Ponatinib significantly improves minimal residual disease (MRD)-negativity complete response (CR) rates in patients with newly diagnosed Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL), when compared with imatinib, according to research presented at a February 2023 ASCO Plenary Session.

“Ponatinib compared with imatinib in combination with low-dose chemotherapy in newly diagnosed Ph+ ALL demonstrated a significantly higher rate and clinically meaningful MRD-negativity CR rate at the end of induction,” said Elias Jabbour, MD, of the University of Texas MD Anderson Cancer Center in Houston, in a presentation of the findings.

Ponatinib Bests Imatinib in the 1L Setting

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These findings come from the phase 3 PhALLCON trial (ClinicalTrials.gov Identifier: NCT03589326), which enrolled 245 patients with Ph+ ALL. They were randomly assigned 2:1 to receive ponatinib (n=164) or imatinib (n=81) with reduced-intensity chemotherapy through the end of induction, consolidation, and postconsolidation. After cycle 20, patients were administered ponatinib or imatinib monotherapy until disease progression or unacceptable toxicity.

In the overall cohort, the median age of those enrolled was 54 years in the ponatinib arm (range, 19-82) and 52 years in the imatinib arm (range, 19-75).

At the data cutoff (August 2022), 78 patients were given the study treatment, including 42% ponatinib and 12% imatinib. The main reasons for discontinuation were hematopoietic stem cell transplantation (31% vs 37%, respectively), adverse events (AEs; 12% for both groups), and lack of efficacy (7% vs 26%, respectively).

After median follow-up times of 20 months and 18 months in the ponatinib and imatinib arms, respectively, there was a significantly higher MRD-negativity CR rate seen with ponatinib compared with imatinib (34.4% vs 16.7%; P =.0021).

Although the data were immature, ponatinib showed a trend toward improved event-free survival (EFS) (hazard ratio [HR], 0.65; 95% CI, 0.39-1.10). The median PFS was 20.0 months in the ponatinib arm and 7.9 months in the imatinib arm (HR, 0.58; 95% CI, 0.41-0.83). The median overall survival (OS) was not reached in either arm (HR, 0.76; 95% CI, 0.38-1.52).

With respect to safety, treatment-emergent AEs (TEAEs) were similar between the treatment arms. Grade 3-4 TEAEs occurred in 90% and 93% and grade 5 TEAEs in 5% and 5% in the ponatinib and imatinib arms, respectively. The rates of arterial occlusive events were infrequent and comparable between the arms.

“Taken together, the efficacy and safety results demonstrate a favorable benefit/risk assessment for ponatinib and should be considered be a standard of care frontline therapy in patients with newly diagnosed Ph+ ALL,” Dr Jabbour concluded.

Putting the Results in Context

In a follow-up presentation, discussant Anjali S. Advani, MD, of the department of hematologic oncology and blood disorders at the Cleveland Clinic in Cleveland, OH, stated “Ponatinib was associated with deeper and more durable responses than imatinib and there was no increased risk of toxicities with ponatinib vs imatinib, including arterial occlusive events or venous thromboembolic events.”

“This is the only prospective randomized trial comparing tyrosine kinase inhibitors (TKIs) in this patient population,” Dr Advani added. “Overall, the results were encouraging with no treatment-related emergent AEs.”

“Importantly, however, this patient population had a low incidence of cardiovascular risk factors, and thus the question becomes whether these results are generalizable to the general ALL patient population,” she continued. “We still need to evaluate the risk/benefit of ponatinib in patients with cardiovascular comorbidities…In a younger patient with relatively few or no cardiovascular comorbidities, ponatinib represents an exciting treatment option.”

Role of Newer Agents

“The current treatment landscape is changing quickly, and so is the standard of care,” Dr Advani explained. “The question we struggle with now is whether we should be using antibody-based therapies in combo with TKIs — further studies are needed to answer this question.”

Disclosures: The PhALLCON trial was sponsored by Takeda Development Center Americas, Inc. Please see the original references for a full list of disclosures.


Jabbour E, Kantarjian HM, Aldoss I, et al. First report of PhALLCON: A phase 3 study comparing ponatinib (pon) vs imatinib (im) in newly diagnosed patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Presented at: 2023 February ASCO Plenary Series; February 15, 2023. Abstract 398868.