Ponatinib Increased Overall Survival in Patients with Chronic-Phase CML

A study published in Cancer found that treatment with ponatinib significantly improved overall survival (OS) for patients with chronic-phase chronic myeloid leukemia (CP-CML) and T315I mutation, compared with hematopoietic cell transplantation (HCT).

The study analyzed data from the multicenter, international, open-label, single-arm, phase II PACE trial and the European Bone Marrow Transplant (EBMT) registry. Patients included in the analysis had either CML or Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL), and all patients were T315I-positive.

The authors compared outcomes between 128 patients from the PACE trial who received ponatinib and 56 patients from the EBMT registry who underwent HCT. Patients had the following diagnoses:

  • CP-CML: 64 patients received ponatinib and 26 received HCT
  • accelerated-phase CML (AP-CML): 8 patients received ponatinib and 8 patients received HCT
  • blast crisis CML (BC-CML): 24 patients received ponatinib and 17 received HCT
  • Ph+ ALL: 22 received ponatinib and 5 received HCT

At follow-up of 24 and 48 months, patients with CP-CML had higher rates of OS, compared with the HCT group (24 months: 84% vs. 60.5%; p=0.004; 48 months: 72.7% vs. 55.8%; p=0.013). However, in the AP-CML cohort, rates of OS at 24 months and 48 months did not differ significantly between ponatinib – and HCT-treated patients (24 months: 77.2% vs. 68.8%; p=0.618; 48 months: 69% vs. 68.8%; p=0.889).

Also, in the BC-CML and PH+ALL cohorts, ponatinib treatment was associated with lower rates of OS, compared with HCT:

  • BC-CML: 24-month OS = 13.9% vs. 36.3% (p=0.084); 48-month OS = 2% vs. 26% (p=0.026)
  • Ph+ ALL: 24-month OS = 8.8% vs. 70.3% (p=0.059); 48-month OS = 8.8% vs 32% (p=0.119)

Limitations of the study include the small sample samples sizes in each stratum, residual confounding variables, potential selection bias, and missing data in the EBMT database.

Source: Nicolini F, Basak G, Kim D, et al. Overall survival with ponatinib versus allogeneic stem cell transplantation in Philadelphia chromosome-positive leukemias with the T315I mutation. Cancer. 2017 April 7. [Epub ahead of print]