2018 ASCO: Adding Nelarabine to Standard Chemotherapy Improves Survival in Children and Young Adults With T-Cell Cancers


Key Points

  • Overall, 90.2% of patients treated in this study lived at least 4 years, and 84.3% had no sign of cancer at 4 years.
  • Among patients who had an increased risk of T-ALL recurrence, 88.9% of those who received nelarabine were leukemia-free at 4 years compared to 83.3% of patients who did not receive nelarabine.
  • While patients with T-LL did not benefit from the addition of nelarabine, more than 85% lived for 4 years without signs of disease.
  • Patients with T-ALL who did not have cancer remissions following induction chemotherapy were assigned to receive high-dose methotrexate and nelarabine; 54.8% survived 4 years with no signs of disease, which is a significant improvement. 

A large randomized phase III clinical trial by the Children’s Oncology Group (COG) investigating the safety and efficacy of adding nelarabine (Arranon) to COG-augmented Berlin-Frankfurt-Munster chemotherapy (aBFM) to treat newly diagnosed patients with T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LL) found the combination therapy improved disease-free survival in these patients. Overall, 90.2% of patients lived at least 4 years, and 84.3% had no sign of cancer at 4 years.

In addition, the addition of nelarabine to standard chemotherapy provided further benefit for a group of patients with moderate or high risk of T-ALL recurrence. At 4 years, 89% of the patients who received nelarabine were leukemia-free vs 83% of those who did not. The study was presented during a press briefing in advance of the upcoming 2018 ASCO Annual Meeting and will be reported by Dunsmore et al at the meeting (Abstract 10500).

Study Details

From 2007 to 2014, the researchers enrolled 1,895 newly diagnosed patients with either T-ALL (94% of trial participants) or T-LL (6% of participants) into the phase III randomized trial. Patients were aged 1 to 30 years.

The trial included four arms. All patients received the standard, multidrug aBFM chemotherapy regimen. In addition, patients were randomly assigned to receive either escalating-dose methotrexate without leucovorin rescue plus pegaspargase (Oncaspar; CMTX) or high-dose methotrexate (HDMTX) plus leucovorin rescue. Patients with a moderate or high risk of cancer recurrence were also randomly assigned to receive or not receive nelarabine in addition to chemotherapy and cranial irradiation to prevent or treat brain metastases.

For all randomized T-ALL patients, the 4-year disease-free survival and overall survival rates were 84.3% ± 1.1% and 90.2% ± 0.9%. The 4-year disease-free survival rate for T-ALL patients randomized to nelarabine (n = 323) vs no nelarabine (n = 336) was 88.9% ± 2.2% vs 83.3% ± 2.5% (= .0332).

Among T-ALL patients randomized to CMTX, the 4-year disease-free survival rate for nelarabine (n = 147) vs no nelarabine (n = 151) was 92.2% ± 2.8% vs 89.8% ± 3.0% (P = .3825). For those randomized to HDMTX, the 4-year disease-free survival rate was 86.2% ± 3.2% with nelarabine (n = 176) vs 78.0% ± 3.7% without nelarabine (n = 185; = .024).

Differences between disease-free survival rates in a four-arm comparison were highly significant (= .002), with no significant interactions between MTX and nelarabine randomizations (= .41). T-ALL patients with induction failure (n = 43) assigned to HDMTX/nelarabine had a 4-year disease-free survival rate of 54.8% ± 8.9%. 

Nelarabine did not show an advantage for high-risk T-LL patients, with 4-year disease-free survival rates of 85.0% ± 5.6% vs 89.0% ± 4.7% for nelarabine (n = 60) vs no nelarabine (n = 58; = .2788). Overall toxicity and neurotoxicity were acceptable and not significantly different among all four arms. 

“COGAALL0434 is the largest trial ever conducted for newly diagnosed T-ALL and T-LL, and showed outstanding overall outcomes. Nelarabine improves DFS for children and young adults with T-ALL and should become a new standard of care for this population,” concluded the study authors.


“Before [the researchers] embarked on this [study], only about 80% of patients survived 4 or 5 years. This [therapy] improved [survival] by about 10%, and it didn’t have particular side effects,” said ASCO President Bruce E. Johnson, MD, FASCO, during the press briefing. “Moving nelarabine upfront, closer to the initial treatment, improved the outcomes for these patients.”

Author conflict of interest disclosures are available at the end of the study abstract. 

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®.