TP53 dysfunction in chronic lymphocytic leukemia: clinical relevance in the era of B-cell receptors and BCL-2 inhibitors

Fortunato Morabito, Massimo Gentile, Paola Monti, Anna Grazia Recchia, Paola Menichini, Mamdouh Skafi, Moien Atrash, Giuseppa De Luca, Sabrina Bossio, Hamdi Al-Janazreh, Sara Galimberti, Zaidoun Salah, Lucio Morabito, Alham Mujahed, Musa Hindiyeh, Mariella Dono, Franco Fais, Giovanna Cutrona, Antonino Neri, Giovanni TripepiGilberto Fronza, Manlio Ferrarini

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)869-880
Number of pages12
JournalExpert Opin. Invest. Drugs
Volume29
Issue number8
DOIs
Publication statusPublished - 2020

Keywords

  • BCL2 inhibitor
  • BCR inhibitors
  • chronic Lymphocytic Leukemia
  • clinical outcome
  • del(17p)
  • ibrutinib
  • idelalisib
  • TP53 mutations
  • venetoclax

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