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Article Dans Une Revue Blood Année : 2016

Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL

Marie Magdelaine Coudé
  • Fonction : Auteur
Nicola Gokbuget
  • Fonction : Auteur
Carlo Gambacorti Passerini
  • Fonction : Auteur
Thibaut Leguay
  • Fonction : Auteur
Celia Salanoubat
  • Fonction : Auteur
Sylvie Glaisner
  • Fonction : Auteur
Philippe Agape
  • Fonction : Auteur
José Fernandes
  • Fonction : Auteur
Anne Banos
  • Fonction : Auteur
Norbert Ifrah
  • Fonction : Auteur
Anne Bornand
  • Fonction : Auteur
Laure Morisset
  • Fonction : Auteur
Valérie Robin
  • Fonction : Auteur
Heike Pfeifer
  • Fonction : Auteur
Andre Delannoy
  • Fonction : Auteur
Josep Ribera
  • Fonction : Auteur
Renato Bassan
  • Fonction : Auteur
Dieter Hoelzer
  • Fonction : Auteur
Oliver G. Ottmann
  • Fonction : Auteur

Résumé

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

Dates et versions

hal-01800020 , version 1 (25-05-2018)

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Citer

Philippe Rousselot, Marie Magdelaine Coudé, Nicola Gokbuget, Carlo Gambacorti Passerini, Sandrine Hayette, et al.. Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL. Blood, 2016, 128 (6), pp.774-782. ⟨10.1182/blood-2016-02-700153⟩. ⟨hal-01800020⟩
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