ASH Annual Meeting and Exposition

ASH Annual Meeting and Exposition

Perspective from Nicholas Short, MD
December 09, 2017
4 min read

Ponatinib appears safe, effective for older patients with Philadelphia chromosome-positive ALL

Perspective from Nicholas Short, MD
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ATLANTA — The combination of ponatinib with steroids induced complete hematological response among more than 90% of elderly or unfit patients with Philadelphia chromosome-positive acute lymphoblastic leukemia, according to the results of a phase 2 prospective study presented at the ASH Annual Meeting and Exposition.

“We are starting to believe that for Ph+ patients aged 60 years or older, ponatinib [Iclusig, Takeda Oncology] with steroids is safe and effective and could be a mainstay treatment in these patients,” Giovanni Martinelli, associate professor of hematology at University of Bologna, said during his presentation. “We thought before the study that ponatinib would show an advantage, but not in this way. We didn’t expect it to be so successful.”

Tyrosine kinase inhibitors have significantly improved survival among patients with Ph+ALL. Studies reported that adults with Ph+ALL who received ponatinib in combination with chemotherapy achieved a 3-year EFS rate of 69% and a 3-year OS of 83%. However, TKIs combined with chemotherapy are associated with higher toxicities among elderly or unfit patients.

In the GIMEMA LAL1811 trial, researchers examined the efficacy and safety of ponatinib plus steroids among 42 patients either deemed unfit or aged 60 years or older (median age, 69 years; range, 27 to 85) with untreated Ph+ALL. Unfit patients (n = 9) could not receive intensive chemotherapy and stem cell transplantation.

Researchers assessed patients from March 2014 through December 2016.

Patients received 45 mg oral ponatinib daily for eight consecutive courses of 6 weeks. They also received steroids from 14 days prior to therapy until day 29 during the initial course. Patients received intrathecal therapy (methotrexate, cytarabine and dexamethasone) every 28 days for central nervous system disease prophylaxis.

Researchers obtained patient samples at each of the eight courses. They defined complete molecular response as BCR-ABL/ABL ratio below 0.01 or undetectable, and with a sensitivity of at least 30,000 molecules of ABL.

Complete hematological response served as the primary endpoint.

Median follow-up of the enrolled patients was 11.4 months.

At 6 weeks (1 course), 40 patients (95%) achieved complete hematologic response.

At 12 and 24 weeks (8 courses), 38 patients (90.5%) were in complete hematologic remission. Complete response dropped to 64% (n = 27) at 36 weeks and 42% (n = 18) at 48 weeks.

Two patients stopped treatment after 6 weeks due to disease relapse or excessive toxicity. Two patients dropped out after 12 weeks for medical decisions.


Researchers detected complete molecular response among 11 of 24 patients at 24 weeks (45.8%; 14 patients not evaluable).

Overall, 97.6% (95% CI, 93.1-100) achieved 6-month OS and 87.5% (95% CI, 76.5-99.9) achieved 1-year OS.

During the study, 36 of the 75 reported adverse events appeared related to ponatinib. Twenty-six events were considered serious, 13 of which were considered related to ponatinib. Researchers suspected one death to be related to ponatinib.

“There were no early complications, a high rate of minimal residual disease negativity, a very fast transcript reduction, long-term deep molecular remission and a great advantage in quality of life,” Martinelli said. “That makes single-agent ponatinib a good candidate for trials in a younger population.” – by Chuck Gormley


Martinelli G, et al. Abstract 99. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta.

 Disclosures: Martinelli reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.