A sequential approach with imatinib, chemotherapy and transplant for adult Ph+ acute lymphoblastic leukemia. Final results of the GIMEMA LAL 0904 study

In the GIMEMA LAL 0904 protocol, adult Ph+ acute lymphoblastic leukemia patients were treated with chemotherapy for induction and consolidation, followed by maintenance with imatinib. The protocol was subsequently amended and imatinib was incorporated in the induction and post-remission phase together with chemotherapy. Due to the toxicity of this combined approach, the protocol was further amended to a sequential scheme based on imatinib plus steroids as induction, followed by consolidation with chemotherapy plus imatinib and, when applicable, by a hematopoietic stem cell transplant. Fifty-one patients (median age: 45.9 years) were enrolled in the final sequential protocol, hereby reported. At the end of induction (day +50), 96% of evaluable patients (n=49) achieved a complete hematologic remission; after consolidation, all were in complete hematologic remission. No deaths in induction were recorded. Overall survival and disease-free survival at 60 months are 48.8% and 45.8%, respectively. At day +50 (end of the imatinib induction), a log-reduction of BCR-ABL1 levels >1.3 was associated with a significantly more prolonged disease-free survival (55.6%, C.I. 95%: 39.0-79.3 vs 20%, C.I. 95%: 5.8-69.1; p=0.03), overall survival (59.1%, C.I. 95%: 42.3-82.6 vs 20%, C.I. 95%: 5.8-69.1, p=0.02) and lower relapse incidence (20.5%, C.I. 95%: 7.2-38.6 vs 60.0%, C.I. 95%: 21.6-84.3, p=0.01). Mean BCR-ABL1 levels remained significantly higher in patients who subsequently relapsed. Finally, BCR-ABL1p190 patients showed a significantly faster molecular response than BCR-ABL1p210 patients (p=0.023). Thought the study was not powered to evaluate the role of allogeneic stem cell transplant, allografting positively impacted on overall survival and disease-free survival. A sequential approach with imatinib alone in induction, consolidated by chemotherapy plus imatinib followed by a stem cell transplant is a feasible, well-tolerated and effective strategy for adult Ph+ acute lymphoblastic leukemia, leading to the best long-term survival rates so far reported. Trial ID: NCT00458848