Stop Combo Pulse Therapy in Low-Risk ALL After 1 Year: Trial

NEW YORK (Reuters Health) – Pulse therapy with vincristine and dexamethasone, which is typically continued throughout maintenance treatment for childhood acute lymphoblastic leukemia (ALL), can be safely omitted in children with low-risk disease after the first year, according to new trial data.

Omitting vincristine plus dexamethasone pulses after one year of treatment “should now become a standard of care for all low-risk patients,” Dr. Ching-Hon Pui of St. Jude Children’s Research Hospital, in Memphis, Tennessee, told Reuters Health by email.

Stopping the treatment “should decrease the acute adverse events and late sequelae of pulse therapy in patients, as well as the burden on their families,” Dr. Pui and colleagues write in The Lancet Oncology.

However, additional studies are needed to see if pulse therapy can be safely omitted in the population of children with intermediate-to-high-risk ALL, they note.

Their open-label, phase-3 non-inferiority trial enrolled 5,054 children with low-risk, intermediate-risk or high-risk ALL in continuous remission approximately one year after treatment.

Patients in each risk cohort were randomly assigned to receive (control group) or not receive (experimental group) seven pulses of intravenous vincristine plus oral dexamethasone during the second year of treatment. Median follow-up for patients who were alive at the time of analysis was 3.7 years.

In the low-risk cohort, there was no difference in the five-year event-free survival between the control group and the experimental group (90.3% vs. 90.2%; P=0.90).

“The one-sided 95% upper confidence bound for the difference in five-year event-free survival probability was 0.024, establishing non-inferiority,” the investigators report.

“We have performed analysis within each subtype of patients with low-risk ALL and found no differences in the event-free survival between randomized patients treated with or without pulses of vincristine plus dexamethasone after one year of treatment in all subtypes,” Dr. Pui told Reuters Health.

“The results should apply to clinical practice in the U.S. and around the world. We know that there are substantial racial and ethnic differences in the incidences of different subtypes or risk groups of ALL. However, as long as we use the same criteria to define low-risk ALL, the result should be the same,” Dr. Pui added.

There was also no between-group difference in five-year event-free survival in the intermediate-to-high-risk cohort (82.8% vs. 80.8%; P=0.90), “but the one-sided 95% upper confidence bound for the difference in five-year event-free survival probability was 0.055, giving a borderline inferior result for those in the experimental group,” the investigators say.

As expected, children with intermediate-to-high-risk ALL who received pulse therapy were more likely to develop grade-3 to -4 pneumonia and vincristine-related peripheral neuropathy. The incidence of grade-5 fatal infection was similar between the control group and the experimental group in both the low-risk cohort and intermediate-to-high risk cohort.

SOURCE: The Lancet Oncology, online July 27, 2021.

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