CHICAGO – Putting adolescent and young adult leukemia patients on pediatric regimens improved their event-free survival rate at 5-years, but they still did not fare as well as younger patients in a clinical study.
The Children’s Oncology Group protocol randomized 2,571 patients up to 30 years of age in a comparison of treatment regimens for high-risk B-precursor acute lymphoblastic leukemia (ALL). Within this population, 501 patients were 16 years or older – an age group that historically has had poorer outcomes than younger patients.
The 5-year event-free survival rate reached 68% among adolescent and young adult (AYA) patients in the randomized phase III trial – better than the 50%-60% consistently reported in previous trials, according to Dr. Eric Larsen, lead author of the study. It fell short of the 80% achieved in younger patients, however (P less than .0001).
The AYA cohort also had lower rates of overall survival (79.8% vs. 88.4%; P less than .0001) and remission (97.2% vs. 98.8%; P = .0134), which investigators defined as less than 5% marrow blasts after induction therapy. They blamed the disparity in large part on a higher rate of marrow relapse in the older patients (15.2% vs. 9.0%; P less than .0007). CNS relapse occurred at a slightly higher rate in the AYA group – 5.2% vs. 3.7%, they noted, but the difference was not significant (P = .5776).
In another comparison, the AYA patients were more likely to relapse – the 5-year cumulative incidence was 21.3% vs. 13.4% for younger patients (P = .0018). Though induction mortality rates were not significantly different between AYA and younger patients, (2.4% vs. 1.8%; P = .36), postinduction remission deaths were significantly higher at 5 years (5.5% vs. 2.1%; P less than .0001).
After 5 years, survival curves tend to flatten for both age groups but remissions are still possible, Dr. Larsen said, underscoring the importance of the benchmark during a press briefing at the annual meeting of the American Society of Clinical Oncology.
"In clinical practice and in the research world we would never declare someone truly cured, but when you are out 5 years, the number of people who are going to relapse is extraordinarily small," he said.
Dr. Larsen, medical director of the Maine Children’s Cancer Program, Scarborough, and study chair of the Children’s Oncology Group protocol AALL0232, presented the analysis June 2 at the society’s annual meeting. He reported outcomes of the trial – it found that giving patients 50 times the standard methotrexate dose reduces recurrences – last year at ASCO.
The study was the first pediatric ALL trial to include patients up to 30 years, he noted. Typically, pediatric studies enroll patients up to 18 years of age, but investigators hoped to improve the outcomes of the AYA age group by delivering more aggressive regimens than are typically used in adult patients.
"This is an underserved area," commented Dr. Carol Aghajanian, moderator of the news briefing and chief of the gynecologic medical oncology service at Memorial Sloan-Kettering Cancer Center in New York.
"I do see young adults ... who have pediatric tumors," she said in an interview. "Do I treat them as a typical adult or as a child who is much younger? We have this group that gets lost in the middle because of their unique situation.
"We need to identify these patients and do studies that define the biology of their disease [and] what the right treatments are," she added.
What the current analysis has shown is that "future strategies to improve outcome in AYA patients with ALL should focus on both better leukemia control and reduced treatment toxicity," Dr. Larsen said in a summary of the findings. AYA patients "have more resistant leukemia and they are more susceptible to side effects," he added in an interview.
Many factors are thought to contribute to the poorer outcomes in AYA patients, according to Dr. Larsen. These include differences in disease biology leading to more aggressive cancers and less tolerance of chemotherapy side effects than is seen in pediatric patients. In addition, socioeconomic factors may be involved, as AYA patients are often in college or looking for jobs.
Compliance is an issue as well, he noted. Although parents take charge of administering oral medications for their children, teenagers want to be responsible for themselves – sometimes with less than optimal results.
"It’s pretty clear that adolescent patients have lower rates of compliance," Dr. Larsen said, adding that "lower compliances correlates with lower survival rates."
The authors said that they had no disclosures.