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Article Dans Une Revue Blood Année : 2023

Genetic alterations and MRD refine risk assessment within KMT2A -rearranged B-cell precursor ALL in adult: a GRAALL study

Lise Larcher
Marie Passet
Susanne Kubetzko
Rolf Marschalek
Marina Lafage-Pochitaloff
Michael Baumann
  • Fonction : Auteur
Nicolas Boissel

Résumé

KMT2A-rearranged (KMT2A-r) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is widely recognized as a high-risk leukemia in both children and adults. However, there is a paucity of data on adults treated in recent protocols and the optimal treatment strategy for these patients is still a matter of debate. In this study, we set out to refine the prognosis of adult KMT2A-r BCP-ALL treated with modern chemotherapy regimen and investigate the prognostic impact of co-mutations and minimal residual disease (MRD). Of 1091 adult patients with Philadelphia-negative BCP-ALL enrolled in three consecutive GRAALL trials, 141 (12.9%) had KMT2A-r, with 5-year cumulative incidence of relapse (CIR) and overall survival (OS) rates of 40.7% and 53.3%, respectively. Molecular profiling highlighted a low mutational burden in this subtype, reminiscent of infant BCP-ALL. However, the presence of TP53 and/or IKZF1 alterations defined a subset of patients with significantly poorer CIR (69.3% vs 36.2%, p=0.001) and OS (28.1% vs 60.7%, p=0.006). We next analyzed the prognostic implication of MRD measured after induction and first consolidation, using both immunoglobulin (IG)/T-cell receptor (TR) rearrangements and KMT2A genomic fusion as markers. In approximately one third of patients, IG/TR rearrangements were absent or displayed clonal evolution during the disease course, compromising MRD monitoring. By contrast, KMT2A-based MRD was highly reliable and was strongly associated with outcome, with early good responders having an excellent outcome (3-year CIR 7.1% and OS 92.9%). Altogether, our study reveals striking heterogeneity in outcomes within adults with KMT2A-r BCP-ALL and provides new biomarkers to guide risk-based therapeutic stratification.
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Dates et versions

hal-04244336 , version 1 (08-12-2023)

Licence

Paternité - Pas d'utilisation commerciale

Identifiants

Citer

Rathana Kim, Hugo Bergugnat, Cedric Pastoret, Florence Pasquier, Emmanuel Raffoux, et al.. Genetic alterations and MRD refine risk assessment within KMT2A -rearranged B-cell precursor ALL in adult: a GRAALL study. Blood, 2023, 142 (21), pp.1806-1817. ⟨10.1182/blood.2023021501⟩. ⟨hal-04244336⟩
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