Treatment efficacy of ponatinib as salvage therapy in relapse chronic myeloid leukemia with T315I mutation after allogeneic stem cell transplantation: report of 12 cases

Abstract

Objective To analyze the efficacy of ponatinib as salvage therapy in relapse chronic myeloid leukemia with T315I mutation (CML-T315I) 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. Key words: Hematopoietic stem cell transplantation; Chronic myeloid leukemia; Relapse; T315I mutation; Ponatinib