TY - JOUR
T1 - TP53 dysfunction in chronic lymphocytic leukemia
T2 - clinical relevance in the era of B-cell receptors and BCL-2 inhibitors
AU - Morabito, Fortunato
AU - Gentile, Massimo
AU - Monti, Paola
AU - Recchia, Anna Grazia
AU - Menichini, Paola
AU - Skafi, Mamdouh
AU - Atrash, Moien
AU - De Luca, Giuseppa
AU - Bossio, Sabrina
AU - Al-Janazreh, Hamdi
AU - Galimberti, Sara
AU - Salah, Zaidoun
AU - Morabito, Lucio
AU - Mujahed, Alham
AU - Hindiyeh, Musa
AU - Dono, Mariella
AU - Fais, Franco
AU - Cutrona, Giovanna
AU - Neri, Antonino
AU - Tripepi, Giovanni
AU - Fronza, Gilberto
AU - Ferrarini, Manlio
PY - 2020
Y1 - 2020
N2 - Introduction: Patients with TP53 dysfunction, assessed by del(17p) or TP53 mutations, respond poorly to chemo-immunotherapy and fare better with the new therapies (BCR and BCL-2 inhibitors); however, it is unclear whether their response is similar to that of patients without anomalies or whether there is currently an adequate determination of TP53 dysfunction. Area covered: A literature search was undertaken on clinical trials and real-world experience data on patients with TP53 dysfunction treated with different protocols. Moreover, data on the TP53 biological function and on the tests currently employed for its assessment were reviewed. Expert opinion: Although TP53 dysfunction has less negative influence on the new biological therapies, patients with these alterations, particularly those with biallelic inactivation of TP53, have a worst outcome with these therapies than those without alterations. At present, a determination of TP53, particularly with next generation sequencing (NGS) methodologies, may be sufficient for the identifications of the patients unsuitable for chemo-immunotherapy, although integration with del(17p) would be advisable. For the future, more extensive determinations of the TP53 status, including functional assays, may become part of the current armamentarium for a better patient stratification and treatment with newer protocols.
AB - Introduction: Patients with TP53 dysfunction, assessed by del(17p) or TP53 mutations, respond poorly to chemo-immunotherapy and fare better with the new therapies (BCR and BCL-2 inhibitors); however, it is unclear whether their response is similar to that of patients without anomalies or whether there is currently an adequate determination of TP53 dysfunction. Area covered: A literature search was undertaken on clinical trials and real-world experience data on patients with TP53 dysfunction treated with different protocols. Moreover, data on the TP53 biological function and on the tests currently employed for its assessment were reviewed. Expert opinion: Although TP53 dysfunction has less negative influence on the new biological therapies, patients with these alterations, particularly those with biallelic inactivation of TP53, have a worst outcome with these therapies than those without alterations. At present, a determination of TP53, particularly with next generation sequencing (NGS) methodologies, may be sufficient for the identifications of the patients unsuitable for chemo-immunotherapy, although integration with del(17p) would be advisable. For the future, more extensive determinations of the TP53 status, including functional assays, may become part of the current armamentarium for a better patient stratification and treatment with newer protocols.
KW - BCL2 inhibitor
KW - BCR inhibitors
KW - chronic Lymphocytic Leukemia
KW - clinical outcome
KW - del(17p)
KW - ibrutinib
KW - idelalisib
KW - TP53 mutations
KW - venetoclax
U2 - 10.1080/13543784.2020.1783239
DO - 10.1080/13543784.2020.1783239
M3 - Article
VL - 29
SP - 869
EP - 880
JO - Expert Opin. Invest. Drugs
JF - Expert Opin. Invest. Drugs
SN - 1354-3784
IS - 8
ER -