They write in a Journal of Clinical Oncology article published today that anyone diagnosed with progressive chronic lymphocytic leukemia (CLL) should be tested for the presence of the TP53 gene mutation before starting any treatment.
“Patients with the TP53 mutation are unfortunately less likely to respond to existing drugs and their five-year survival is much lower,” lead author David Gonzalez de Castro from the ICR and The Royal Marsden says. “Instead of receiving drugs that are unlikely to help them, patients with this mutation should be first in line for clinical trials of experimental treatments.”
CLL is a variable disease that can be aggressive in some patients while others never experience symptoms or require treatment. Scientists have therefore been looking for tests to determine a patient’s likely prognosis and guide the treatment they receive. CLL is usually treated with chemotherapy and more recently this has been combined with immunotherapy. A number of new drugs for CLL are at clinical trial stage, while other experimental treatments include transplants of bone marrow, stem cells or cord blood.
When functioning properly, TP53 is a “tumour suppressor gene” that helps prevent cancers developing by regulating DNA repair and cell division. When TP53 is mutated, the process of programmed cell death fails and cells are able to multiply out of control.
The ICR scientists scanned the DNA of cancer samples from 529 CLL patients who had taken part in an earlier chemotherapy drug trial* to determine whether they had a TP53 mutation. They correlated this genetic information with trial data about the patients’ response to treatment and the length of time they survived.
They found TP53 mutations in 40 patients (7.6 per cent), and identified a significant association between carrying the mutation and both failure to respond to treatment and poor survival. Around 83 per cent of patients without the mutation responded to existing drugs, while just 27 per cent of patients with the mutation responded. One in five patients with the mutation was alive after five years, compared to three in five patients who did not carry the mutation.
Senior author Professor Gareth Morgan from the ICR and The Royal Marsden says: “Testing for the TP53 mutation is the most accurate measure we have developed so far of predicting patients’ likely response to treatment. Identifying patients who are unlikely to benefit from standard treatment allows us to give these patients a better chance of survival by helping them join clinical trials for new therapies.”
Media Contact: ICR Science Communications Manager Jane Bunce on 0207 153 5106 or after hours 077217 47900
Notes to editors:
CLL is characterised by an increased number of white blood cells called lymphocytes. About 2,750 people are diagnosed with CLL each year in the UK, most in late middle age onwards.
* The patients took part in the LRF Chronic Lymphocytic Leukemia 4 trial, comparing the established chemotherapy drug chlorambucil with new drug fludarabine (taken either alone or in combination with prodrug cyclophosphamide). The trial started in 1999 and data analysis continues.
The study was a collaboration between scientists at the ICR, The Royal Marsden Hospital, the Clinical Trial Service Unit at Oxford University and Royal Bournemouth Hospital. It was funded by The Royal Marsden, the ICR, the National Institute of Health Research Biomedical Research Centre and the Chronic Lymphocytic Leukemia Global Research Foundation. The original trial was funded by Leukaemia & Lymphoma Research (previously known as the Leukaemia Research Fund).
The Institute of Cancer Research (ICR)
- The ICR is Europe’s leading cancer research centre
- The ICR has been ranked the UK’s top academic research centre, based on the results of the Higher Education Funding Council’s Research Assessment Exercise
- The ICR works closely with partner The Royal Marsden NHS Foundation Trust to ensure patients immediately benefit from new research. Together the two organisations form the largest comprehensive cancer centre in Europe
- The ICR has charitable status and relies on voluntary income, spending 90 pence in every pound of total income directly on research
- As a college of the University of London, the ICR also provides postgraduate higher education of international distinction
- Over its 100-year history, the ICR’s achievements include identifying the potential link between smoking and lung cancer which was subsequently confirmed, discovering that DNA damage is the basic cause of cancer and isolating more cancer-related genes than any other organisation in the world
For more information visit www.icr.ac.uk
The Royal Marsden Hospital
The Royal Marsden opened its doors in 1851 as the world’s first hospital dedicated to cancer diagnosis, treatment, research and education. Today, together with its academic partner, The Institute of Cancer Research (ICR), it is the largest and most comprehensive cancer centre in Europe treating over 44,000 patients every year. It is a centre of excellence with an international reputation for groundbreaking research and pioneering the very latest in cancer treatments and technologies. The Royal Marsden also provides community services in the London boroughs of Sutton and Merton and in June 2010, along with the ICR, the Trust launched a new academic partnership with Mount Vernon Cancer Centre in Middlesex. Since 2004, the hospital’s charity, The Royal Marsden Cancer Charity, has helped raise over £50 million to build theatres, diagnostic centres, and drug development units.
Prince William became President of The Royal Marsden in 2007, following a long royal connection with the hospital.