Dasatinib and dexamethasone followed by hematopoietic cell transplantation for adults with Ph-positive ALL
| Autor: | Jonathan E. Kolitz, Susan M. Christner, Michaela Liedtke, Richard Stone, Geoffrey L. Uy, Meir Wetzler, Jan H. Beumer, Lionel D. Lewis, Jun Yin, Matthew J Wieduwilt, Wendy Stock, Elizabeth Storrick, Richard A. Larson, Steven M. Devine, Ryan J. Mattison, Bayard L. Powell |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Oncology
Adult medicine.medical_specialty Clinical Trials and Observations medicine.medical_treatment Dasatinib Ph Positive Dexamethasone Median follow-up Internal medicine hemic and lymphatic diseases medicine Humans Philadelphia Chromosome Chemotherapy Hematopoietic cell business.industry Hematopoietic Stem Cell Transplantation Hematology Middle Aged Precursor Cell Lymphoblastic Leukemia-Lymphoma Transplantation Methotrexate business medicine.drug |
| Zdroj: | Blood Advances |
| ISSN: | 2473-9537 |
| Popis: | Key Points Dasatinib and dexamethasone induction then allogeneic hematopoietic cell transplantation was feasible and effective for untreated Ph+ ALL.Treatment failure was associated with BCR-ABL1 T315I mutation, the p210 BCR-ABL1 isoform, or isolated CNS relapse. Visual 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. |
| Databáze: | OpenAIRE |
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