Blood cancers

Aussie perspective puts focus on gene P53 in new CLL guidelines

International guidelines for the management of CLL have been updated for the first time since 2008 – and for the first time have included an Australian representative amongst the authors.

Professor John Seymour told the limbic collaboration with the CLL working group ‘reflects the increasing engagement and increasing profile of Australian haematology in the field’.

The updated guidelines also reflect new discoveries in the clinical relevance of mutations, current use of clinical staging and biomarkers, and the increasing role of assessing minimal residual disease (MRD).

Professor Seymour, from the Peter McCallum Cancer Centre, Royal Melbourne Hospital and the University of Melbourne, said understanding around the mutational profile and the spectrum of mutational changes within CLL has grown enormously.

“So the emphasis here is particularly on a mutation in the gene P53. It has been long recognised that a more easily detectable abnormality – deletion of chromosome 17p – has been an important determinant of treatment choice for a number of years but a new change in these guidelines is the recognition that a P53 mutation has an equivalent impact upon appropriate treatment selection.”

However P53 mutation testing is relatively infrequently performed in Australia, Professor Seymour said.

“Funding is one of the issues – it’s not currently reimbursed – but also the availability of a reliable, validated test had previously been difficult but is now more widely available with the utilisation of next generation sequencing modalities.”

Professor Seymour said while the capacity to robustly measure minimal residual disease (MRD) via multichannel flow cytometry has been widely available for more than a decade, there has been more recent recognition that long-term outcomes for patients are profoundly improved if the treatment delivered is able to attain a high quality remission.

“So use of MRD negativity as a therapeutic end point has been the more recent change.”

The guidelines also include advice regarding the baseline assessment and prophylaxis of viral diseases in patients before and during CLL treatment.

“This is recognition of the risk from many of the therapies used to treat CLL including reactivation of latent viral infections, particularly hepatitis B and CMV, that are quite easy to treat preemptively but can be life threatening if left to become an uncontrolled infection.”

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