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Pediatric patients with low-risk acute lymphoblastic leukemia may be able to omit treatment with vincristine and dexamethasone pulse therapy after the first year of treatment.
A combination of vincristine and dexamethasone pulses may be omitted beyond the first year of treatment for pediatric patients with low-risk acute lymphoblastic leukemia (ALL), according to the results of the phase 3 CCCG-ALL-2015 study that were published in Lancet Oncology.
Within this patient population, investigators reported no difference in 5-year event-free survival (EFS) between the control arm (90.3%; 95% CI, 88.4%-92.2%) and the experimental arm (90.2%; 95% CI, 88.2%-92.2%; P = .90). Moreover, no difference in 5-year EFS was observed among intermediate- to high-risk patients in either the control (82.8%; 95% CI, 80.0%-85.7%) or the experimental groups (80.8%; 95% CI, 77.7%-84.0%; P = .90). For all randomized patients, the 5-year EFS was 79.9% (95% CI, 78.7%-81.2%) and 5-year overall survival (OS) was 90.3% (95% CI, 89.4%-91.2%).
“The omission of seven pulses of vincristine plus dexamethasone therapy during the second year of maintenance therapy did not adversely affect treatment outcomes of childhood low-risk acute lymphoblastic [leukemia], as measured by EFS, OS, and the cumulative risk of any relapse, in the largest cohort of patients studied to date. There was also no significant heterogeneity of treatment effect on event-free survival among any subgroups of patients,” the authors wrote.
A total of 6141 pediatric patients were registered to the open label, multicenter, randomized non-inferiority trial from January 2015 to February 2020. One year following diagnosis and treatment, a total of 2923 patients with low-risk ALL and 2131 patients with intermediate- to high-risk ALL were randomized into either the low-risk cohort (control, n = 1442; experimental, n = 1481) or the intermediate- to high-risk cohort (control, n = 1071; experimental, n = 1060).
Every patient was treated with dexamethasone for 4 to 5 days up front and subsequent remission induction prednisone, vincristine, daunorubicin, and pegaspargase on day 5 to day 28. Cyclophosphamide, mercaptopurine, and cytarabine were administered from day 29 to day 35. Both the low-risk and intermediate- to high-risk cohorts received maintenance therapy 54 weeks after diagnosis, which included 7 cycles of vincristine plus dexamethasone pulses that were given every 8 weeks over the course of 56 weeks. Those with low-risk ALL were given weekly methotrexate and daily mercaptopurine with or without pulse therapy consisting of a 1.5 mg/m2 dose of vincristine plus oral dexamethasone or 6 mg/m2 every day for 7 days on week 8.
Eligible patients were between the ages of 0 to 18 years old with newly diagnosed ALL that had been in remission for 1 year following initial treatment. Those who had a secondary malignancy or primary immunodeficiency were not eligible for enrollment on the trial.
The study's primary end point was difference in 5-year EFS between the control and experimental cohorts. Key secondary end points included incidence of central nervous system (CNS) relapse; any CNS relapse, any relapse, or death during remission, and 5-year OS between the 2 groups.
The study had a median follow up of 3.9 years for the low-risk cohort and 3.0 years for the intermediate- to high-risk cohort. Additional findings from the study indicated that there was no difference between the control group and experimental group in relation to the 5-year cumulative risk of isolate CNS relapse, any CNS relapse, any relapse, and death during remission.
Within the low-risk cohort, investigators did not identify a difference in infection rate, symptomatic osteonecrosis, or other complications during the second year of maintenance. The incidence of grade 3/4 pneumonia and vincristine-related peripheral neuropathy was higher among those with intermediate- to high-risk disease in the control group. No differences in grade 5 fatal infection were observed.
Yang W, Cai J, Shen S, et al. Pulse therapy with vincristine and dexamethasone for childhood acute lymphoblastic leukaemia (CCCG-ALL-2015): an open-label, multicentre, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2021;22(9):1322-1332. doi:10.1016/S1470-2045(21)00328-4