The pace of progress in cancer research keeps getting faster and faster. However, the results of this research can take time to reach the medical community. The ASCO Plenary Series is a program developed by the American Society of Clinical Oncology (ASCO) to help speed the delivery of high-impact cancer research. In this series, cancer care providers gather online to learn about new, carefully selected research and discuss the study results with their colleagues.  

The February 2023 session in the ASCO Plenary Series features this study:   

  • Ponatinib is effective at treating people with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL)

Follow the discussion about research from the ASCO Plenary Series by using the #ASCOPlenarySeries hashtag on Twitter.  

Ponatinib is effective at treating people with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL)

Who does this study affect: People with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).

What did this study find: The phase 3 PhALLCON clinical trial found that the drug ponatinib (Iclusig) was more effective than imatinib (Gleevec) for people with Ph+ ALL when given in combination with a reduced dose of chemotherapy.

About 20% to 30% of adults with ALL have a type that has the “Philadelphia chromosome,” which forms when genetic material from a person’s chromosome 9 breaks off and attaches to chromosome 22. When this happens, a gene from chromosome 9 called ABL joins with a gene from chromosome 22 called BCR to make the BCR-ABL gene. This gene then makes the BCR-ABL protein, which can help leukemia cells grow.

Ponatinib and imatinib are both a type of targeted therapy called tyrosine kinase inhibitors (TKI) that work by blocking the BCR-ABL protein to stop the cancer from growing. For people with newly diagnosed Ph+ ALL, the current standard of care is treatment with a TKI in combination with chemotherapy or steroids. However, the leukemia often develops a resistance to this treatment and the cancer eventually starts to grow again. The researchers in this study wanted to compare ponatinib with imatinib to learn which drug could lead to better results in people with Ph+ ALL.

This study included 245 participants with newly diagnosed Ph+ ALL. They were randomly assigned to receive either ponatinib (164 participants) or imatinib (81 participants), in combination with chemotherapy for all participants. After 20 cycles of the combination treatment, participants then received ponatinib or imatinib alone until their disease progressed or their side effects worsened. The median age of the participants in the study was 54 years. The median is the midpoint, meaning half of the participants were older than 54 and half were younger.

During the study, the participants were monitored for a median of 20 months for ponatinib and 18 months for imatinib. After the first 3 cycles of treatment, called the induction phase, the study found that the response rate was higher in the ponatinib group than in the imatinib group. Among those in the ponatinib group, 34% had a minimal residual disease (MRD) negative complete response, meaning there were no signs of disease. For those in the imatinib group, 17% had an MRD-negative complete response. The participants receiving ponatinib also had lower rates of death, the treatment not working, and disease recurrence when compared with those who received imatinib. Both groups experienced similar rates of side effects.

When the researchers began studying the data, 78 patients were still receiving treatment, including 42% of those in the ponatinib group and 12% of those in the imatinib group. If patients stopped the study treatment, it was because they received a stem cell transplant (31% of those in the ponatinib group and 37% in the imatinib group), due to side effects (12% in both groups), or because the treatment was not working (7% of those in the ponatinib group and 26% in the imatinib group).

What does this mean for patients: For people with newly diagnosed Ph+ ALL, ponatinib may be an effective treatment option when used in combination with chemotherapy.

Read this abstract and authors’ disclosures on

The potential benefit to patients who achieve this early deep response may be important to improve long-term survival outcomes. The trial results indicate ponatinib as a potential standard of care for patients newly diagnosed with Ph+ ALL.”  

—  lead study author Elias Jabbour, MD
The University of Texas MD Anderson Cancer Center
Houston, Texas