Ponatinib vs Allogeneic SCT Promising for T315I Mutation-positive CP-CML
Ponatinib was associated with significantly longer overall survival than allogeneic stem cell transplantation in patients with chronic myeloid leukemia.
Ponatinib was associated with significantly longer overall survival than allogeneic stem cell transplantation (alloSCT) in patients with chronic myeloid leukemia in chronic phase (CP-CML) that harbor the T315I mutation.1
AlloSCT is considered standard treatment for patients with accelerated or blast phase CML, de novo Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), or patients with CP-CML who are resistant or intolerant to at least 2 tyrosine kinase inhibitors (TKIs). Ponatinib is indicated for the treatment of patients with CML or Ph+ ALL who have a positive BCR-ABL1 T315I mutation or for when there is no other suitable TKI available. Therefore, ponatinib currently represents a suitable alternative to alloSCT in patients harboring a T315I mutation, but outcomes between patients treated with these 2 approaches have not been compared.
For the study, researchers pooled data from the phase 2 PACE trial and the European Bone Marrow Transplant registry to indirectly compare the 2 treatment strategies. A total of 128 patients who received ponatinib and 56 who underwent alloSCT were included.
Results showed that among patients with CP-CML, median overall survival had not been reached in the ponatinib group and was 103.3 months in the alloSCT group (HR, 0.37; 95% CI, 0.16 - 0.84; P = .017). In contrast, there was no significant difference in median overall survival between the 2 treatment groups in patients with CML in accelerated phase (HR, 0.90; 95% CI, 0.20 - 4.10; P = .889) and was significantly shorter in those in blast phase who had received ponatinib vs alloSCT (HR, 2.29; 95% CI, 1.08 - 4.82; P = .030).
In regard to patients with Ph+ ALL, those treated with ponatinib had nominally shorter median overall survival compared with those who had received alloSCT (HR, 2.77; 95% CI, 0.73 - 10.56; P = .136).
Although follow-up remains short to date, ponatinib could represent a promising therapeutic alternative in this setting.
- Nicolini FE, Basak GW, Kim D-W, et al. The impact of ponatinib versus allogeneic stem cell transplant (SCT) on outcomes in patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with the T315I mutation [abstract]. https://ash.confex.com/ash/2015/webprogram/Paper84244.html. Updated December 7, 2015. Accessed January 11, 2016.