Ponatinib Regimen Shows Long-term Efficacy in Acute Lymphoblastic Leukemia


Key Takeaways

  • Ponatinib, chemotherapy, and alloHSCT regimen achieved a 4-year overall survival probability of 92% in Ph+ ALL patients.
  • Complete molecular response rates were 47% post-induction and 71% post-consolidation, with no relapses before alloHSCT.
Josep-Maria Ribera MD, PhD

Josep-Maria Ribera MD, PhD

A regimen of ponatinib (Iclusig), chemotherapy, and allogeneic hematopoietic stem cell transplantation (alloHSCT) can lead to long-term survival in adult patients with newly diagnosed Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL), according to 4-year data from the phase 2 PONALFIL trial shared during the 2024 EHA Congress.1

The trial included 30 patients with Ph+ ALL who were treated with an induction regimen of ponatinib at 30 mg/day plus vincristine, daunorubicin, and prednisone. Consolidation was then composed of ponatinib at the same dosage plus high-dose methotrexate, cytarabine, mercaptopurine and etoposide. All patients in complete response were scheduled to then receive alloHSCT.

Central nervous system (CNS) prophylaxis comprised methotrexate, cytarabine, and hydrocortisone, with patients receiving 5 doses of this regimen before transplant and then 5 doses during and after transplant. Pre-emptive use of maintenance ponatinib following transplant was allowed if there was “MRD persistence or reappearance after alloHSCT,” the authors wrote on their EHA poster.

The complete molecular response (CMR) rate following induction was 47% (14 of 30 patients), and, following consolidation, the CMR rate was 71% (20 of 28 patients). The rates were similar, regardless of specific BCR::ABL1 isoforms.

There were no observed relapses prior to alloHSCT which was administered to 26 patients at a median time of 5.7 months (range, 4.2-9.6) between the start of treatment and transplant. Following transplant, all patients experienced CMR.

At a median follow-up of 4 years, 28 patients were alive for a 4-year overall survival (OS) probability of 92% (95% CI, 72%-98%). With molecular relapse as the measured event, the 4-year event-free survival (EFS) probability was 66% (95% CI, 45%-81%). OS and EFS did vary by the type of BCR::ABL1 isoform.

There were 2 patient deaths related to receiving alloHSCT. One patient died at 3 months due to graft-versus-host disease and 1 patient died at 24 months due to cytomegalovirus. There was 1 patient who withdrew from the study because of severe transplant-related liver toxicity. Another patient had isolated pleural relapse at over 2 years (25 months) following alloHSCT. The investigators re-administered the same induction regimen, and the patient received a second alloHSCT. At the time of the study analysis, the patient was alive and in CMR at 3 months post-transplant.

There were 5 patients with molecular relapse at a median time of 9 months (range, 4-20) post-alloHSCT who were successfully treated with maintenance ponatinib. Bone marrow relapse occurred in 2 of these patients and both were successfully treated, 1 with CD19 CAR T-cell therapy plus ponatinib and 1 with ponatinib plus the FLAG-Ida regimen of fludarabine, cytarabine, granulocyte-colony stimulating factor, and idarubicin. No patients experienced CNS relapse.

Baseline characteristics showed that the median patient age was 49 years (range, 19-59), 57% (n = 17) of patients were male, and 43% (n = 13) of patients were female. The median white blood cell count was 6.4 x 109/L (range, 0.6-359.3), median hemoglobin was 90 g/L (range, 63-145), median platelets was 38.5 x 109/L (11-206), and median LDH was 358.5 (range, 160-3278). Among the 21 patients for whom ECOG performance status was available, 86% (n = 18) had an ECOG performance status less than 2.

Phenotype was available for 29 of the 30 patients. The vast majority (90%) were common B, 3% were pre-B, and 7% were pro-B. BCR::ABL1 isoforms included p190 (67%), p210 (30%), and p230 (3%).

Ponatinib has 2 FDA-approved indications for the treatment of patients with Ph+ ALL.2 The first is for use in combination with chemotherapy for newly diagnosed patients, and the second is for single-agent use in patients with Ph+ ALL and no kinase inhibitor alternatives or patients with T315I-positive Ph+ ALL.


  1. Ribera JM, Morgades M, Ribera J, et al. Ponatinib, chemotherapy and transplantation for newly diagnosed adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (PH+ ALL). Final results of the phase 2 PONALFIL trial. Presented at the European Hematology Association (EHA) 2024 Hybrid Congress; Madrid, Spain; June 13-16, 2024. P398.
  2. Iclusig prescribing information. FDA. Accessed June 14, 2024.

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