Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL
Mené sur 71 patients atteints d'une leucémie lymphoblastique aiguë Ph+ (âge médian : 69 ans), cet essai évalue l'efficacité et la toxicité d'un traitement d'entretien combinant le dasatinib et une chimiothérapie de faible intensité à base de vincristine et dexaméthasone
Dasatinib, a potent TKI, combined with low-intensity chemotherapy gave 36% 5-year OS in Ph+ ALL patients over the age of 55 years.Prospective monitoring of mutations may be useful to personalize therapy in Ph+ ALL patients not eligible for intensive therapies. Prognosis of Philadelphia-positive 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 55 years were included in the 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, reduced doses of sequential cytarabine and methotrexate for 6 months. Maintenance therapy was dasatinib and vincristine/dexamethasone re-inductions 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 3log reduction in BCR-ABL1 transcript levels during consolidation. Only seven 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 ASO RT-QPCR in 43 patients and detection was associated with short-term relapses. Ten patients (23%) were positive before any therapy and eight 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 switch therapy.
Blood 2016