For children with B-cell acute lymphoblastic leukemia (B-ALL), postinduction central nervous system (CNS) prophylaxis with intrathecal triple therapy (ITT) did not improve 5-year disease-free survival, according to a study published in the Journal of Clinical Oncology. The study authors also noted that intrathecal methotrexate (IT MTX) is still the standard of care for children with B-ALL without overt CNS involvement.
The high-risk stratum of the Children’s Oncology Group AALL1131 (ClinicalTrials.gov Identifier: NCT01190930), a phase 3 clinical trial, was developed to determine whether ITT administered on a modified augmented Berlin-Franfurt-Münster chemotherapy backbone would improve disease-free survival and reduce CNS relapse without increasing neurotoxicity or compromising cognitive function in patients with high-risk B-ALL.
A total of 1734 eligible, evaluable patients with high-risk ALL were randomly assigned to either ITT treatment (866 patients; 54.6% male) or IT MTX treatment (868 patients; 51.5% male). The majority of patients in both the ITT and IT MTX groups were younger than age 10 years (76.0% and 76.7%, respectively).
Among patients in the ITT and IT MTX groups, 5-year disease-free survival was 90.6% vs 93.2%, respectively (P =.85). The overall survival was 96.7% vs 96.3%, respectively (P =.77). The hazard ratio for disease-free survival was .803 for IT MTX compared with ITT. IT MTX and ITT 5-year cumulative incidence rates of relapse were 5.6% vs 7.0%, respectively.
In addition, rates for cumulative incidence of bone marrow relapse, isolated CNS relapse, or a combination of both were not significantly different between the 2 groups. The toxicity rates among patients in the IT MTX and ITT groups did not significantly vary, and no significant differences in neurocognitive outcome were observed among patients in the 2 treatment groups.
“Current results showed no significant differences in reaction time after controlling for functioning early in treatment, and no differences in parent-rated problems with behavioral regulation or metacognition skills, which include ratings of task efficiency,” the investigators noted. “Longer follow-up will be needed to assess cognitive differences over time.”
Salzer WL, Burke MJ, Devidas M, et al. Impact of intrathecal triple therapy versus intrathecal methotrexate on disease-free survival for high-risk B-lymphoblastic leukemima: Children’s Oncology Group study AALL1131 [published online June 4, 2020]. J Clin Oncol. doi: 10.1200/jco.19.02892