Low-Intensity Chemotherapy Without Intensified Pegaspargase Cured Most Patients With Low-Risk B-ALL

Data in the Journal of Clinical Oncology found that low-intensity chemotherapy without additional intensified pegaspargase cured almost all patients treated on the Children’s Oncology Group AALL0331 trial.

Research from the AALL0331 trial (NCT03914625) in patients with B-acute lymphoblastic leukemia (ALL) who were identified as having low-risk criteria by clinical, early response, and favorable cytogenetics found that standard 3-drug therapy without the addition of intensified pegaspargase cured nearly all patients, according to data published in the Journal of Clinical Oncology.

More, the standard therapy without pegaspargase in an outpatient setting is known to produce limited toxicities and a very low risk of significant treatment-related morbidity or mortality.

“Our primary objective was to determine if post-induction pegaspargase intensification improved the continuous complete remission rate from 92% to 96% and we found no difference between arms,” wrote the investigators.

Overall, the 6-year continuous complete remission (CCR) for the low-risk cohort was 94.7% plus or minus 0.6%. Focusing on the research 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 6-year overall survival (OS) rate 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% vs 99.2% plus or minus 0.3%, respectively; P = .99).

Total outcomes for both CCR (HR, 1.95; P = .0004) and OS (HR, 5.42; P < .0001) were found to be significantly superior for patients in the low-risk population compared with a subset of standard-risk patients who received the same therapy and had the same early responses but did not have favorable or unfavorable cytogenetics.

“Results of this secondary study objective showed that favorable genetics was associated with striking advantages in both CCR and OS,” wrote the investigators. “To our knowledge, we are the first to report this important finding based on a prospective comparative analysis.”

The trial enrolled 5377 total patients with National Cancer Institute standard-risk B-ALL between 2005 and 2010. After the 3-drug induction—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 childhood ALL treatment in low- and middle-income countries and provide a compelling argument to develop fluorescence in situ hybridization and MRD testing to identify these low-risk patients in those settings,” wrote the investigators. “Moreover, 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. Favorable Trisomies and ETV6-RUNX1 Predict Cure in Low-Risk B-Cell Acute Lymphoblastic Leukemia: Results From Children’s Oncology Group Trial AALL0331. J Clin Oncol.March 19, 2021. doi:10.1200/JCO.20.02370