Adolescent and young adult (AYA) patients (ages 16 to 30) with high risk acute lymphoblastic leukaemia (HR- ALL) had poorer outcomes than younger patients (ages 1 to 15), with lower rates of both event-free survival and overall survival, in a major phase III study of ALL treatment.

The findings point to the need for new strategies to improve leukaemia control and lower treatment toxicity for this older age group.

The randomised trial tested four treatment regimens for high-risk B-precursor ALL.

The treatment outcome data based on treatment regimen were presented at the 2011 ASCO Annual Meeting.

This year, the investigators report on event-free survival and overall survival of AYA patients compared to younger patients.

Although there is historical data that suggests that AYA patients with HR-ALL have inferior outcome, to date there has not been a trial with substantial numbers of patients who received the same treatment to make a direct comparison, said lead study author Eric Larsen, MD, medical director of the Maine Children’s Cancer Program and Study Chair of the Children’s Oncology Group protocol AALL0232.

“This study tells us that the inferior outcome for AYA patients is the result of more resistant disease, resulting in higher rates of relapse and higher toxicity from treatment,” Dr. Larsen said. “We have to find novel agents to better eradicate the leukemia, but while we want to intensify therapy, we also have to reduce toxicity.”

The study included 501 AYA patients, the largest cohort of this age group to date in a single cancer clinical trial. There were 466 patients age 16 to 21 and 35 patients aged 22 to 30. the AYA patients made up 20 percent of the overall trial enrollment of 2,574. Historically paediatric leukaemia studies cut off enrollment at age 18, but this trial was designed to include young adults up to age 30.

Five-year event-free survival—defined as having no evidence of disease—was 68 percent in the AYA patients compared to 80.9 percent in the young patients. Overall survival (OS) was 79.8 percent in the AYA patients compared to 88.4 percent in the younger patients. These differences were highly statistically significant.

AYA patients had a higher rate of relapse, 21.3 percent, compared to 13.4 percent for younger patients. This was also statistically significant. The relapses were primarily due to a higher rate of bone marrow relapse in the AYA patients, rather than central nervous system relapse.

The treatment strategy of the trial was to try to improve disease control in the central nervous system. There was no statistically significant difference in CNS relapse between AYA and younger patients.

Toxic deaths that occurred after induction therapy and remission were significantly higher in the AYA patients— 5.5 percent vs. 2.1 percent.

As a result of this study, the Children’s Oncology Group is considering several options to both enhance leukaemia control and also reduce the toxicity of treatment. It is hoped that future strategies will continue to improve the outcome for AYA patients with HR-ALL. 

Source: ASCO