In general, adolescent and young adult (AYA) patients, aged 16–30 years old, with high-risk acute lymphoblastic leukaemia (HR-ALL) have inferior outcomes compared to younger HR-ALL patients. The phase III AALL0232 trial enrolled the largest number of AYA B-ALL patients to date, demonstrating significantly inferior survival and greater rates of treatment-related toxicities compared to younger patients.
KEY MESSAGE FOR CLINICAL PRACTICE
Although treatment intensification strategies have improved outcomes in younger patients, these have not translated into better survival in those older.
AALL0232 was a phase III randomised Children’s Oncology Group trial for newly diagnosed HR B-ALL (1–30 years). Between 2004 and 2011, 3,154 patients enrolled with 3,040 eligible and evaluable for induction. AYA patients comprised 20% of patients (16–21 years, N= 551; 22–30 years, N= 46). Five-year event-free survival and overall survival was 65.4 ± 2.2% and 77.4 ± 2.0% for AYA patients compared to 78.1 ± 0.9% and 87.3 ± 0.7% for younger patients (p< 0.0001). Five-year cumulative incidence of relapse was 18.5 ± 1.7% for AYA patients and 13.5 ± 0.7% for younger patients (p= 0.006), largely due to increased marrow relapses (14.0 ± 1.5% versus 9.1 ± 0.6%; p< 0.0001). Additionally, induction failure rate was higher in AYA (7.2 ± 1.1% versus 3.5 ± 0.4%; p< 0.001) and post-induction remission deaths were significantly higher in AYA (5.7 ± 1.0% versus 2.4 ± 0.3%; p< 0.0001). Although treatment intensification has improved outcomes in younger patients, they have not been associated with the same degree of improvement for older patients.
COG AALL0232 enrolled the largest number of AYA patients to date on a paediatric B-ALL study and demonstrated significantly inferior EFS and OS and greater rates of treatment-related toxicity for AYA compared to younger patients. Although AYA patients had inferior early response, a higher frequency of Ph-like ALL, and a much lower frequency of ETV6-RUNX1-positive ALL, older age retained prognostic significance in multivariable analyses. Importantly, the results show no improvement in AYA outcomes compared to studies reported more than 15 years ago. Although treatment intensification strategies have improved outcomes in younger patients, these have not translated into better survival in those older. Thus, future trials must identify novel strategies to both improve outcomes and further reduce toxicity in the AYA cohort. Current clinical trial strategies that are being tested by COG include incorporating tyrosine kinase inhibitors for recently described Ph-like ALL subsets, as well as novel therapies such as blinatumomab, inotuzomab ozagamicin, and/or chimeric antigen receptor T-cell therapies.
Reference
Top
