Chicago, IL—Moving nelarabine (Arranon), a T-cell–specific drug, up front combined with backbone chemotherapy (ie, COG-augmented Berlin-Frankfurt-Münster [aBFM]) improved survival by approximately 10% in the largest-ever randomized clinical trial enrolling newly diagnosed children and young adults with T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LL).
Overall survival (OS) was also excellent for all patients enrolled in this large, phase 3 federally funded clinical trial.
The OS for all patients was 90.2% at 4 years, and the 4-year event-free survival was 84.1%. In patients at moderate or high risk for T-ALL recurrence, the addition of nelarabine to aBFM chemotherapy led to 4-year disease-free survival in 88% of patients compared with 83% in patients who did not receive nelarabine.
Approximately 80% of children and young adults with T-ALL or T-LL are alive at 4 or 5 years after diagnosis with the use of standard chemotherapy. The rates reported in this study are the highest reported to date for these T-cell leukemias.
"These are outstanding overall outcomes. Nelarabine improves disease-free survival for children and young adults with T-ALL and should become a new standard of care for this population," said lead investigator of the study Kimberly P. Dunsmore, MD, Chair of Pediatrics, Carilion Clinic, Roanoke, VA.
The study results apply to nelarabine plus the specific chemotherapy regimen used in this trial and are not generalizable to other chemotherapy regimens. Nelarabine is FDA approved for relapsed T-ALL and T-LL. This is the first phase 3 randomized clinical trial to evaluate the drug in the first-line setting.
The study enrolled 1545 participants aged 1 to 30 years, with either T-ALL (94%) or T-LL (6%). All patients received aBFM chemotherapy and were randomized to receive high-dose methotrexate in the hospital or as an escalating-dose methotrexate in the outpatient setting. Intermediate- and high-risk patients with T-ALL or T-LL were randomized to receive nelarabine or no nelarabine, and all received cranial irradiation.
The best arm in the study was nelarabine plus escalating doses of methotrexate, with a 4-year disease-free survival rate of 91%.
Patients with T-LL (6% of participants) had no benefit from nelarabine, but the 4-year disease-free survival was still more than 85% for this group of patients.
Patients receiving escalating doses of methotrexate had 4-year disease-free survival of 89.8% versus 78% for those receiving high-dose methotrexate. Previous studies have had mixed results when comparing escalating doses versus high doses of methotrexate, but Dr Dunsmore advocates escalating doses based on a previous study she co-authored.
A small group of 43 patients with T-ALL who failed induction therapy were nonrandomly assigned to receive high-dose methotrexate plus nelarabine. The 4-year disease-free survival in this group was 54%, more than double the expected rate of 20% based on historical results.
Toxicity and neurotoxicity were not significantly different among the 4 arms of the trial. The rate of peripheral neurotoxicity was 8% in all 4 arms of the trial.
ASCO President Bruce E. Johnson, MD, FASCO, Chief Clinical Research Officer, Dana-Farber Cancer Institute, Boston, moderated a press cast where these data were presented.
Commenting on these results, Dr Johnson said, "We now know it is possible to significantly boost survival in children and young adults with rare forms of leukemia and lymphoma, without introducing additional harsh side effects that can impair their quality of life."
He added, "Previously, only 80% of patients with these T-cell malignancies survived for 4 or 5 years. This study shows up-front use of nelarabine improves survival."