Titre
Significance of Measurable Residual Disease in Adult Philadelphia Chromosome-Positive ALL: A GRAAPH-2014 Study.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Kim, R.
Auteure/Auteur
Chalandon, Y.
Auteure/Auteur
Rousselot, P.
Auteure/Auteur
Cayuela, J.M.
Auteure/Auteur
Huguet, F.
Auteure/Auteur
Balsat, M.
Auteure/Auteur
Passet, M.
Auteure/Auteur
Chevallier, P.
Auteure/Auteur
Hicheri, Y.
Auteure/Auteur
Raffoux, E.
Auteure/Auteur
Leguay, T.
Auteure/Auteur
Chantepie, S.
Auteure/Auteur
Maury, S.
Auteure/Auteur
Hayette, S.
Auteure/Auteur
Solly, F.
Auteure/Auteur
Braun, T.
Auteure/Auteur
De Prijck, B.
Auteure/Auteur
Cacheux, V.
Auteure/Auteur
Salanoubat, C.
Auteure/Auteur
Farnault, L.
Auteure/Auteur
Guibaud, I.
Auteure/Auteur
Lamarque, M.
Auteure/Auteur
Gastaud, L.
Auteure/Auteur
Lemasle, E.
Auteure/Auteur
Brissot, E.
Auteure/Auteur
Tavernier, E.
Auteure/Auteur
Bilger, K.
Auteure/Auteur
Villate, A.
Auteure/Auteur
Soulier, J.
Auteure/Auteur
Graux, C.
Auteure/Auteur
Lhéritier, V.
Auteure/Auteur
Dombret, H.
Auteure/Auteur
Boissel, N.
Auteure/Auteur
Clappier, E.
Auteure/Auteur
Liens vers les unités
ISSN
1527-7755
Statut éditorial
Publié
Date de publication
2024-09-10
Volume
42
Numéro
26
Première page
3140
Dernière page/numéro d’article
3150
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
BCR::ABL1 quantification is widely regarded as the standard for monitoring measurable residual disease (MRD) in Philadelphia chromosome-positive (Ph+) ALL. However, recent evidence of BCR::ABL1 multilineage involvement questions the significance of BCR::ABL1 MRD. We aimed to define the prognostic role of MRD as assessed by BCR::ABL1 or lymphoid-specific immunoglobulin/T-cell receptor (IG/TR) gene markers.
We conducted BCR::ABL1 and IG/TR quantification after each treatment cycle in 264 patients treated in the GRAAPH-2014 trial, which used four cycles of reduced-intensity chemotherapy with nilotinib, followed by hematopoietic stem-cell transplantation (HSCT).
Comparing BCR::ABL1 and IG/TR MRD revealed residual BCR::ABL1-positive non-ALL cells in 98 (43%) of 228 patients, defining multilineage Ph+ ALL. Despite poorer BCR::ABL1 responses, patients with multilineage Ph+ ALL had similar disease-free survival (DFS; hazard ratio [HR], 0.83 [95% CI, 0.49 to 1.41]; P = .50). Although BCR::ABL1 response failed to predict outcomes, IG/TR positivity (≥0.01%) was strongly associated with lower DFS (after cycle 2, HR, 2.49 [95% CI, 1.40 to 4.40]; P = .002; after cycle 4, HR, 4.13 [95% CI, 1.82 to 9.38]; P = .001). In multivariable analysis, both IG/TR positivity after cycle 2 and initial WBC count ≥30 × 10 <sup>9</sup> /L predicted poorer DFS, enabling to define a high-risk group having a 4-year DFS of 56.5% compared with 87.6% (HR, 3.72 [95% CI, 1.93 to 7.15]; P < .001). Moreover, allogeneic HSCT significantly improved DFS in the high-risk group (HR, 0.33 [95% CI, 0.18 to 0.60]; P < .001), whereas the standard-risk group had favorable outcomes regardless of allogeneic HSCT.
Our findings challenge the significance of BCR::ABL1 monitoring in adult Ph+ ALL and demonstrate the prognostic role of IG/TR MRD. This study provides a framework for using MRD to guide treatment strategies in adults with Ph+ ALL.
We conducted BCR::ABL1 and IG/TR quantification after each treatment cycle in 264 patients treated in the GRAAPH-2014 trial, which used four cycles of reduced-intensity chemotherapy with nilotinib, followed by hematopoietic stem-cell transplantation (HSCT).
Comparing BCR::ABL1 and IG/TR MRD revealed residual BCR::ABL1-positive non-ALL cells in 98 (43%) of 228 patients, defining multilineage Ph+ ALL. Despite poorer BCR::ABL1 responses, patients with multilineage Ph+ ALL had similar disease-free survival (DFS; hazard ratio [HR], 0.83 [95% CI, 0.49 to 1.41]; P = .50). Although BCR::ABL1 response failed to predict outcomes, IG/TR positivity (≥0.01%) was strongly associated with lower DFS (after cycle 2, HR, 2.49 [95% CI, 1.40 to 4.40]; P = .002; after cycle 4, HR, 4.13 [95% CI, 1.82 to 9.38]; P = .001). In multivariable analysis, both IG/TR positivity after cycle 2 and initial WBC count ≥30 × 10 <sup>9</sup> /L predicted poorer DFS, enabling to define a high-risk group having a 4-year DFS of 56.5% compared with 87.6% (HR, 3.72 [95% CI, 1.93 to 7.15]; P < .001). Moreover, allogeneic HSCT significantly improved DFS in the high-risk group (HR, 0.33 [95% CI, 0.18 to 0.60]; P < .001), whereas the standard-risk group had favorable outcomes regardless of allogeneic HSCT.
Our findings challenge the significance of BCR::ABL1 monitoring in adult Ph+ ALL and demonstrate the prognostic role of IG/TR MRD. This study provides a framework for using MRD to guide treatment strategies in adults with Ph+ ALL.
Sujets
PID Serval
serval:BIB_EBFCC8A4EE87
PMID
Date de création
2024-07-26T12:20:36.103Z
Date de création dans IRIS
2025-05-21T05:50:34Z