Ponatinib Extends Survival Over Transplant in Chronic Phase CML

Treatment with ponatinib yielded better overall survival compared with allogeneic stem cell transplantation (allo-SCT) in patients with chronic phase chronic myeloid leukemia (CP-CML) with a T315I mutation, according to a new study. The drug was no better, or worse, in blast-crisis phase (BC)-CML, or in Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL).

The T315I mutation confers resistance to most tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib, bosutinib, and nilotinib. Ponatinib is the only such agent that can treat patients with this mutation. “Before the approval of ponatinib, patients with CML and Ph+ ALL who were resistant to imatinib and harbored the T315I mutation had a poor prognosis and significantly shorter survival compared with those who did not have this mutation,” wrote study authors led by Franck E. Nicolini, MD, PhD, of Medical Research Lyon Cancer Center in France. Allo-SCT had been standard therapy for these patients, and little research had compared it to ponatinib in T315I-positive patients.

The new study included patients from the PACE trial and the European Bone Marrow Transplant registry. In total, 128 patients received ponatinib and 56 underwent allo-SCT; there were 64 ponatinib and 26 allo-SCT patients in the CP-CML group; 18 and 8, respectively, in the accelerated phase (AP)-CML group; 24 and 17, respectively, in the BC-CML group; and 22 and 5, respectively with Ph+ ALL. Results were published online ahead of print in Cancer.

In the CP-CML patients, those who received ponatinib fared better than those who underwent allo-SCT. The 24-month overall survival in these patients was 84% with ponatinib and 60.5% with allo-SCT (P = .004), and at 48 months it was 72.7% and 55.8%, respectively (P = .013). The median overall survival was not reached with ponatinib, compared with 103.3 months with allo-SCT, for a hazard ratio (HR) of 0.37 (95% CI, 0.16–0.84; P = .017).

The 24-month and 48-month overall survival did not differ significantly in patients with AP-CML. The median overall survival in the AP-CML patients was not reached with ponatinib compared with 55.6 months, for an HR of 0.90 (95% CI, 0.20–4.10; P = .889). In those with BC-CML, ponatinib yielded a lower overall survival at 24 and at 48 months compared with allo-SCT; the median overall survival was 7 months with ponatinib and 10.5 months with allo-SCT, for an HR of 2.29 (95% CI, 1.08–4.82; P = .030). Similarly, those with Ph+ ALL had poorer overall survival with ponatinib, though this did not reach significance, with a median of 6.7 months vs 32.4 months with allo-SCT (95% CI, 0.73–10.56; P = .136).

“Although allo-SCT remains standard therapy for patients who have BC-CML at diagnosis or after TKI treatment, our results suggest that ponatinib alone is a valuable alternative to transplantation for prolonging survival in patients with T315I-positive CP-CML,” the authors concluded. They noted the small sample sizes in some of the subgroups in this trial, making some of the results inconclusive.