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. 2023 Sep 1;41(25):4130-4142.
doi: 10.1200/JCO.22.02705. Epub 2023 Jul 17.

Improved Outcome for ALL by Prolonging Therapy for IKZF1 Deletion and Decreasing Therapy for Other Risk Groups

Rob Pieters  1   2 , Hester de Groot-Kruseman  1   2 , Marta Fiocco  1   2   3   4 , Femke Verwer  1   2 , Merian Van Overveld  1 , Edwin Sonneveld  1   2 , Vincent van der Velden  5 , H Berna Beverloo  6 , Marc Bierings  1   2 , Natasja Dors  1 , Valérie de Haas  1   2 , Peter Hoogerbrugge  1 , Inge Van der Sluis  1 , Wim Tissing  1 , Margreet Veening  1 , Judith Boer  1 , Monique Den Boer  1
Affiliations

Improved Outcome for ALL by Prolonging Therapy for IKZF1 Deletion and Decreasing Therapy for Other Risk Groups

Rob Pieters et al. J Clin Oncol. .

Erratum in

Abstract

Purpose: The ALL10 protocol improved outcomes for children with ALL by stratifying and adapting therapy into three minimal residual disease-defined risk groups: standard risk, medium risk (MR), and high risk. IKZF1-deleted (IKZF1del) ALL in the largest MR group still showed poor outcome, in line with protocols worldwide, accounting for a high number of overall relapses. ALL10 showed high toxicity in Down syndrome (DS) and excellent outcome in ETV6::RUNX1 ALL. Poor prednisone responders (PPRs) were treated as high risk in ALL10. In ALL11, we prolonged therapy for IKZF1del from 2 to 3 years. We reduced therapy for DS by omitting anthracyclines completely, for ETV6::RUNX1 in intensification, and for PPR by treatment as MR.

Methods: Eight hundred nineteen patients with ALL (age, 1-18 years) were enrolled on ALL11 and stratified as in ALL10. Results were compared with those in ALL10.

Results: The five-year overall survival (OS), event-free survival (EFS), cumulative risk of relapse (CIR), and death in complete remission on ALL11 were 94.2% (SE, 0.9%), 89.0% (1.2), 8.2% (1.1), and 2.3% (0.6), respectively. Prolonged maintenance for IKZF1del MR improved 5-year CIR by 2.2-fold (10.8% v 23.4%; P = .035) and EFS (87.1% v 72.3%; P = .019). Landmark analysis at 2 years from diagnosis showed a 2.9-fold reduction of CIR (25.6%-8.8%; P = .008) and EFS improvement (74.4%-91.2%; P = .007). Reduced therapy did not abrogate 5-year outcome for ETV6::RUNX1 (EFS, 98.3%; OS, 99.4%), DS (EFS, 87.0%; OS, 87.0%), and PPR (EFS, 81.1%; OS, 94.9%).

Conclusion: Children with IKZF1del ALL seem to benefit from prolonged maintenance therapy. Chemotherapy was successfully reduced for patients with ETV6::RUNX1, DS, and PPR ALL. It has to be noted that these results were obtained in a nonrandomized study using a historical control group.

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