Dasatinib and dexamethasone followed by hematopoietic cell transplantation for adults with Ph-positive ALL

Author:

Wieduwilt Matthew J.1,Yin Jun2,Wetzler Meir3,Uy Geoffrey L.4,Powell Bayard L.5,Kolitz Jonathan E.6,Liedtke Michaela7ORCID,Stock Wendy8,Beumer Jan H.9ORCID,Mattison Ryan J.10,Storrick Elizabeth2,Christner Susan M.9,Lewis Lionel D.11,Devine Steven12,Stone Richard M.13,Larson Richard A.8ORCID

Affiliation:

1. University of Oklahoma, Stephenson Cancer Center, Oklahoma City, OK;

2. Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN;

3. Roswell Park Comprehensive Cancer Center, Buffalo, NY;

4. Washington University School of Medicine, Saint Louis, MO;

5. Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC;

6. Monter Cancer Center, Zucker School of Medicine at Hofstra/Northwell, Lake Success, NY;

7. Stanford University Cancer Center, Stanford, CA;

8. University of Chicago Comprehensive Cancer Center, Chicago, IL;

9. University of Pittsburgh, Pittsburgh, PA;

10. University of Wisconsin Carbone Cancer Center, Madison, WI;

11. Norris Cotton Cancer Center, The Geisel School of Medicine at Dartmouth and The Dartmouth-Hitchcock Medical Center, Lebanon, NH;

12. The Ohio State University, Columbus, OH; and

13. Dana-Farber/Partners CancerCare, Boston, MA

Abstract

Abstract Post-remission strategies after dasatinib-corticosteroid induction in adult Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL) are not well studied. We evaluated dasatinib and dexamethasone induction then protocol-defined post-remission therapies, including hematopoietic cell transplantation (HCT). Adults (N = 65) with Ph-positive ALL received dasatinib-dexamethasone induction, methotrexate-based central nervous system (CNS) prophylaxis, reduced-intensity conditioning (RIC) allogeneic HCT, autologous HCT, or chemotherapy alone, and dasatinib-based maintenance. Key end points were disease-free survival (DFS) and overall survival (OS). The median age was 60 years (range, 22-87 years). The complete remission rate was 98.5%. With a median follow-up of 59 months, 5-year DFS and OS were 37% (median, 30 months) and 48% (median, 56 months), respectively. For patients receiving RIC allogeneic HCT, autologous HCT, or chemotherapy, 5-year DFS were 49%, 29%, and 34%, and 5-year OS were 62%, 57%, and 46%, respectively. Complete molecular response rate after CNS prophylaxis was 40%. Relative to the p190 isoform, p210 had shorter DFS (median 10 vs 34 months, P = .002) and OS (median 16 months vs not reached, P = .05). Relapse occurred in 25% of allogeneic HCT, 57% of autologous HCT, and 36% of chemotherapy patients. T315I mutation was detected in 6 of 8 marrow relapses. Dasatinib CNS concentrations were low. Dasatinib-dexamethasone followed by RIC allogeneic HCT, autologous HCT, or chemotherapy was feasible and efficacious, especially with RIC allogeneic HCT. Future studies should address the major causes of failure: T315I mutation, the p210 BCR-ABL1 isoform, and CNS relapse. This study was registered at www.clinicaltrials.gov as #NCT01256398.

Publisher

American Society of Hematology

Subject

Hematology

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