Pulse Therapy Can Be Omitted for in Pediatric Low-Risk Acute Lymphoblastic Leukemia After 1 Year of Treatment
According to findings from a study published in Lancet Oncology, vincristine plus dexamethasone pulse therapy may be withheld in pediatric patients with low-risk acute lymphoblastic leukemia (ALL) after more than 1 year of treatment.
Data from the study indicated that in the low-risk group, there was no difference in 5-year event free survival (EFS) between the control group (90.3%; 95% CI, 88.4%-92.2% ) and the experimental group (90.2%; 95% CI, 88.2%-92.2%; P = 0.90). In addition, 5-year overall survival (OS) in both respective groups was 97.8% (95% CI, 96.9%-98.8%) and 97.3% (95% CI, 96.1% -98.5%, p = 0.70). Researchers identified no differences in 5-year cumulative risk of isolated central nervous system relapse, overall relapse, and death during remission between the 2 groups.
“Omitting 7 pulses of vincristine plus dexamethasone therapy during the second year of maintenance therapy did not adversely affect [the] treatment outcome of low risk in children [ALL], as measured by [EFS, OS], and the cumulative risk of relapse, in the largest cohort of patients studied to date,” the study researchers wrote.
The study initially included 6141 patients with newly diagnosed ALL with ALL. One year after diagnosis, 2923 patients with low-risk ALL and 2131 patients with intermediate to high-risk ALL were randomly assigned to the control or experimental cohorts. For low-risk patients, 1442 were randomized to the control group and 1481 were assigned to the experimental group. In the medium to high risk population, 1071 were assigned to the control cohort and 1060 were assigned to the experimental cohort.
Of the patients with high-risk ALL (n = 126), hematopoietic cell transplantation was performed in 26 patients, of whom 70% (n = 18) were alive and in remission for 0.4 to 4.6 years with a median time of 2.3 years. In addition, 4 patients (15%) died from relapse and 4 (15%) died from transplant-related adverse events. CAR T cell therapy was given to 2 patients of which 1 was alive and in remission for 1.6 years and the other died of relapse.
The median duration of follow-up was 3.7 years, with 17% of patients (n = 833) having a follow-up of 5 years or longer. The median follow-ups in the low-risk cohorts were 3.9 years and 3.0 years in the medium to high-risk cohorts. In the low-risk group, 2 patients in both the control and experimental groups were taken off the protocol by treating physicians, as well as 6 patients in the control group and one in the experimental group in the medium-to-high-risk population.
Additional study findings indicated that the 5-year EFS rate for all randomized patients was 79.9% (95% CI, 78.7%-81.2%) and the 5-year OS rate was 90, 3% (95% CI, 89.4%-91.2). %). Investigators identified no differences between the control group and the experimental group for patients with intermediate to high risk ALL in the 5-year EFS (82.8%; 95% CI, 80.0%-85.7% vs 80.8 %; 95% CI, 77.7%-84.0%;P=.90). Similar findings were identified for the 5-year OS (92.3%; 95% CI, 90.3%-94.4% vs 93.4%; 95% CI, 91.4%-95.4%; P = 0.40).
When the analysis was limited to patients with intermediate-risk ALL, no significant difference was found between the control and experimental groups, with investigators reporting a 5-year EFS rate of 82.7% (95% CI 79, 9%-85.7) and 80.7% (95% CI, 77.6-83.9; P = 0.90) in both groups, respectively. In addition, investigators reported a 5-year OS rate of 92.5% (95% CI, 90.6%-94.6%) and 93.3% (95% CI, 91.3%-95.3 %; P = 0.50) in each respective group.
In the post-hoc analysis for patients with low-risk ALL, there was no significant difference in 5-year EFS (P = .20) or 5-year OS (P = .40) between the control group and the experimental group. In intermediate to high risk patients, there was no significant difference for 5-year EFS (P = .50) or 5-year OS (P = .90) between the control and experimental groups. In those with intermediate-risk ALL, there was no significant difference between the control and experimental groups for 50-year EFS (P = 0.50) or 5-year OS (P = 0.99).
Researchers found that patients in the medium-to-high-risk group developed grade 3/4 pneumonia and vincristine-related peripheral neuropathy, with the control group having a numerically higher incidence than the experimental groups. Patients in the medium-risk group also had the same side effects.
The researchers caution that additional studies need to be done to determine whether patients with medium-to-high-risk ALL can also be left out of therapy after 1 year.
“Future studies of long-term survivors of childhood acute lymphoblastic leukemia are needed to determine whether omitting the seven pulses of vincristine plus dexamethasone would significantly reduce the long-term effects associated with vincristine and glucocorticoid treatment, such as peripheral neuropathy, metabolic syndrome, muscle weakness.” , stunted growth and impaired energy balance,” the study authors concluded.
Yang W, Cai J, Shen S, et al. Pulse therapy with vincristine and dexamethasone for childhood acute lymphoblastic leukemia (CCCG-ALL-2015): an open-label, multicenter, randomized, phase 3, non-inferiority trial. Lancet Oncol. Published online July 27, 2021;S1470-2045(21)00328-4. doi:10.1016/S1470-2045(21)00328-4