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

Rousselot, Philippe, Coude, Marie Magdelaine, Gokbuget, Nicola, Passerini, Carlo Gambacorti, Hayette, Sandrine, Cayuela, Jean-Michel, Huguet, Francoise, Leguay, Thibaut, Chevallier, Patrice, Salanoubat, Celia, Bonmati, Caroline, Alexis, Magda, Hunault, Mathilde, Glaisner, Sylvie, Agape, Philippe, Berthou, Christian, Jourdan, Eric, Fernandes, Jose, Sutton, Laurent, Banos, Anne, Reman, Oumedaly, Lioure, Bruno, Thomas, Xavier, Ifrah, Norbert, Lafage-Pochitaloff, Marina, Bornand, Anne, Morisset, Laure, Robin, Valerie, Pfeifer, Heike, Delannoy, Andre, Ribera, Josep, Bassan, Renato, Delord, Marc, Hoelzer, Dieter, Dombret, Herve and Ottmann, Oliver 2016. Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL. Blood 128 (6) , pp. 774-782. 10.1182/blood-2016-02-700153

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Abstract

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-ABL1T315I 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-ABL1T315I from diagnosis identified patients with at high risk of early relapse and may help to personalize therapy.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Dasatinib, a potent TKI, combined with low-intensity chemotherapy gave 36% 5-year OS in Ph+ ALL patients over the age of 55 years.
Publisher: American Society of Hematology
ISSN: 0006-4971
Date of First Compliant Deposit: 16 January 2018
Date of Acceptance: 13 April 2016
Last Modified: 17 Jan 2018 10:25
URI: http://orca-mwe.cf.ac.uk/id/eprint/96041

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