Treatment efficacy of ponatinib as salvage therapy in relapse chronic myeloid leukemia with T315I mutation after allogeneic stem cell transplantation: report of 12 cases / 中华器官移植杂志

ABSTRACT

Objective To analyze the efficacy of ponatinib as salvage therapy in relapse chronic myeloid leukemia with T315I mutation (CML-T315D after allogeneic stem cell transplantation (allo-HSCT).Methods Twelve patients with CML-T315I (10 cases of T315I mutation before transplantation and 2 cases of T315I mutation at the time of relapse after transplantation) were included in this retrospective analysis.Ponatinib was used as single agent or combined with chemotherapy and/or donor lymphocyte infusion.The samples obtained for RTQ-PCR were also analyzed for the BCR ABL1 mutation by direct sequencing.Scanning of the ABL KD (amino acids 219-506) for the presence of mutations was sequenced by Sanger.Results In 12 patients with relapse after transplantation,2 patients with molecular relapse were treated with only single-agent ponatinib,and among 10 patients with hematologic relapse,1 patient was treated with single-agent ponatinib and 3 patients were given ponatinib combined with donor lymphocyte infusion (DLI),the remaining 6 patients were treated with ponatinib combined with chemotherapy and DLI.After the treatment with ponatinib,11 patients had a good response,10 patients obtained complete hematologic remission (CHR),1 patient obtained partial hematologic remission (PHR) and 1 patient had no response (NR).For cytogenetic response,10 patients obtained complete cytogenetic response (CCyR),1 patient obtained partial cytogenetic response (PCyR) and one patient had no cytogenetic response.For the molecular biological response,9 patients obtained complete molecular response (CMR),1 patient obtained majore molecular response (MMR) and 2 patients had no molecular biological response.The median time to obtain CHR was 36 days (29-96 days),the median time to obtain CCyR was 63 days (32-127 days),and the median time to obtain CMR was 89 days (27-152 days).The median follow-up time after treatment with ponatinib was 598 (range,93-1470) days,9 patients survived and 3 died.Causes of deaths included leukemia relapse (n =2)and ineffective treatment (n =1).The 2-year overall and disease-free survival rate after relapse in 12 patients was 75.0％ ± 12.5％ and 31.7％ ± 14.9％,respectively.Conclusion This small sample data suggested that ponatinib as salvage therapy had a good response to the relapse CML-T315I after allo-HSCT.