Clinical Outcomes in Patients with Multi-Hit TP53 Chronic Lymphocytic Leukemia Treated with Ibrutinib.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Christian BrieghelCarsten U Niemann

Abstract

TP53 aberration (TP53 mutation and/or 17p deletion) is the most important predictive marker in chronic lymphocytic leukemia (CLL). Although each TP53 aberration is considered an equal prognosticator, the prognostic value of carrying isolated (single-hit) or multiple (multi-hit) TP53 aberrations remains unclear, particularly in the context of targeted agents. We performed deep sequencing of TP53 using baseline samples collected from 51 TP53 aberrant patients treated with ibrutinib in a phase II study (NCT01500733). We identified TP53 mutations in 43 patients (84%) and del(17p) in 47 (92%); 9 and 42 patients carried single-hit and multi-hit TP53, respectively. The multi-hit TP53 subgroup was enriched with younger patients who had prior treatments and unmutated immunoglobulin heavy-chain variable region gene status. We observed significantly shorter overall survival, progression-free survival (PFS), and time-to-progression (TTP) in patients with multi-hit TP53 compared with those with single-hit TP53. Clinical outcomes were similar in patient subgroups stratified by 2 or >2 TP53 aberrations. In multivariable analyses, multi-hit TP53 CLL was independently associated with inferior PFS and TTP. In sensitivity analyses, excluding muta...Continue Reading

References

Apr 1, 1971·Proceedings of the National Academy of Sciences of the United States of America·A G Knudson
Jan 3, 2001·The New England Journal of Medicine·H DöhnerP Lichter
Feb 4, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Davide RossiGianluca Gaidano
Aug 11, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Thorsten ZenzStephan Stilgenbauer
Aug 13, 2011·The New England Journal of Medicine·David L PorterCarl H June
Mar 8, 2012·Blood·Thorsten ZenzStephan Stilgenbauer
Apr 18, 2014·Nature Reviews. Cancer·Kathryn T BiegingLaura D Attardi
May 30, 2014·The New England Journal of Medicine·Jennifer A WoyachJohn C Byrd
Aug 10, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lijian YuJennifer R Brown
Nov 9, 2016·Clinical Epidemiology·Caspar da Cunha-BangCarsten Utoft Niemann
Jul 18, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Cameron J TurtleDavid G Maloney
Feb 23, 2018·Leukemia·J MalcikovaUNKNOWN European Research Initiative on Chronic Lymphocytic Leukemia (ERIC) — TP53 network
May 30, 2019·The New England Journal of Medicine·Nitin JainWilliam Wierda
Jul 12, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Peter HillmenTalha Munir
Sep 12, 2019·Cell Reports·Lawrence A DonehowerDavid A Wheeler
Jul 30, 2020·The New England Journal of Medicine·Jan A Burger
Jul 30, 2020·The New England Journal of Medicine·Inhye E AhnAdrian Wiestner
Aug 1, 2020·European Journal of Haematology·Kathrine AarupCarsten Utoft Niemann
Aug 17, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Kerry A RogersJohn C Byrd
Oct 8, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Inhye E AhnAdrian Wiestner
Oct 23, 2020·Annals of Oncology : Official Journal of the European Society for Medical Oncology·B EichhorstUNKNOWN ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org

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Citations

Jun 16, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Riccardo BombenValter Gattei

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