As reported in the Journal of Clinical Oncology by Hayashi et al, the Children’s Oncology Group AALL0434 study has shown “excellent” outcomes with Capizzi-based methotrexate/pegaspargase (C-MTX) treatment in patients with newly diagnosed pediatric T-cell lymphoblastic lymphoma (T-LL). The addition of nelarabine to treatment in high-risk patients did not improve outcomes.
In the trial, 299 patients aged 1 to 31 years received the augmented Berlin-Frankfurt-Muenster (ABFM) C-MTX regimen. A total of 121 patients had high-risk disease, defined as ≥ 1% minimal detectable disease in the bone marrow at diagnosis or receipt of prior steroid treatment. High-risk patients were randomly assigned to receive (n = 60) vs not receive (n = 61) six 5-day courses of nelarabine incorporated into ABFM C-MTX treatment.
Induction failure was defined as failure to achieve at least partial response by the end of 4-week induction treatment. Patients with induction failure had nelarabine added to treatment (n = 2). No patients received prophylactic cranial radiation. Patients with central nervous system (CNS) 3 disease (cerebrospinal fluid white blood cell count > 5/μL with blasts or cranial nerve palsies, brain/eye involvement, or hypothalamic syndrome) were not eligible for the trial.
Median follow-up was 4.9 years. At the end of induction, 98.8% of 282 evaluable patients had at least a partial response. Among all patients, 4-year event-free survival and overall survival were 84.7% and 89.0%. From end of induction, 4-year disease-free survival was 85.9%.
Disease-free survival at 4 years was 85.0% among standard-risk patients vs 87.4% among all high-risk patients (P = .2866). Event-free survival at 4 years was 82.4% among 176 patients with minimal detectable disease < 1% vs 89.5% among 97 patients with minimal detectable disease ≥ 1% (P = .3084).
Among high-risk patients, 4-year disease-free survival was 85.1% among those not receiving nelarabine vs 85.0% among those receiving nelarabine (P = .8338). The two patients who received nelarabine on the basis of induction failure were event-free during follow-up.
Additional analysis according to disease stage and tumor response did not indicate thresholds associated with differences in event-free survival. CNS relapse occurred in four patients (2%).
Nonrelapse deaths were observed in five patients, including three patients in the standard-risk group (due to fungal infection, unknown cause, and hemophagocytic lymphohistiocytosis, respectively) and two in the high-risk group (due to pancreatitis and cerebral edema, respectively). One patient developed a benign tumor, with no secondary malignancies being observed.
The investigators concluded, “COG AALL0434 produced excellent outcomes in one of the largest trials ever conducted for patients with newly diagnosed T-LL. The COG ABFM regimen with C-MTX provided excellent event-free survival and overall survival without cranial radiation.”
Robert J. Hayashi, MD, of the Division of Pediatric Hematology/Oncology, Washington University School of Medicine, St. Louis, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Institutes of Health and St. Baldrick’s Foundation. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.