Detailed Information on Publication Record
2021
Low-burden TP53 mutations in CLL: clinical impact and clonal evolution within the context of different treatment options
MALČÍKOVÁ, Jitka, Šárka PAVLOVÁ, Barbara KUNT VONKOVÁ, Lenka RADOVÁ, Karla PLEVOVÁ et. al.Basic information
Original name
Low-burden TP53 mutations in CLL: clinical impact and clonal evolution within the context of different treatment options
Authors
MALČÍKOVÁ, Jitka (203 Czech Republic, belonging to the institution), Šárka PAVLOVÁ (203 Czech Republic, belonging to the institution), Barbara KUNT VONKOVÁ (203 Czech Republic, belonging to the institution), Lenka RADOVÁ (203 Czech Republic, belonging to the institution), Karla PLEVOVÁ (203 Czech Republic, belonging to the institution), Jana KOTAŠKOVÁ (203 Czech Republic, belonging to the institution), Karol PÁL (703 Slovakia, belonging to the institution), Barbara DVOŘÁČKOVÁ (203 Czech Republic, belonging to the institution), Marcela ŽENATOVÁ (203 Czech Republic, belonging to the institution), Jakub HYNŠT (203 Czech Republic, belonging to the institution), Eva ONDROUŠKOVÁ (203 Czech Republic, belonging to the institution), Anna PANOVSKÁ (203 Czech Republic, belonging to the institution), Yvona BRYCHTOVÁ (203 Czech Republic, belonging to the institution), Kristýna ZÁVACKÁ (203 Czech Republic, belonging to the institution), Boris TICHÝ (203 Czech Republic, belonging to the institution), Nikola TOM (203 Czech Republic, belonging to the institution), Jiří MAYER (203 Czech Republic, belonging to the institution), Michael DOUBEK (203 Czech Republic, belonging to the institution) and Šárka POSPÍŠILOVÁ (203 Czech Republic, guarantor, belonging to the institution)
Edition
Blood, Washington DC, USA, American Society of Hematology, 2021, 0006-4971
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
30205 Hematology
Country of publisher
United States of America
Confidentiality degree
není předmětem státního či obchodního tajemství
References:
Impact factor
Impact factor: 25.476
RIV identification code
RIV/00216224:14740/21:00119667
Organization unit
Central European Institute of Technology
UT WoS
000739837800009
Keywords in English
Low-burden TP53 mutations; CLL; clinical impact; clonal evolution
Tags
International impact, Reviewed
Změněno: 15/10/2024 14:25, Ing. Martina Blahová
Abstract
V originále
Patientswith chronic lymphocytic leukemia (CLL) bearing TP53 mutations experience chemorefractory disease and are therefore candidates for targeted therapy. However, the significance of low-burden TP53 mutations with <10% variant allele frequency (VAF) remains a matter for debate. Herein, we describe clonal evolution scenarios of low-burden TP53 mutations, the clinical impact of which we analyzed in a "real-world" CLL cohort. TP53 status was assessed by targeted next-generation sequencing (NGS) in 511 patients entering first-line treatment with chemo- and/or immunotherapy and 159 patients in relapse before treatment with targeted agents. Within the pretherapy cohort, 16% of patients carried low-burden TP53 mutations (0.1% to 10% VAF). Although their presence did not significantly shorten event-free survival after first-line therapy, it affected overall survival (OS). In a subgroup with TP53 mutations of 1% to 10% VAF, the impact on OS was observed only in patients with unmutated IGHV who had not received targeted therapy, as patients benefited from switching to targeted agents, regardless of initial TP53 mutational status. Analysis of the clonal evolution of low-burden TP53 mutations showed that the highest expansion rates were associated with fludarabine, cyclophosphamide, and rituximab regimen in both first- and second-line treatments (median VAF increase, 14.8x and 11.8x, respectively) in contrast to treatment with less intense treatment regimens (1.6x) and no treatment (0.8x). In the relapse cohort, 33% of patients carried low-burden TP53 mutations, which did not expand significantly upon targeted treatment (median VAF change, 1x). Sporadic cases of TP53 mutations' clonal shifts were connected with the development of resistance-associated mutations. Altogether, our data support the incorporation of low-burden TP53 variants in clinical decision making.
Links
| EF16_026/0008448, research and development project |
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| GA19-11299S, research and development project |
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| GA19-15737S, research and development project |
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| MUNI/A/1595/2020, interní kód MU |
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| NV19-03-00091, research and development project |
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| 90132, large research infrastructures |
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