 20 to 55), respectively. CONCLUSION: Blinatumomab was well tolerated and effective in the treatment of older patients with newly diagnosed Ph chromosome-negative B-ALL, including patients with poor-risk cytogenetics. The 3-year disease-free survival and overall survival results are encouraging and suggest that this approach should be further explored.
PURPOSE: Chemotherapy outcomes in older patients with Philadelphia (Ph) chromosome-negative B-acute lymphoblastic leukemia (ALL) are very poor. Here, we evaluated blinatumomab as induction and consolidation therapy followed by prednisone, vincristine, 6-mercaptopurine, and methotrexate (POMP) maintenance chemotherapy in this patient population. PATIENTS AND METHODS: Patients were treated at National Clinical Trial Network sites. Eligibility criteria included age ≥ 65 years and newly diagnosed Ph chromosome-negative B-ALL. Patients received blinatumomab as induction for one-two cycles until attainment of response (complete remission (CR) and CR with incomplete count recovery). Patients then received three cycles of consolidation with blinatumomab followed by 18 months of POMP maintenance chemotherapy. Eight doses of intrathecal methotrexate were administered as central nervous system prophylaxis. RESULTS: Twenty-nine eligible patients were enrolled. The median age was 75 years, and the median bone marrow blast count at diagnosis was 87%. Cytogenetic risk was poor in 10 patients (34%), and five of 14 patients (36%) tested had the Ph-like ALL gene signature. Nineteen patients (66%; 95% CI, 46 to 82) achieved CR. Kaplan-Meier 3-year disease-free survival and overall survival estimates were 37% (95% CI, 17 to 57) and 37% (95% CI, 20 to 55), respectively. CONCLUSION: Blinatumomab was well tolerated and effective in the treatment of older patients with newly diagnosed Ph chromosome-negative B-ALL, including patients with poor-risk cytogenetics. The 3-year disease-free survival and overall survival results are encouraging and suggest that this approach should be further explored.
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