Overall survival with ponatinib versus allogeneic stem cell transplantation in Philadelphia chromosome-positive leukemias with the T315I mutation.

Effective treatment options for patients with chronic myeloid leukemia (CML) or Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) who have the threonine to isoleucine mutation at codon 315 (T315I) are few. The objective of this study was to compare overall survival (OS) between patients with CML and those with Ph+ ALL who received treatment with ponatinib versus allogeneic stem cell transplantation (allo-SCT). A post hoc, retrospective, indirect comparison of OS among patients who received single-agent ponatinib in the Ponatinib Ph+ ALL and CML Evaluation (PACE) trial with those who underwent allo-SCT as reported to the European Bone Marrow Transplant registry, stratified by CML disease phase and Ph+ ALL, was conducted. Kaplan-Meier survival curves and multivariate Cox proportional-hazards models were used to compare OS between intervention groups, adjusting for time from diagnosis to intervention, age, sex, and geographic region; 24-month and 48-month OS rates and median OS were reported. After adjustment for potential confounders, 24-month and 48-month OS rates were significantly higher in patients with chronic-phase CML (CP-CML) who received ponatinib compared with those who underwent allo-SCT (24 months: 84% vs 60.5%, respectively; P = .004; 48 months: 72.7% vs 55.8%, respectively; P = .013), with a hazard ratio (HR) of 0.37 (95% confidence interval [CI], 0.16-0.84; P = .017). In patients who had accelerated-phase CML, OS rates were not significantly different between the groups (HR, 0.90; 95% CI, 0.20-4.10; P = .889). In patients who had blast-crisis CML and those with Ph+ ALL, ponatinib was associated with shorter OS compared with allo-SCT (blast-crisis CML: HR, 2.29 [95% CI, 1.08-4.82; P = .030]; Ph+ ALL: HR, 2.77 [95% CI, 0.73-10.56; P = .146]). Although allo-SCT remains an important treatment option for patients with T315I-positive advanced CML and Ph+ ALL, ponatinib represents a valuable alternative for patients with T315I-positive CP-CML. Cancer 2017;123:2875-80. © 2017 American Cancer Society.

Nicolini FE ，Basak GW ，Kim DW ，Olavarria E ，Pinilla-Ibarz J ，Apperley JF ，Hughes T ，Niederwieser D ，Mauro MJ ，Chuah C ，Hochhaus A ，Martinelli G ，DerSarkissian M ，Duh MS ，McGarry LJ ，Kantarjian HM ，Cortes JE ... -  《-》

Ponatinib: A new tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia.

Shamroe CL ，Comeau JM 《-》

Clinical outcomes in patients with Philadelphia chromosome-positive leukemia treated with ponatinib in routine clinical practice-data from a Belgian registry.

Devos T ，Havelange V ，Theunissen K ，Meers S ，Benghiat FS ，Gadisseur A ，Vanstraelen G ，Vellemans H ，Bailly B ，Granacher N ，Lewalle P ，De Becker A ，Van Eygen K ，Janssen M ，Triffet A ，Vrelust I ，Deeren D ，Mazure D ，Bekaert J ，Beck M ，Selleslag D ... -  《-》

Ponatinib therapy in recurrent Philadelphia chromosome-positive central nervous system leukemia with T315I mutation after Allo-HSCT.

Central nervous system leukemia (CNSL) relapse is relatively common among Philadelphia chromosome-positive (Ph+) leukemia patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). The prognosis of patients is dismal for those with a BCR-ABL T315I mutation, which is resistant to TKIs including second-generation drugs. We assessed ponatinib for nine patients with recurrent Ph+ CNSL and a T315I mutation after allo-HSCT, including five patients with Ph+ acute lymphoblastic leukemia and four with chronic myelogenous leukemia. Five patients experienced isolated CNSL relapse, and four experienced CNSL with hematologic relapse. All patients received ponatinib combined with intrathecal chemotherapy, and four patients with hematologic relapse received systemic chemotherapy and/or donor lymphocyte infusion. All patients achieved a deep molecular response and central nervous system remission (CNSR) at a median time of 1.5 (range: 0.7-3) months after ponatinib treatment. Two patients experienced a second CNSL relapse due to ponatinib reduction, but they achieved CNSR again after an increase to the standard dosage. Six patients developed graft versus host disease. By April 1, 2019, eight patients were alive, and one died of pneumonia. The median time of survival after the first CNSL relapse posttransplantation was 18 (range: 11.2-48.5) months. Our data from a small number of samples suggests that ponatinib is effective for recurrent Ph+ CNSL patients with a BCR-ABL T315I mutation after allo-HSCT and warrants broader clinical evaluation.

He JB ，Zhang X ，Guo ZW ，Liu MM ，Xu N ，Huang F ，Fan ZP ，Xuan L ，Deng L ，Lin SH ，Xu J ，Sun J ，Liu QF ... -  《-》

Ponatinib: a review of its use in adults with chronic myeloid leukaemia or Philadelphia chromosome-positive acute lymphoblastic leukaemia.

Hoy SM 《-》