P371: ponatinib as a prophylactic or pre-emptive strategy to prevent cytological relapse after allo-sct in patients with ph pos all transplanted in complete cytological remission

Background: The proper administration of TKIs after Allo-SCT in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) remains controversial and the TKI approach (prophylactic, pre-emptive or salvage) is still heterogeneous through transplant centers. In this context, very little is known about the efficacy and safety of third-generation TKIs Aims: Here we present the preliminary results of the ongoing multicentre study to analyse efficacy and safety profile of therapy with ponatinib (PONA) after Allo-SCT to prevent Ph+ ALL cytological relapse. Methods: We report the analysis of the first 48 included patients (pts) with Ph+ ALL (median age 49 years; range 20-70) who received PONA after their Allo-SCT (donors: 24 MUD, 11 siblings HLA Id and 9 Haplo and 4CB). All 48 pts received Allo-SCT while in complete cytological remission (cCR) and 26 pts (54%) had positive minimal residual disease (MRD+) before Allo-SCT. PONA was administered after Allo-SCT prophylactically (starting with MRD neg) in 26 pts or pre-emptively (starting with MRD positivity post-SCT and without hematological relapse) in 22 pts Results: The 26 pts treated prophylactically with PONA started treatment earlier, at a median of 4,3 months (range 1,5-6) after Allo-SCT, than the 22 pts treated pre-emptively, who started PONA at a median of 7,4 months (range 2-63) after Allo-SCT (p=0,01). The median starting dose of PONA was 30 mg/day (range 15-45). Reduction of the initial dose was required in 15/48 (31%) of cases (mainly in those receiving an initial dose of 45 mg/day), but a permanent discontinuation of PONA, due to toxicity, was required in only 5/48 pts (10,4%). No deaths due to PONA-related adverse events were reported. The mean and median follow-up time after Allo-SCT was 40±26 and 34 months (range 7,7-118), respectively. At last follow-up, the median duration of PONA therapy was 22 months (range 2-100). Detailed data on the safety profile of PONA were collected. In addition to PONA, 10 pts received donor lymphocyte infusions. The 5-year OS and RFS after Allo-SCT of all 48 pts were 92% and 71%, respectively (Figure 1a and 1b). The 5-year RFS after Allo-SCT of pts who received PONA as prophylaxis was 95% and it was 57% for those who received PONA pre-emptively (log-rank p=0,02). Summary/Conclusion: Preliminary data obtained from this analysis, in a homogeneous population of Ph+ ALL undergoing Allo-SCT while in CcR, although with the caution of the retrospective data, support the efficacy and safety of PONA as a maintenance strategy after Allo-SCT, resulting in a high probability of OS and DFS and in a low rate of discontinuation due to PONA-related toxicity. However, in the majority of cases where a daily dose of 45 mg was started a dose reduction to 30-15 mg/day was required, which seems to be the appropriate dose to balance efficacy and tolerability.Keywords: allo BMT, Ph+ ALL, Acute lymphoblastic leukemia