Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL
In: ISSN: 0006-4971, 2016
academicJournal
Zugriff:
International audience ; Prognosis of Philadelphia-positive (Ph(+)) acute lymphoblastic leukemia (ALL) in the elderly has improved during the imatinib era. We investigated dasatinib, another potent tyrosine kinase inhibitor, in combination with low-intensity chemotherapy. Patients older than age 55 years were included in the European Working Group on Adult ALL (EWALL) study number 01 for Ph(+) ALL (EWALL-PH-01 international study) and were treated with dasatinib 140 mg/day (100 mg/day over 70 years) with intrathecal chemotherapy, vincristine, and dexamethasone during induction. Patients in complete remission continued consolidation with dasatinib, sequentially with cytarabine, asparaginase, and methotrexate for 6 months. Maintenance therapy was dasatinib and vincristine/dexamethasone reinductions for 18 months followed by dasatinib until relapse or death. Seventy-one patients with a median age of 69 years were enrolled; 77% had a high comorbidity score. Complete remission rate was 96% and 65% of patients achieved a 3-log reduction in BCR-ABL1 transcript levels during consolidation. Only 7 patients underwent allogeneic hematopoietic stem cell transplantation. At 5 years, overall survival was 36% and up to 45% taking into account deaths unrelated to disease or treatment as competitors. Thirty-six patients relapsed, 24 were tested for mutation by Sanger sequencing, and 75% were T315I-positive. BCR-ABL1(T315I) was tested by allele-specific oligonucleotide reverse transcription-quantitative polymerase chain reaction in 43 patients and detection was associated with short-term relapses. Ten patients (23%) were positive before any therapy and 8 relapsed, all with this mutation. In conclusion, dasatinib combined with low-intensity chemotherapy was well-tolerated and gave long-term survival in 36% of elderly patients with Ph(+) ALL. Monitoring of BCR-ABL1(T315I) from diagnosis identified patients with at high risk of early relapse and may help to personalize therapy
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Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL
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| Autor/in / Beteiligte Person: | Rousselot, Philippe ; Coudé, Marie Magdelaine ; Gokbuget, Nicola ; Gambacorti Passerini, Carlo ; Hayette, Sandrine ; Cayuela, Jean-Michel ; Huguet, Françoise ; Leguay, Thibaut ; Chevallier, Patrice ; Salanoubat, Celia ; Bonmati, Caroline ; Alexis, Magda ; Hunault, Mathilde ; Glaisner, Sylvie ; Agape, Philippe ; Berthou, Christian ; Jourdan, Eric ; Fernandes, José ; Sutton, Laurent ; Banos, Anne ; Reman, Oumedaly ; Lioure, Bruno ; Thomas, Xavier ; Ifrah, Norbert ; Lafage-Pochitaloff, Marina ; Bornand, Anne ; Morisset, Laure ; Robin, Valérie ; Pfeifer, Heike ; Delannoy, Andre ; Ribera, Josep ; Bassan, Renato ; Delord, Marc ; Hoelzer, Dieter ; Dombret, Herve ; Ottmann, Oliver G. ; Le Collège d'études mondiales/FMSH ; Fondation Maison des sciences de l'homme (FMSH) ; Laboratoire Central d'Anatomie et de Cytologie Pathologiques Hôpital Edouard Herriot -, HCL ; Hôpital Edouard Herriot CHU -, HCL ; Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL) ; Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL) ; Centre Léon Bérard Lyon -Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) ; Centre Hospitalier Universitaire de Toulouse (CHU Toulouse) ; Bordeaux, CHU ; Centre d'investigation clinique en cancérologie (CI2C) ; Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes) ; Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy) ; Centre Hospitalier Régional d'Orléans (CHRO) ; Lymphocytes Boimmunité et Immunothérapies (LBAI) ; Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest ; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM) ; Université de Brest (UBO) ; Centre Hospitalier Régional Universitaire de Brest (CHRU Brest) ; Centre Hospitalier Saint Jean de Perpignan ; d'Argenteuil, Hôpital ; Hôpital de Bayonne ; Centre Hospitalier de la Côte Basque (CHCB) ; Institut d'Hématologie de Basse-Normandie (IHBN) ; Université de Caen Normandie (UNICAEN) ; Normandie Université (NU)-Normandie Université (NU)-CHU Caen ; Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse Caen (UNICANCER/CRLC) ; Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER ; Centre Hospitalier Universitaire Strasbourg (CHU Strasbourg) ; Les Hôpitaux Universitaires de Strasbourg (HUS) ; Hospices Civils de Lyon (HCL) ; Assistance Publique - Hôpitaux de Marseille (APHM) ; Institut Universitaire d'Hématologie (IUH) ; Université Paris Diderot - Paris 7 (UPD7) ; Saint-Louis, Hôpital ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7) |
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| Zeitschrift: | ISSN: 0006-4971, 2016 |
| Veröffentlichung: | HAL CCSD ; American Society of Hematology, 2016 |
| Medientyp: | academicJournal |
| DOI: | 10.1182/blood-2016-02-700153 |
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