In an analysis of long-term follow-up of the UKALL2003 trial reported in the Journal of Clinical Oncology, Anthony V. Moorman, PhD, and colleagues found that whereas initial risk of relapse in children and young adults with acute lymphoblastic leukemia differed according to risk factors, risk coalesced across groups approximately 5 to 6 years after diagnosis and decreased to < 1% (defined as cure) across groups at approximately 6 to 7 years.
Study Details
The objective of the UKALL2003 trial was to assess outcomes of adjustment of treatment intensity on the basis of measurable residual disease (MRD) stratification. A total of 3,113 patients were enrolled, including 521 MRD low-risk and 533 MRD high-risk patients who underwent treatment random assignment. The conditional probability of relapse through 12 years after diagnosis was estimated for patients who remained event-free at the start of each follow-up year. Time to cure was defined as the point at which the risk of relapse was < 1%. Event-free survival was defined as time to relapse, second tumor, or death.
Key Findings
Median follow-up was 10.98 years (interquartile range = 9.19–13.02 years).
In the MRD low-risk group, 10-year event-free survival was 91.7% (95% confidence interval [CI] = 87.4%–94.6%) with one course of delayed intensification vs 3.7% (95% CI = 89.9%–96.1) with two delayed intensifications (adjusted hazard ratio [HR] = 0.73, 95% CI = 0.38–0.40, P = .3).
In the MRD high-risk group, 10-year event-free survival was 82.1% (95% CI = 76.9%–86.2%) with standard therapy vs 87.1% (95% CI = 82.4%–90.6%) with augmented therapy (adjusted HR = 0.68, 95% CI = 0.44–1.06, P = .09).
Long-term outcomes of the UKALL2003 trial confirm that low-risk patients can safely de-escalate therapy, while intensified therapy benefits patients with high-risk cytogenetics. Regardless of prognosis, the time to cure is similar across risk groups. This will facilitate communication to patients and families who pose the question ‘When am I/is my child cured?’— Anthony V. Moorman, PhD, and colleagues
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Among patients with high-risk cytogenetics, 10-year risk of relapse was 22.1% (95% CI = 15.1%–31.6%) among those receiving augmented therapy vs 52.4% (95% CI = 28.9%–80.1%) among those receiving standard therapy (P = .016).
Although the initial risk of relapse differed by MRD status and cytogenetic risk, as well as by sex and age, risk of relapse for all subgroups coalesced at approximately 5 to 6 years after diagnosis, with risk of < 1% observed across all subgroups at approximately 6 to 7 years. As stated by the investigators, “This suggests that, although the overall likelihood of a cure varies significantly by these key risk factors, the time to that cure is less heterogeneous.” In addition, the relative survival of UKALL2003 patients (including those with favorable and unfavorable risk factors) vs age-matched controls in the UK population was 96.0% (95% CI = 95.5%–96.7%). The excess mortality among patients decreased over time, such that it approximated 0 at around 6 years after diagnosis; as stated by the investigators, “[This finding indicates] that patients are statistically cured (ie, had the same mortality rate as the general population) after this time point.”
The investigators concluded, “Long-term outcomes of the UKALL2003 trial confirm that low-risk patients can safely de-escalate therapy, while intensified therapy benefits patients with high-risk cytogenetics. Regardless of prognosis, the time to cure is similar across risk groups. This will facilitate communication to patients and families who pose the question “When am I/is my child cured?”
Ajay Vora, FRCPath, of the Department of Haematology, Great Ormond Street Hospital, London, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Blood Cancer UK and Medical Research Council. For full disclosures of the study authors, visit ascopubs.org.
