A study of the AALL0331 study (NCT03914625) in patients with B acute lymphoblastic leukemia (ALL) identified by clinical, early response and favorable cytogenetics as low-risk subjects cured nearly all patients, according to data published in the Journal of Clinical Oncology.
In addition, standard therapy without pegaspargase in an outpatient setting is known to cause limited toxicities and a very low risk of significant treatment-related morbidity or mortality.
“Our primary goal was to determine whether post-induction pegaspargase intensification improved the continuous full remission rate from 92% to 96% and we found no difference between the arms,” the researchers wrote.
In total, the 6-year continuous complete remission (CCR) for the low-risk cohort was 94.7% plus or minus 0.6%. Targeting the study arms, there was no statistically significant difference between the intensified pegaspargase arm (95.3% plus or minus 0.8%) and the standard arm (94.0% plus or minus 0.8%; P = .13 ).
The percent overall survival (OS) at 6 years for the entire low-risk cohort was 98.7% plus or minus 0.3%, with no difference found between the intensified pegaspargase and standard arms (98.1 % plus or minus 0.5% versus 99.2% plus or minus 0.3%, respectively; P = 0.99).
The overall outcomes for both CCR (HR, 1.95; P = .0004) and OS (HR, 5.42; P <.0001) were found to be significantly better for patients in the low-risk population compared to a subgroup of standard-risk patients receiving the same therapy and had the same early responses, but had no favorable or unfavorable cytogenetics.
“The results of this secondary study objective showed that beneficial genetics were associated with striking benefits in both CCR and OS,” the researchers wrote. “To our knowledge, we are the first to report this important finding based on a prospective comparative analysis.”
The study enrolled a total of 5,377 patients with standard risk B-ALL from the National Cancer Institute between 2005 and 2010. After the induction of three drugs – a regimen of dexamethasone, vinicristine and pegaspargase – the cohort of eligible patients was 1,857 . These patients were then randomly assigned to standard therapy with or without 4 additional doses of pegaspargase at 3 week intervals during both consolidation and interim maintenance.
“These results have substantial implications for the treatment of ALL in children in low- and middle-income countries and provide a compelling argument for developing fluorescence in situ hybridization and MRD assays to identify these low-risk patients in those environments,” the researchers wrote. “In addition, our findings support efforts to reduce the burden of therapy in SR-low patients without compromising outcome.”
Mattano LA, Devidas M, Maloney KW, et al. Beneficial Trisomies and ETV6-RUNX1 Predict Healing in Low-Risk B-Cell Acute Lymphoblastic Leukemia: Results of Children’s Oncology Group Trial AALL0331. J Clin Oncol. March 19, 2021.doi: 10.1200 / JCO.20.02370