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

Matthew J. Wieduwilt, Jun Yin, Meir Wetzler, Geoffrey L. Uy, Bayard L. Powell, Jonathan E. Kolitz, Michaela Liedtke, Wendy Stock, Jan H. Beumer, Ryan J. Mattison, Elizabeth Storrick, Susan M. Christner, Lionel D. Lewis, Steven Devine, Richard M. Stone, Richard A. Larson

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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 5 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-basedmaintenance. Key end points were diseasefree survival (DFS) and overall survival (OS). Themedian agewas 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-yearOSwere 62%, 57%, and 46%, respectively. Completemolecular 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. T315Imutationwas detected in 6 of 8marrowrelapses. 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.

Original languageEnglish
Pages (from-to)4691-4700
Number of pages10
JournalBlood Advances
Volume5
Issue number22
DOIs
StatePublished - Nov 23 2021

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