Adult Philadelphia-Positive Acute Lymphoblastic Leukemia (Ph + ALL) Treated at Diagnosis with Imatinib Followed by 2nd Line TKI (Imatinib or Dasatinib) and Stem Cell Transplantation.

Abstract

Abstract 4109Imatinib has become an integral part of front-line therapy for Ph+ ALL, with remission rate exceeding 90% irrespective of whether Imatinib is given alone or combined with chemotherapy. Treatment outcome with Imatinib-based regimens has improved survival compared with historic controls, but most patients who do not undergo allogeneic stem cell transplantation (SCT) eventually relapse. Second generation TKI, e.g. Nilotinib and Dasatinib, show activity against most of the BCR-ABL tyrosine kinase domain mutations involved in acquired Imatinib resistance, but clinical benefit is generally short lived. In the attempt to improve the prognosis of these patients, we started a new intensive protocol consisting of induction phase with Imatinib (600 mg po, daily) in combination with conventional chemotherapy; moreover, two intrathecal methotrexate will be administered at the day +8 and +22. As known, this approach will determine an high number of complete hematologycal (CHR) and cytogenetic remissions (CcyR). Soon after, Imatinib will be discontinued and a 2nd TKI (Nilotinib or Dasatinib) will be offered to the patients. The idea is to reduce/eliminate as soon as possible the mutations generating under Imatinib. The primary objective of the study will be to assess the activity of sequential TKI to induce molecular remission; secondary objectives will be DFS, relapse rate, OS. This protocol will be designed for patients >18 years. Recruitment started in June 2008. Minimal residual disease will be investigate by RQ-PCR at day +30, +60, +90, +120, +150 and so on. The protocol has been designed for 20 patients. Three evaluable patients entered until now this trial; the median age was 47 years (range, 39-64 years). All 3 patients achieved CHR and CCyR at a median of 26 days (range, 18-31 days) and 46 days (range, 39-59 days), respectively. Monitoring RQ-PCR, a marked clearance of leukemic cells was found at d+60; when CCyR was achieve, Imatinib was discontinued and 2nd TKI was started: 2 patients received Dasatinib 100 mg po daily and 1 patient Nilotinib 800 mg po twice daily. Between d+100 and d+120, RQ-PCR became negative in the peripheral blood of all patients. One patient with an HLA+ sibling donor is waiting to receive an allograft; the other 2 patients, who did not find an HLA+ donor, received an autograft with molecular negative PBPC. The conditioning regimen consisted of the BU-Cy regimen. Both patients are alive and in CMR at 3 and 10 months after autografting. More patients and more time will confirm the efficacy of this new approach. Disclosures:No relevant conflicts of interest to declare.