Nelarabine in newly diagnosed paediatric T-cell malignancies

Published: 2 Jun 2018

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Dr Kimberly Dunsmore - University of Virginia School of Medicine, Virginia, USA

Dr Dunsmore speaks with ecancer at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting about the use of nelarabine in new cases of paediatric T cell malignancies.

She describes the structure of the COG AALL0434 trial, with almost 2,000 patients randomised to receive escalating dose methotrexate without leucovorin rescue pegaspargase (CMTX) or High Dose MTX (HDMTX) leucovorin rescue, and intermediate and high-risk patients with T-ALL and T-LL were randomised to receive six 5-day courses of nelarabine.

Nelarabine was found to improve DFS for children and young adults with T-ALL, leading Dr Dunsmore to encourage its use as a new standard of care for this population

ecancer's filming has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

AALL0434 is a phase III trial and the largest trial looking at treatment for T-cell malignancy in children and young adults. It is a study in which case we are asking two questions: one, whether nelarabine, which is a new agent for T-cell and T-cell specific, is effective and safe for patients with T-cell leukaemia and lymphoma. The second question was whether methotrexate should be given as high dose inpatient in a hospital setting or as escalating dose in an outpatient setting.

The study enrolled 1,795 patients; it had 1,545 T-cell leukaemia patients and 277 T-cell lymphoma patients. We found that we had the best reported overall survival for T-cell leukaemia patients at 90% at four years, event free survival was 84% at four years. We also found that nelarabine improved the disease free survival for those patients with leukaemia. Those who received nelarabine had an event free survival of 88% versus those who did not who had an event free survival of 83%.

Patients who had the best event free survival were those that received escalating dose methotrexate plus nelarabine - their event free survival was 91% at four years. It’s important to note that there were fewer CNS relapses on the nelarabine arms. Of special importance is the fact that patients who were expected to do the most poorly, those who failed to achieve remission at the end of 29 days of induction, induction failure patients, who historically have a disease free survival of about 19% had an event free survival of 55%. Those patients who had T-cell lymphoma and were at high risk did not seem to have an advantage in using nelarabine as their event free survival was 85% compared to 89% without nelarabine, however, those were very low patient numbers and the arms were not powered to detect a difference.

Out of all of that it sounds like very compelling evidence for the use of nelarabine for these patients.

It is. It’s very exciting to have such an effective treatment for children and young adults with T-cell malignancy.

Is there anything regarding toxicity that might cause you to hesitate in prescribing?

Yes, nelarabine was noted to have some problems with neurotoxicity in previous trials, however, we found that there were no differences and very small amounts of neurotoxicity on this trial. Across all arms it was between 6-9%.

Which I suppose leaves nelarabine as highly recommended, if not a new standard.

I would agree with that.