In a Chinese phase III trial (CCCG-ALL-2015) reported in The Lancet Oncology, Yang et al found that 1 year of maintenance therapy with pulsed vincristine and dexamethasone was noninferior to 2 years in low-risk pediatric patients with acute lymphoblastic leukemia and was borderline inferior in those with intermediate- to high-risk disease.
Study Details
In the open-label, noninferiority, multicenter trial, 5,054 newly diagnosed patients in continuous remission after 1 year of maintenance therapy with pulsed vincristine/dexamethasone were randomly assigned between January 2015 and February 2020 to receive no further vincristine/dexamethasone maintenance (experimental group) or seven pulses of vincristine (1.5 mg/m²) and dexamethasone (6 mg/m²/d for 7 days) during the second year of treatment (control group). Among patients with low-risk disease, 2,923 were randomly assigned to the experimental group (n = 1,481) or the control group (n = 1,442); among those with intermediate- to high-risk disease, 2,131 were randomly assigned to the experimental group (n = 1,060) or the control group (n = 1,071). The primary endpoint was difference in 5-year event-free survival between the experimental group and the control group for both the low-risk and intermediate- to high-risk cohorts; the noninferiority margin was a one-sided 95% upper confidence bound of 0.05.
Key Findings
Among patients with low-risk disease, the one-sided 95% upper confidence bound for the difference in probability of 5-year event-free survival between the experimental vs control group was 0.024, and for 5-year overall survival, it was 0.018—both meeting the noninferiority criterion. No significant difference (P = .90) was observed in 5-year event-free survival between the experimental group (90.2%, 95% confidence interval [CI] = 88.2%–92.2%) vs the control group (90.3%, 95% CI = 88.4%–92.2%). No significant difference (P = .70) in 5-year overall survival was observed between the groups (97.3% [95% CI = 96.1%–98.5%] vs 97.8% [95% CI = 96.9%–98.8%]).
Among patients with intermediate- to high-risk disease, the one-sided 95% upper confidence bound for 5-year event-free survival was 0.055, which did not meet the noninferiority criterion and showed a borderline inferior outcome for the experimental group. No significant difference (P = .90) was observed in 5-year event-free survival (80.8% [95% CI = 77.7%–84.0%] vs 82.8% [95% CI = 80.0%–85.7%]). No significant difference (P =.40) was observed in 5-year overall survival (93.4% [95% CI = 91.4%–95.4%] vs 92.3% [95% CI = 90.3%–94.4%]).
In the low-risk cohort, no significant differences were observed between the groups in the rates of infection, symptomatic osteonecrosis, or other complications during the second year of maintenance. In the intermediate- to high-risk cohort, the experimental group had lower rates of grade 3 and 4 pneumonia (0.9% vs 2.4%) and vincristine-related peripheral neuropathy (0.6% vs 1.6%). Fatal infection occurred in 0.3% vs 0.1% of the low-risk cohort and in 0.5% vs 0.6% of the intermediate- to high-risk cohort.
The investigators concluded: “Vincristine plus dexamethasone pulses might be omitted beyond 1 year of treatment for children with low-risk acute lymphoblastic leukemia. Additional studies are needed for intermediate- to high-risk acute lymphoblastic leukemia.”
Ching-Hon Pui, MD, of the Departments of Oncology, Global Pediatric Medicine, and Pathology, St. Jude Children’s Research Hospital, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was supported by VIVA China Children’s Cancer Foundation, the National Natural Science Foundation of China, U.S. National Cancer Institute, and others. For full disclosures of the study authors, visit thelancet.com.
