Low-burden TP53 mutations in CLL: clinical impact and clonal evolution within the context of different treatment options
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F21%3A00074912" target="_blank" >RIV/65269705:_____/21:00074912 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14740/21:00119667
Result on the web
<a href="https://ashpublications.org/blood/article/138/25/2670/475902/Low-burden-TP53-mutations-in-CLL-clinical-impact" target="_blank" >https://ashpublications.org/blood/article/138/25/2670/475902/Low-burden-TP53-mutations-in-CLL-clinical-impact</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1182/blood.2020009530" target="_blank" >10.1182/blood.2020009530</a>
Alternative languages
Result language
angličtina
Original language name
Low-burden TP53 mutations in CLL: clinical impact and clonal evolution within the context of different treatment options
Original language description
Patients with 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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30205 - Hematology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Blood
ISSN
0006-4971
e-ISSN
—
Volume of the periodical
138
Issue of the periodical within the volume
25
Country of publishing house
US - UNITED STATES
Number of pages
16
Pages from-to
2670-2685
UT code for WoS article
000739837800009
EID of the result in the Scopus database
2-s2.0-85113349738