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Lookup NU author(s): Professor Anthony MoormanORCiD, Melvin JoyORCiD, Dr Amir EnshaeiORCiD, Emerita Professor Christine Harrison, Dr Claire Schwab, Dr Sujith Samarasinghe, Sarah Lawson, Dr Pamela Kearns
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
Background: Patients with acute lymphoblastic leukaemia (ALL) and good risk genetics (GRG - ETV6::RUNX1 or high hyperdiploidy) have a good response to therapy with 95% survival at 10 years. Analysis of the UKALL2003 trial revealed that GRG patients had an excellent outcome even if their end of induction (EOI) MRD was 0.01%-0.1% and that these patients had a low risk of relapse whether they received standard (regimen A/B) or augmented (regimen C) post-induction therapy (JCO 36:34-43). Aims: To determine whether GRG patients treated on UKALL2011 who had intermediate MRD (≥0.005% & <0.1%) at EOI can be spared augmented therapy without comprising outcome. Methods: UKALL2011 recruited newly diagnosed ALL patients aged 1-24 years between 2012-2018. Patients were stratified by NCI risk, genetics and EOI MRD to post-induction therapy: Regimen A [NCI standard risk (SR) and MRD low risk (LR)], Regimen B [NCI high risk (HR) and MRD LR] or Regimen C (genetic HR or MRD risk). MRD LR was classified as <0.005% throughout the trial. Initially MRD risk was classified as ≥0.005% but after December 2015 patients with GRG were classified as MRD intermediate (≥0.005% and <0.01%) or MRD risk (≥0.1%). After central review, 1,252 patients were classified with GRG. 81 patients were excluded from the current analysis: no EOI MRD result (n=48), Down Syndrome (n=14), induction death (n=13) or incomplete data (n=6). We report standard outcome endpoints with survival rates quoted at 5 years. Results: After a median follow-up time of 5.4 years, the survival of the GRG cohort (n=1,171) was 97% (table). Most GRG patients (59%) were MRD LR, assigned standard therapy and had an excellent outcome. Only 3% GRG patients were aged 16-24 years compared with 10% for the trial. 13% of GRG patients were MRD risk and assigned augmented therapy. They had an increased RR (p<0.001) and lower EFS/OS (both p<0.001) compared to MRD LR patients (table). 336 GRG patients had intermediate MRD with 173 (51%) patients receiving augmented therapy and 163 (49%) patients the lower intensity standard therapy. Even though patients were not randomised, the two groups were similar in terms of sex, age, white cell count, MRD and CNS status. Among these patients a total of 37 relapses have been recorded to date and there was no significant difference in RR (p=0.4), EFS (p=0.4), or OS (p=1.0) by treatment received (table). However, the standard group had shorter median follow-up: 4.1 v 7.2 years (p<0.001) and short follow-up post-relapse (median 1 year). Post-induction therapy varied by NCI status, so we compared outcome by NCI risk group. Among GRG patients with intermediate MRD receiving standard therapy, NCI HR patients (n=37) had a significantly increased RR (p=0.003) and lower EFS (p=0.02) but similar OS (p=0.20) compared to NCI SR patients (n=126) which was confirmed by a test for interaction (p<0.05). Although an adverse outcome for NCI HR patients receiving augmented therapy was also observed, the effect was more pronounced amongst those patients receiving standard therapy. Summary/Conclusion: Overall, all patients with GRG treated on UKALL2011 had excellent OS rates. Higher MRD at EOI was associated with inferior outcome even when these patients received augmented post-induction therapy. We provide strong evidence that GRG patients with intermediate MRD who are NCI SR can be spared the significant excess morbidity related to asparaginase, intra-venous methotrexate and vincristine intensification related to augmented post-induction without significantly comprising RR, EFS and OS. However, NCI HR GRG patients should still receive augmented post-induction therapy.
Author(s): Moorman A, Joy M, Enshaei A, Kirkwood AA, Harrison C, Schwab C, Goulden N, Moppett J, Samarasinghe S, Hough R, Rowntree C, Lawson S, Kearns P, Mee J, Vora A
Publication type: Conference Proceedings (inc. Abstract)
Publication status: Published
Conference Name: EHA2024 Hybrid Congress
Year of Conference: 2024
Pages: 670-671
Online publication date: 14/06/2024
Acceptance date: 23/04/2024
Date deposited: 15/08/2025
ISSN: 2572-9241
Publisher: Wiley
URL: https://doi.org/10.1002/hem3.104
DOI: 10.1002/hem3.104
Notes: Abstract number P426
Series Title: HemaSphere
