Low-burden TP53 mutations in CLL: clinical impact and clonal evolution within the context of different treatment options

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216224:14740/21:00119667

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Low-burden TP53 mutations in CLL: clinical impact and clonal evolution within the context of different treatment options

Popis výsledku v původním jazyce

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 &lt;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 &quot;real-world&quot; 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&apos; 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.

Název v anglickém jazyce

Low-burden TP53 mutations in CLL: clinical impact and clonal evolution within the context of different treatment options

Popis výsledku anglicky

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 &lt;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 &quot;real-world&quot; 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&apos; 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Blood

ISSN

0006-4971

e-ISSN

—

Svazek periodika

138

Číslo periodika v rámci svazku

25

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

16

Strana od-do

2670-2685

Kód UT WoS článku

000739837800009

EID výsledku v databázi Scopus

2-s2.0-85113349738