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

Introduction Patients withTP53dysfunction, assessed by del(17p) orTP53mutations, 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 ofTP53dysfunction. Area covered A literature search was undertaken on clinical trials and real-world experience data on patients withTP53dysfunction treated with different protocols. Moreover, data on theTP53biological function and on the tests currently employed for its assessment were reviewed. Expert opinion AlthoughTP53dysfunction has less negative influence on the new biological therapies, patients with these alterations, particularly those with biallelic inactivation ofTP53, have a worst outcome with these therapies than those without alterations. At present, a determination ofTP53, 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 theTP53status, including functional assays, may become part of the current armamentarium for a better patient stratification and treatment with newer protocols.