Among young patients with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL), nelarabine was found to improve disease-free survival (DFS) when given with the augmented Berlin-Frankfurt-Muenster (ABFM) treatment regimen, according to results of a phase 3 clinical trial published in the Journal of Clinical Oncology.

The Children’s Oncology Group AALL0434 trial ( Identifier: NCT00408005) evaluated patients with newly diagnosed T-ALL who were aged 1 to 31 years. Patients were treated with the ABFM regimen and were randomly assigned to receive either escalating-dose methotrexate (MTX) with pegaspargase (C-MTX) or high-dose MTX (HDMTX). A further randomization was applied to patients at high or intermediate risk, which either included or excluded further treatment with 6 courses of nelarabine.

The 5-year DFS rate across the entire study population (1562 patients) was 83.7%, with a 5-year overall survival (OS) rate of 89.5%.

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A total of 323 patients received nelarabine, and 336 did not. The 5-year rate of DFS was 88.2% for patients who were treated with nelarabine, compared with 82.1% for those who were not (P =.029). With nelarabine, the 5-year OS was 90.3%, and it was 87.9% without nelarabine (P =.168).

The treatment arm that showed the greatest performance in this study consisted of C-MTX with nelarabine, and this group (147 patients) had a 5-year DFS rate of 91.4%. In addition, the 5-year DFS rates for C-MTX without nelarabine, HDMTX with nelarabine, and HDMTX without nelarabine were 87.2%, 85.5%, and 78.1%, respectively.

The 5-year cumulative incidence of central nervous system (CNS) relapse was 1.3% for patients treated with nelarabine, compared with 6.9% in patients without nelarabine (P =.0001).

Treatment arms reportedly showed similar adverse event (AE) profiles, including rates of neurotoxicity. Nontargeted grade 3 or higher AEs occurred at rates of 41.2% with nelarabine and 46.1% without it. Rates of targeted grade 3 to 4 peripheral neurotoxicities were similar with or without nelarabine, as were rates of grade 3 to 5 central neurotoxicities. There were 2 deaths among patients in the HDMTX plus nelarabine arm who were reported to have experienced central neurocognitive decompensation.

“In summary, the addition of nelarabine decreased CNS relapses and improved overall DFS, especially for patients with higher-risk disease, independent of age or race,” concluded the investigators.


Dunsmore KP, Winter SS, Devidas M, et al. Children’s Oncology Group AALL0434: a phase III randomized clinical trial testing nelarabine in newly diagnosed T-cell acute lymphoblastic leukemia. J Clin Oncol. Published online August 19, 2020. doi:10.1200/JCO.20.00256