© Todd Buchanan 2017
Attendees at ASH 2017 Photo courtesy of ASH
ATLANTA—Results of a phase 2 trial suggest treatment with ponatinib and steroids is feasible for patients with acute lymphoblastic leukemia (ALL) who are elderly and/or unfit for intensive chemotherapy and stem cell transplant.
More than 90% of patients who received this combination had a complete hematologic response at 24 weeks, and the treatment was considered well-tolerated.
“Ponatinib plus steroids is safe and effective in this fragile patient population, which is in urgent need of better therapeutic regimens,” said Giovanni Martinelli, MD, of the University of Bologna in Italy.
Dr Martinelli presented these findings at the 2017 ASH Annual Meeting (abstract 99*).
The trial (GIMEMA LAL 1811) was designed to evaluate whether steroids and ponatinib would be safe and effective in patients with newly diagnosed, Philadelphia chromosome-positive ALL who were older than 60 or ineligible for intensive chemotherapy and stem cell transplant.
The study included 42 such patients. Their median age was 68 (range, 27-85). Nine patients were younger than 60 and unfit.
Sixty-two percent of patients had the p190 fusion transcript, 10% had p210, and 29% had p190/210 transcripts.
Patients received oral ponatinib (45 mg/day) for 8 consecutive 6-week courses. They also received steroids from day -14 to day 29 of course 1.
Patients received intrathecal methotrexate, cytarabine, and dexamethasone every 28 days for central nervous system (CNS) disease prophylaxis. If they were positive for CNS disease at diagnosis, patients received intrathecal therapy twice a week until complete remission.
The median follow-up was 17.2 months.
Results
Thirty-nine patients received steroid pretreatment, and 14 of them had a reduction in circulating blasts of 75% or more before starting ponatinib.
The study’s primary endpoint was complete hematologic response, which occurred in 95.2% of patients at 6 weeks and 90.5% at 24 weeks.
Based on test sensitivity of at least 10,000 ABL molecules, 60.6% of evaluable patients (20/33) had a complete molecular response at 24 weeks.
One patient with relapse had evidence of T315L mutations, which correlates with ponatinib resistance. No other mutations were detected in patients with relapse.
The overall survival rate was 97.6% at 6 months and 87.5% at 1 year.
“The fast and deep reduction of the disease burden in the majority of patients, the ability of ponatinib to prevent the emergence of clones harboring BCR-ABL mutations, and the synthetic lethality with steroids on the BCR-ABL, FLT3, HCK, CDK6, MCL1 pathway most likely explain the therapeutic effectiveness of this regimen,” Dr Martinelli said.
He also said steroids and ponatinib were well-tolerated, with 15 patients continuing treatment at 24 weeks.
Of 75 adverse events (AEs), 36 were related to ponatinib. There were 26 serious AEs, and 13 of them were related to ponatinib.
Serious cardiovascular AEs included arterial disorders (n=3), embolism (n=2), acute coronary syndrome (n=2), acute myocardial infarction (n=1), cardiac failure (n=1), pericardial effusion (n=1), and ischemia (n=1).
Ten deaths were reported. The causes were identified as progression (n=4), cardiovascular disease (n=3), toxicity (n=1), toxicity and progression (n=1), and unknown cause (n=1).
Dr Martinelli reported no disclosures.
*Data in the presentation differ from the abstract.