Prognostic and Therapeutic Significance of TP53 Alterations in CLL

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There are several novel agents, such as ibrutinib, idelalisib, and venetoclax, that could improve outcomes in CLL patients with 17p deletions and TP53 mutations.
There are several novel agents, such as ibrutinib, idelalisib, and venetoclax, that could improve outcomes in CLL patients with 17p deletions and TP53 mutations.

In chronic lymphocytic leukemia (CLL), significant progress has been made to understand the disease and elucidate optimal treatment strategies, particularly for patients with chromosome 17p deletions and TP53 mutations. A recent review article published in the Annals of Hematology described the prognostic role of 17p deletions and TP53 mutations in CLL and the currently available treatment options for patients.1

In CLL, patients with 17p deletions and TP53 mutations have lower response rates and more aggressive disease compared to patients without these abnormalities. These abnormalities were recently incorporated into a prognostic model called the International Prognostic Index for Chronic Lymphocytic Leukemia. The model labels patients with 17p deletions and/or TP53 mutations as high risk.

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The study authors described several novel agents, such as ibrutinib, idelalisib, and venetoclax, as treatments that could improve outcomes in CLL patients with 17p deletions and TP53 mutations. The study authors also explored the role of allogeneic transplantation as a therapeutic approach, writing that despite novel agents, “long-lasting remissions are not expected, especially in patients with relapsed disease.” They concluded that allogeneic transplantation should still be offered to fit CLL patients with TP53 alterations.

“It is hoped that further progress in targeted therapy and the judicious use of historically important interventions, such as chemotherapy, monoclonal antibodies, and reduced-intensity allogeneic transplantation, will provide patients with CLL in general, and those with TP53 abnormalities in particular, with a better prognosis and brighter outlook than in the recent past,” the study authors wrote.

Disclosures: The review article was funded by AbbVie. AbbVie also participated in the interpretation of data, review, and approval of the content.

Reference

  1. Buccheri V, Barreto WG, Fogliatto LM, Capra M, Marchiani M, Rocha V. Prognostic and therapeutic stratification in CLL: Focus on 17p deletion and p53 mutation. Ann Hematol. 2018;97:2269-2278. doi: 10.1007/s00277-018-3503-6

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