Pulse Therapy Can Be Omitted for in Pediatric Low-Risk Acute Lymphoblastic Leukemia After 1 Year of Treatment

Vincristine plus dexamethasone pulse therapy can be omitted in pediatric patients who have low-risk acute lymphoblastic leukemia (ALL) beyond 1 year of treatment, according to findings from a study published in Lancet Oncology.

Data from the trial indicated that in the low-risk group, there was no difference in 5-year event free survival (EFS) between the control (90.3%; 95% CI, 88.4%-92.2%) and experimental group (90.2%; 95% CI, 88.2%-92.2%; P = .90). Additionally, the 5-year overall survival (OS) rates were 97.8% (95% CI, 96.9%-98.8%) and 97.3% (95% CI, 96.1%-98.5%; P = .70) in both respective groups. Investigators did not identify any differences in 5-year cumulative risk of isolated central nervous system relapse, overall relapse, and death during remission between the 2 groups.

“The omission of 7 pulses of vincristine plus dexamethasone therapy during the second year of maintenance therapy did not adversely affect [the] treatment outcome of childhood low-risk [ALL], as measured by [EFS, OS], and the cumulative risk of any relapse, in the largest cohort of patients studied to date,” the study’s investigators wrote.

The study initially included 6141 patients with newly diagnosed ALL with ALL. One year from diagnosis, 2923 patients with low-risk ALL and 2131 patients with intermediate-to-high-risk ALL were assigned randomly to either 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 intermediate-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. Additionally, 4 patients (15%) died of relapse and 4 (15%) died of transplant-related adverse effects. CAR T-cell therapy was given to 2 patients of whom 1 was alive and in remission for 1.6 years and the other died of relapse.

The median follow-up time was 3.7 years with 17% of patients (n = 833) having follow-ups for 5 or more years. Median follow-ups in the low-risk cohort were 3.9 years and 3.0 years in intermediate-to-high-risk cohorts. In the low risk group, 2 patients in both the control and experimental groups were taken off protocol by treating physicians as well as 6 patients in the control and one in the experimental group in the intermediate-to-high risk population.

Additional findings from the study 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 did not identify any differences between the control and 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 = .40).

When the analysis was limited to patients with intermediate-risk ALL, there was no significant difference 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 = .90) in both groups, respectively. Additionally, 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 = .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 and experimental groups. 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 the experimental groups. Those with intermediate-risk ALL, there was no significant difference between the control and experimental groups for 50-year EFS (P = .50) or 5-year OS (P = .99).

Investigators found that patients in the intermediate-to-high-risk group developed grade 3/4 pneumonia and vincristine-related peripheral neuropathy with the control group having a numerically higher incidence vs the experimental groups. Patients in the intermediate-risk group also had the same adverse effects.

Investigator caution that additional studies need to be done to determine if patients with intermediate-to-high-risk ALL can be omitted for therapy after 1-year, as well.

“Future studies of long-term survivors of childhood acute lymphoblastic leukemia are needed to determine whether the omission of the seven pulses of vincristine plus dexamethasone would substantially decrease the long-term sequelae associated with vincristine and glucocorticoid treatment, such as peripheral neuropathy, metabolic syndrome, muscle weakness, growth retardation, and decreased energy balance,” the study’s authors concluded.

Reference

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. Published Online July 27, 2021;S1470-2045(21)00328-4. doi:10.1016/S1470-2045(21)00328-4