Prognostic impact of TP53 mutation in newly diagnosed diffuse large B-cell lymphoma patients treated in the FIL-DLCL04 trial.
Adult
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Clinical Trials as Topic
Cyclophosphamide
/ therapeutic use
Doxorubicin
/ therapeutic use
Female
Humans
Lymphoma, Large B-Cell, Diffuse
/ diagnosis
Male
Middle Aged
Mutation
Prednisone
/ therapeutic use
Prognosis
Rituximab
/ therapeutic use
Stem Cell Transplantation
Survival Analysis
Treatment Outcome
Tumor Suppressor Protein p53
/ genetics
Vincristine
/ therapeutic use
Young Adult
BCL-2
TP53
haematological malignancy
non-Hodgkin lymphoma
prognostic factors
transplantation
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
03
11
2021
received:
06
09
2021
accepted:
11
11
2021
pubmed:
25
12
2021
medline:
11
3
2022
entrez:
24
12
2021
Statut:
ppublish
Résumé
The prognostic role of TP53 disruption has been established in diffuse large B-cell lymphoma (DLBCL). Aim of this analysis was to correlate TP53 mutations by Sanger sequencing, cell of origin (COO) profile by Lymph2Cx panel on the NanoString platform and MYC, BCL2 and BCL6 overexpression or re-arrangements by immunohistochemistry (IHC) and fluorescent in-situ hybridization (FISH), with outcome in DLBCL patients enrolled into the FIL-DLCL04 trial (NCT00499018). One hundred and twenty-five DLBCL patients with tumour block available were analyzed. TP53 was mutated in 11/125 (9%) cases; 60/125 patients received high-dose chemoimmunotherapy up-front, as for the randomization arm; COO was reported in 88 patients: 48 germinal centre B-cell like, 25 activated B-cell like and 17 unclassified; 26 patients were double expressors in IHC and 11 double hit in FISH. After a median follow-up of 72 months, five-year failure-free survival (FFS) for TP53 mutated versus wild-type was 24% and 72%, and five-year overall survival (OS) was 34% and 83%, respectively. Adjusted hazard ratio (HR) was 2·28 [95% confidence interval (CI) 0·89-5·86, p = 0·086] and 4·05 (95% CI 1·37-11·97, p = 0·011) for FFS and OS, respectively. In this series of young DLBCL patients, TP53 gene mutation identified a poor prognosis subgroup, regardless of treatment and other biological markers.
Substances chimiques
R-CHOP protocol
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Rituximab
4F4X42SYQ6
Vincristine
5J49Q6B70F
Doxorubicin
80168379AG
Cyclophosphamide
8N3DW7272P
Prednisone
VB0R961HZT
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1184-1193Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021 British Society for Haematology and John Wiley & Sons Ltd.
Références
Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood. 2010;116(12):2040-5.
Ziepert M, Hasenclever D, Kuhnt E, Glass B, Schmitz N, Pfreundschuh M, et al. Standard International prognostic index remains a valid predictor of outcome for patients with aggressive CD20+ B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(14):2373-80.
Chiappella A, Martelli M, Angelucci E, Brusamolino E, Evangelista A, Carella AM, et al. Rituximab-dose-dense chemotherapy with or without high-dose chemotherapy plus autologous stem-cell transplantation in high-risk diffuse large B-cell lymphoma (DLCL04): final results of a multicentre, open-label, randomised, controlled, phase 3 study. Lancet Oncol. 2017;18(8):1076-88.
Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, et al. Autologous transplantation as consolidation for aggressive non-Hodgkin’s lymphoma. N Engl J Med. 2013;369(18):1681-90.
Schmitz N, Nickelsen M, Ziepert M, Haenel M, Borchmann P, Schmidt C, et al. Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1). Lancet Oncol. 2012;13(12):1250-9.
Cortelazzo S, Tarella C, Gianni AM, Ladetto M, Barbui AM, Rossi A, et al. Randomized trial comparing R-CHOP versus high-dose sequential chemotherapy in high-risk patients with diffuse large B-cell lymphomas. J Clin Oncol. 2016;34(33):4015-22.
Le Gouill S, Milpied NJ, Lamy T, Delwail V, Gressin R, Guyotat D, et al. First-line rituximab (R) high-dose therapy (R-HDT) versus R-CHOP14 for young adults with diffuse large B-cell lymphoma: preliminary results of the GOELAMS 075 prospective multicenter randomized trial. J Clin Oncol. 2011;29(15_suppl):8003.
Lenz G, Wright GW, Emre NCT, Kohlhammer H, Dave SS, Davis RE, et al. Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. Proc Natl Acad Sci U S A. 2008;105(36):13520-5.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th Edition. Lyon: IARC Press; 2017. https://publications.iarc.fr/Book-And-Report-Series/Who-Classification-Of-Tumours/WHO-Classification-Of-Tumours-Of-Haematopoietic-And-Lymphoid-Tissues-2017
Cheung K-JJ, Horsman DE, Gascoyne RD. The significance of TP53 in lymphoid malignancies: mutation prevalence, regulation, prognostic impact and potential as a therapeutic target. Br J Haematol. 2009;146(3):257-69.
Halldórsdóttir AM, Lundin A, Murray F, Mansouri L, Knuutila S, Sundström C, et al. Impact of TP53 mutation and 17p deletion in mantle cell lymphoma. Leukemia. 2011;25(12):1904-8.
Nordström L, Sernbo S, Eden P, Grønbaek K, Kolstad A, Räty R, et al. SOX11 and TP53 add prognostic information to MIPI in a homogenously treated cohort of mantle cell lymphoma-a Nordic Lymphoma Group study. Br J Haematol. 2014;166(1):98-108.
Lo Coco F, Gaidano G, Louie DC, Offit K, Chaganti RS, Dalla-Favera R, et al. p53 mutations are associated with histologic transformation of follicular lymphoma. Blood. 1993;82(8):2289-95.
O'Shea D, O'Riain C, Taylor C, Waters R, Carlotti E, MacDougall F, et al. The presence of TP53 mutation at diagnosis of follicular lymphoma identifies a high-risk group of patients with shortened time to disease progression and poorer overall survival. Blood. 2008;112(8):3126-9.
Leroy K, Haioun C, Lepage E, Le Métayer N, Berger F, Labouyrie E, et al. p53 gene mutations are associated with poor survival in low and low-intermediate risk diffuse large B-cell lymphomas. Ann Oncol. 2002;13(7):1108-15.
Young KH, Weisenburger DD, Dave BJ, Smith L, Sanger W, Iqbal J, et al. Mutations in the DNA-binding codons of TP53, which are associated with decreased expression of TRAILreceptor-2, predict for poor survival in diffuse large B-cell lymphoma. Blood. 2007;110(13):4396-405.
Zainuddin N, Berglund M, Wanders A, Ren ZP, Amini RM, Lindell M, et al. TP53 mutations predict for poor survival in de novo diffuse large B-cell lymphoma of germinal center subtype. Leuk Res. 2009;33(1):60-6.
Xu-Monette ZY, Wu L, Visco C, Tai YC, Tzankov A, Liu W-M, et al. Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP: report from an International DLBCL Rituximab-CHOP Consortium Program Study. Blood. 2012;120(19):3986-96.
Zenz T, Kreuz M, Fuge M, Klapper W, Horn H, Staiger AM, et al. TP53 mutation and survival in aggressive B cell lymphoma. Int J Cancer. 2017;141(7):1381-8.
Young KH, Leroy K, Møller MB, Colleoni GWB, Sánchez-Beato M, Kerbauy FR, et al. Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma: an international collaborative study. Blood. 2008;112(8):3088-98.
Scott DW, Wright GW, Williams PM, Lih C-J, Walsh W, Jaffe ES, et al. Determining cell-of-origin subtypes of diffuse large B-cell lymphoma using gene expression in formalin-fixed paraffin-embedded tissue. Blood. 2014;123(8):1214-7.
Stilgenbauer S, Schnaiter A, Paschka P, Zenz T, Rossi M, Döhner K, et al. Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial. Blood. 2014;123(21):3247-54.
Dodero A, Guidetti A, Marino F, Tucci A, Barretta F, Re A, et al. Dose-Adjusted Epoch and Rituximab for the treatment of double expressor and double hit diffuse large B-cell lymphoma: impact of TP53 mutations on clinical outcome. Haematologica. 2020. https://doi.org/10.3324/haematol.2021.278638
Yemelyanova A, Vang R, Kshirsagar M, Lu D, Marks MA, Shih IM, et al. Immunohistochemical staining patterns of p53 can serve as a surrogate marker for TP53 mutations in ovarian carcinoma: an immunohistochemical and nucleotide sequencing analysis. Mod Pathol. 2011;24(9):1248-53.
Lepelley P, Preudhomme C, Vanrumbeke M, Quesnel B, Cosson A, Fenaux P. Detection of p53 mutations in hematological malignancies: comparison between immunocytochemistry and DNA analysis. Leukemia. 1994;8(8):1342-9.
Zenz T, Kröber A, Scherer K, Häbe S, Bühler A, Benner A, et al. Monoallelic TP53 inactivation is associated with poor prognosis in chronic lymphocytic leukemia: results from a detailed genetic characterization with long-term follow-up. Blood. 2008;112(8):3322-9.
Younes A, Sehn LH, Johnson P, Zinzani PL, Hong X, Zhu J, et al. Randomized phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non-germinal center B-cell diffuse large B-cell lymphoma. J Clin Oncol. 2019;37(15):1285-95.
Nowakowski G, Chiappella A, Witzig TE, Spina M Gascoyne R, Zhang L, et al. ROBUST: a phase III study of lenalidomide plus R-CHOP versus placebo plus R-CHOP in previously untreated patients with ABC-type diffuse large B-cell lymphoma. J Clin Oncol. 2021;39(12):1317-28.
Zelenetz AD, Salles G, Mason KD, Casulo C, Le Gouill S, Sehn LH, et al. Venetoclax plus R- or G-CHOP in non-Hodgkin lymphoma: results from the CAVALLI phase 1b trial. Blood. 2019;133(18):1964-76.
Morschhauser F, Feugier P, Flinn IW, Gasiorowski R, Greil R, Illés Á, et al. A phase 2 study of venetoclax plus R-CHOP as first-line treatment for patients with diffuse large B-cell lymphoma. Blood. 2021;137(5):600-9.
Chapuy B, Stewart C, Dunford AJ, Kim J, Kamburov A, Redd RA, et al. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat Med. 2018;24(5):679-90.
Schmitz R, Wright GW, Huang DW, et al. Genetics and pathogenesis of diffuse large B-cell lymphoma. N Engl J Med. 2018;378(15):1396-407.
Ciavarella S, Vegliante MC, Fabbri M, De Summa S, Melle F, Motta G, et al. Dissection of DLBCL microenvironment provides a gene expression-based predictor of survival applicable to formalin-fixed paraffin-embedded tissue. Ann Oncol. 2018;29(12):2363-70.
Derenzini E, Agostinelli C, Rossi A, Rossi M, Scellato F, Melle F, et al. Genomic alterations of ribosomal protein genes in diffuse large B cell lymphoma. Br J Haematol. 2019;185(2):330-4.