Best-Ever Survival Achieved in Treating T-Cell Leukemia in Young People

Results from the largest study to date in children and young adults with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) revealed, for this patient group, the best survival data to date .

Results of the Children’s Oncology Group AALL0434 study will be presented at the upcoming ASCO 2018 Congressas abstract number 10500. This noteworthy study was announced at a pre-congress press briefing.

Before this study began, patients’ 5-year survival rate was 80%; with this study, it exceeded 90%.

In the study, nelarabine (brand name Arranon) was added to standard chemotherapy. Nelarabine received approval in 2005 from the FDA for relapsed or recurrent acute lymphoblastic leukemia and lymphoblastic lymphoma. In Turkey, it is a medicine supplied from abroad. In this study, however, nelarabine was used closer to initial treatment rather than after disease recurrence, which appears to have improved outcomes for these patients.

The Largest Clinical Trial in History

This research is the largest clinical trial ever conducted in children and young adults with T-ALL and T-cell lymphoblastic lymphoma (T-LL). The study enrolled 1895 patients aged 1 to 30, with T-ALL (94%) or T-LL (6%). Patients were randomly assigned to one of four treatment regimens:

• escalating doses of methotrexate alone,
• escalating-dose methotrexate plus 6 cycles of nelarabine (5 days of treatment, 650 mg/m2 per day),
• high-dose methotrexate alone,
• high-dose methotrexate plus 6 cycles of nelarabine.

Study Results

• Across all groups, the 4-year overall survival rate was 90.2%, and the disease-free survival rate was 84.3%.
• Patients who did not enter remission (disappearance of all signs of disease) with induction (initial) treatment had a 4-year survival rate of 54%—twice the historical survival rates. Even though patients with T-LL did not benefit from nelarabine, their 4-year survival rate was still found to be a fairly good 85%.
• The 4-year disease-free survival rate for patients with T-ALL who received nelarabine was 88.9%, compared with 83.3% for those who did not; this difference was also statistically significant.
• Among patients receiving escalating-dose methotrexate, the 4-year disease-free survival rate was better in the group with added nelarabine (92.2% versus 89.8%).
• In the high-dose methotrexate groups, the 4-year disease-free survival rate again favored nelarabine, at 86.2% versus 78%.
• For patients with T-ALL whose induction treatment failed and who received high-dose methotrexate plus nelarabine, the 4-year disease-free survival rate was 54.8%. Adding nelarabine to treatment in patients with high-risk T-LL did not demonstrate a survival advantage.

In conclusion, the results of this comprehensive study, powerful enough to change clinical practice, are also highly encouraging in showing how far cancer medicine has come. Lead author Dr. Kimberly Dunsmore stated that their next steps would be to study nelarabine with a treatment plan that does not include cranial (brain) irradiation, to reduce long-term neurological side effects.

FURTHER READING: How Does Nelarabine Work?

Nelarabine is a chemotherapy medicine. DNA synthesis (production) uses purine nucleosides, which it mimics, causing cell death by blocking DNA production. After administration, nelarabine is converted into a molecule called arabinosylguanine nucleotide triphosphate (ara-GTP). This molecule accumulates in leukemia cells and produces mitosisS-phase-specific cytotoxic (cell-killing) and apoptotic effects.

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