ORLANDO, FLOverall survival was significantly longer with ponatinib than allogeneic stem cell transplant in patients with chronic phase chronic myeloid leukemia (CP-CML) who harbor the T315I mutation. The first analysis to confirm these findings was presented at the 57th American Society of Hematology (ASH) Annual Meeting.1

Ponatinib may therefore “be a promising alternative for patients with CP-CML with the T315I mutation in this setting,” said Franck E. Nicolini, MD, PhD, of Centre Hospitalier Lyon Sud in France.

Overall survival was found to be similar between intervention groups in accelerated phase CML (AP-CML) and longer for allogeneic stem cell transplant patients in blast phase CML (BP-CML) and de novo Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL).

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Ponatinib is approved in the United States and Europe for the treatment of refractory CML or de novo Ph+ ALL and those with the BCR-ABL1 T315I mutation “or for whom no other TKI therapy is indicated,” Dr. Nicolini said. “Ponatinib represents an alternative treatment option to allogeneic SCT in eligible patients harboring the T315I mutation, but differences in survival between such patients treated with ponatinib and allogeneic SCT have not been studied to date,” he added, in explaining the rationale for the study.

In this study, data from 184 patients harboring the T315I mutation from the phase 2 PACE trial of ponatinib (128 patients) and the European Bone Marrow Transplant registry (56 patients) were pooled and an indirect comparison of ponatinib and allogeneic SCT conducted. Of these patients, 90 were in CP-CML, 26 were in AP-CML, 41 were in blast phase (BP-CML), and 27 had Ph+ ALL.

Time from T315I detection to intervention was significant between the ponatinib and allogeneic SCT groups for CP-CML, AP-CML, and BP-CML (all P < .001), but not for the de novo Ph+ ALL patients (P = .052).

In patients with CP-CML treated with ponatinib, the adjusted median overall survival was significantly longer compared with those in the allogeneic SCT cohort; the median was not reached (45.9–NR) vs 103.3 months (6.6–103.3; P = .013). The hazard ratio (HR) was 0.37 (95% CI: 0.16–0.84; P = .017).

In patients with AP-CML, median overall survival was not significantly different between the 2 treatment groups; for ponatinib, the median was not reached vs 55.6 (11.4–NR) months; P = .889; HR 0.90 [95% CI: 0.20, 4.10; P = .889]).

Among patients with BP-CML, ponatinib was associated with significantly shorter overall survival compared with allogeneic SCT. Median overall survival was 7.0 (3.5–11.0 vs 10.5 (5.8–49.0) months (P = .026); HR 2.29 (95% CI: 1.08, 4.82, P = .030).

Ph+ ALL patients treated with ponatinib had nominally shorter median overall survival than allogeneic SCT, 6.7 (4.0–15.3 vs 32.4 (7.8–NR) months; P = .119; HR 2.77 (95% CI: 0.73–10.56, P = .136).

Study limitations include the small sample size in each disease phase.

Physicians should base decisions on the benefits and risks of each treatment option and availability of allogeneic donor,” Dr. Nicolini concluded.


1. 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. Oral presentation at: 57th American Society of Hematology (ASH) Annual Meeting; December 7, 2015, Orlando, FL.