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The potential prognostic influence of genetic aberrations on chronic lymphocytic leukaemia (CLL) can vary based on various factors, such as the immunoglobulin heavy variable (IGHV) status. We conducted an integrative analysis on genetic abnormalities identified through cytogenetics and targeted next-generation sequencing in 536 CLL patients receiving first-line chemo(immuno)therapies (CIT) as part of two prospective trials. We evaluated the prognostic implications of the main abnormalities, with specific attention to their relative impact according to IGHV status. In the entire cohort, unmutated (UM)-IGHV, complex karyotype, del(11q) and ATM mutations correlated significantly with shorter progression-free survival (PFS). Focusing on the subset of mutated IGHV (M-IGHV) patients, univariate analysis showed that complex karyotype, del(11q), SF3B1 and SAMHD1 mutations were associated with significant lower PFS. The prognostic influence varied based on the patient's IGHV status, as these abnormalities did not affect outcomes in the UM-IGHV subgroup. TP53 mutations had no significant impact on outcomes in the M-IGHV subgroup. Our findings highlight the diverse prognostic influence of genetic aberrations depending on the IGHV status in symptomatic CLL patients receiving first-line CIT. The prognosis of gene mutations and cytogenetic abnormalities needs to be investigated with a compartmentalized methodology, taking into account the IGVH status of patients receiving first-line BTK and/or BCL2 inhibitors.

Titel:	Prognostic impact of genetic abnormalities in 536 first-line chronic lymphocytic leukaemia patients without 17p deletion treated with chemoimmunotherapy in two prospective trials: Focus on IGHV-mutated subgroups (a FILO study).
Autor/in / Beteiligte Person:	Nguyen-Khac, F ; Baron, M ; Guièze, R ; Feugier, P ; Fayault, A ; Raynaud, S ; Troussard, X ; Droin, N ; Damm, F ; Smagghe, L ; Susin, S ; Leblond, V ; Dartigeas, C ; Van den Neste, E ; Leprêtre, S ; Bernard, OA ; Roos-Weil, D
Link:	Full Text Finder (Volltext)
Zeitschrift:	British journal of haematology, 2024-04-23
Veröffentlichung:	Ahead of Print, 2024
Medientyp:	academicJournal
ISSN:	1365-2141 (electronic)
DOI:	10.1111/bjh.19459
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Corporate Authors: on behalf the FILO (French Innovative Leukaemia Organization) Group Publication Type: Journal Article Language: English [Br J Haematol] 2024 Apr 23. <i>Date of Electronic Publication: </i>2024 Apr 23. References: Lazarian G, Guièze R, Wu CJ. Clinical implications of novel genomic discoveries in chronic lymphocytic leukemia. J Clin Oncol. 2017;35:984–993. ; Blakemore SJ, Clifford R, Parker H, Antoniou P, Stec‐Dziedzic E, Larrayoz M, et al. Clinical significance of TP53, BIRC3, ATM and MAPK‐ERK genes in chronic lymphocytic leukaemia: data from the randomised UK LRF CLL4 trial. Leukemia. 2020;34:1760–1774. ; Knisbacher BA, Lin Z, Hahn CK, Nadeu F, Duran‐Ferrer M, Stevenson KE, et al. Molecular map of chronic lymphocytic leukemia and its impact on outcome. Nat Genet. 2022;54:1664–1674. ; Mansouri L, Thorvaldsdottir B, Sutton L‐A, Karakatsoulis G, Meggendorfer M, Parker H, et al. Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY. Leukemia. 2023;37:339–347. ; Nadeu F, Delgado J, Royo C, Baumann T, Stankovic T, Pinyol M, et al. Clinical impact of clonal and subclonal TP53, SF3B1, BIRC3, NOTCH1, and ATM mutations in chronic lymphocytic leukemia. Blood. 2016;127:2122–2130. ; Shadman M. Diagnosis and treatment of chronic lymphocytic leukemia: a review. JAMA. 2023;329:918–932. ; Davids MS, Brander DM, Kim HT, Tyekucheva S, Bsat J, Savell A, et al. Ibrutinib plus fludarabine, cyclophosphamide, and rituximab as initial treatment for younger patients with chronic lymphocytic leukaemia: a single‐arm, multicentre, phase 2 trial. Lancet Haematol. 2019;6:e419–e428. ; Jain N, Thompson P, Burger J, Ferrajoli A, Takahashi K, Estrov Z, et al. Ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab (iFCG) regimen for chronic lymphocytic leukemia (CLL) with mutated IGHV and without TP53 aberrations. Leukemia. 2021;35:3421–3429. ; Michallet A‐S, Letestu R, Le Garff‐Tavernier M, Campos L, Ticchioni M, Dilhuydy M‐S, et al. A fixed‐duration immunochemotherapy approach in CLL: 5.5‐year results from the phase 2 ICLL‐07 FILO trial. Blood Adv. 2023;7:3936–3945. ; Dartigeas C, Van Den Neste E, Léger J, Maisonneuve H, Berthou C, Dilhuydy M‐S, et al. Rituximab maintenance versus observation following abbreviated induction with chemoimmunotherapy in elderly patients with previously untreated chronic lymphocytic leukaemia (CLL 2007 SA): an open‐label, randomised phase 3 study. Lancet Haematol. 2018;5:e82–e94. ; Lepretre S, Aurran T, Mahé B, Cazin B, Tournilhac O, Maisonneuve H, et al. Excess mortality after treatment with fludarabine and cyclophosphamide in combination with alemtuzumab in previously untreated patients with chronic lymphocytic leukemia in a randomized phase 3 trial. Blood. 2012;119:5104–5110. ; Hallek M, Cheson BD, Catovsky D, Caligaris‐Cappio F, Dighiero G, Döhner H, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131:2745–2760. ; International Standing Committee on Human Cytogenetic Nomenclature. ISCN: an international system for human cytogenomic nomenclature. Basel, NY: Karger; 2020. ; Damm F, Mylonas E, Cosson A, Yoshida K, Della Valle V, Mouly E, et al. Acquired initiating mutations in early hematopoietic cells of CLL patients. Cancer Discov. 2014;4:1088–1101. ; Rossi D, Rossi D, Khiabanian H, Spina V, Ciardullo C, Bruscaggin A, et al. Clinical impact of small TP53 mutated subclones in chronic lymphocytic leukemia. Blood. 2014;123:2139–2147. ; Baliakas P, Hadzidimitriou A, Sutton L‐A, Rossi D, Minga E, Villamor N, et al. Recurrent mutations refine prognosis in chronic lymphocytic leukemia. Leukemia. 2015;29:329–336. ; Rossi D, Bruscaggin A, Spina V, Rasi S, Khiabanian H, Messina M, et al. Mutations of the SF3B1 splicing factor in chronic lymphocytic leukemia: association with progression and fludarabine‐refractoriness. Blood. 2011;118:6904–6908. ; Rossi D, Rasi S, Spina V, Bruscaggin A, Monti S, Ciardullo C, et al. Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia. Blood. 2013;121:1403–1412. ; Spunarova M, Tom N, Pavlova S, Mraz M, Brychtova Y, Doubek M, et al. Impact of gene mutations and chromosomal aberrations on progression‐free survival in chronic lymphocytic leukemia patients treated with front‐line chemoimmunotherapy: clinical practice experience. Leuk Res. 2019;81:75–81. ; Tausch E, Beck P, Schlenk RF, Jebaraj BJ, Dolnik A, Yosifov DY, et al. Prognostic and predictive role of gene mutations in chronic lymphocytic leukemia: results from the pivotal phase III study COMPLEMENT1. Haematologica. 2020a;105:2440–2447. ; Baliakas P, Moysiadis T, Hadzidimitriou A, Xochelli A, Jeromin S, Agathangelidis A, et al. Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia. Haematologica. 2019;104:360–369. ; Jeromin S, Weissmann S, Haferlach C, Dicker F, Bayer K, Grossmann V, et al. SF3B1 mutations correlated to cytogenetics and mutations in NOTCH1, FBXW7, MYD88, XPO1 and TP53 in 1160 untreated CLL patients. Leukemia. 2014;28:108–117. ; Puente XS, Beà S, Valdés‐Mas R, Villamor N, Gutiérrez‐Abril J, Martín‐Subero JI, et al. Non‐coding recurrent mutations in chronic lymphocytic leukaemia. Nature. 2015;526:519–524. ; Jaramillo S, Agathangelidis A, Schneider C, Bahlo J, Robrecht S, Tausch E, et al. Prognostic impact of prevalent chronic lymphocytic leukemia stereotyped subsets: analysis within prospective clinical trials of the German CLL study group (GCLLSG). Haematologica. 2020;105:2598–2607. ; Griffin R, Wiedmeier‐Nutor JE, Parikh SA, McCabe CE, O'Brien DR, Boddicker NJ, et al. Differential prognosis of single and multiple TP53 abnormalities in high‐count MBL and untreated CLL. Blood Adv. 2023;7:3169–3179. ; Malcikova J, Smardova J, Rocnova L, Tichy B, Kuglik P, Vranova V, et al. Monoallelic and biallelic inactivation of TP53 gene in chronic lymphocytic leukemia: selection, impact on survival, and response to DNA damage. Blood. 2009;114:5307–5314. ; Barr PM, Owen C, Robak T, Tedeschi A, Bairey O, Burger JA, et al. Up to 8‐year follow‐up from RESONATE‐2: first‐line ibrutinib treatment for patients with chronic lymphocytic leukemia. Blood Adv. 2022;6:3440–3450. ; Tausch E, Schneider C, Robrecht S, Zhang C, Dolnik A, Bloehdorn J, et al. Prognostic and predictive impact of genetic markers in patients with CLL treated with obinutuzumab and venetoclax. Blood. 2020b;135:2402–2412. ; Brieghel C, Aarup K, Torp MH, Andersen MA, Yde CW, Tian X, et al. Clinical outcomes in patients with multi‐hit TP53 chronic lymphocytic leukemia treated with ibrutinib. Clin Cancer Res. 2021;27:4531–4538. ; Fürstenau M, Thus YJ, Robrecht S, Mellink CHM, van der Kevie‐Kersemaekers A‐M, Dubois J, et al. High karyotypic complexity is an independent prognostic factor in patients with CLL treated with venetoclax combinations. Blood. 2023;142:446–459. Grant Information: Institut National du Cancer (INCA); ITMO Cancer AVIESAN Contributed Indexing: Keywords: CLL; IGHV; cytogenetic abnormalities; mutations; prognosis Entry Date(s): Date Created: 20240424 Latest Revision: 20240424 Update Code: 20240425

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Prognostic impact of genetic abnormalities in 536 first-line chronic lymphocytic leukaemia patients without 17p deletion treated with chemoimmunotherapy in two prospective trials: Focus on IGHV-mutated subgroups (a FILO study).