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01-06-2018 | Oncology | News | Article

ASCO 2018

Adding nelarabine plus escalating methotrexate boosts pediatric, young adult T-ALL outcomes

medwireNews: The addition of nelarabine and an escalating dose of methotrexate to a standard chemotherapy regimen has achieved the best ever survival outcomes for children and young adults with a new diagnosis of T-cell acute lymphoblastic leukemia (T-ALL) who are at risk for recurrence, researchers say.

The COG AALL0434 investigators will report their phase III trial findings at the ASCO Annual Meeting 2018 in Chicago, Illinois, USA, citing 4-year overall survival (OS) and disease-free survival (DFS) rates with this regimen of 90.2% and 84.3%, respectively, for all T-ALL participants.

“Historically, about 80% of people live at least 4 years after being treated for their disease, but we felt we could and must do better,” presenting author Kimberly Dunsmore, from Virginia Tech Carilion School of Medicine in Roanoke, USA, commented in a press release.

“Our trial shows that we could further increase survival rates by about 10%, which is very encouraging.”

The 1895 participants were aged 1–30 years and the majority (94%) had T-ALL, while 6% had T-cell lymphoblastic lymphoma (T-LLy). All patients were given the Children’s Oncology Group augmented Berlin-Frankfurt-Munster (aBFM) chemotherapy regimen and were randomly assigned to receive an escalating dose of methotrexate alone or high-dose methotrexate given alongside leucovorin rescue.

In addition, patients with an intermediate or high risk for recurrence were given a prophylactic or therapeutic course of cranial radiotherapy and were further randomly assigned to receive six 5-day courses of nelarabine 650 mg/m2 per day (n=323) or no additional treatment (n=336), the researchers explain.

Among the T-ALL patients with an increased risk for recurrence, disease-free survival was 88.9% for the nelarabine-treated individuals versus 83.3% for controls, the team will report.

Although the A-LLy patients did not show a significant DFS or OS benefit with receipt of nelarabine, the team emphasizes that over 85% of patients achieved 4-year DFS.

Dunsmore also noted that the escalating methotrexate regimen was associated with a better 4-year DFS rate than high-dose methotrexate (89.8 vs 78.0%).

And 4-year DFS rate rose to 92.2% for the T-ALL patients given both nelarabine and an escalating dose of methotrexate.

All patients who did not achieve remission during induction chemotherapy were given nelarabine plus high-dose methotrexate, with 54.8% of these patients achieving 4-year DFS.

The authors describe this as a “significant improvement”, noting that previously just 20% of T-ALL patients who did not achieve cancer remission would be expected to live for another 3 years.

By Lynda Williams

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