Towards personalised management of CLL? Ibrutinib study reveals new way to gauge patients’ response to treatment

[bennevisplace]

Excerpts from genengnews.com/topics/omics...

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Ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has remarkable efficacy in most patients with CLL. It is becoming the standard of care for most patients requiring treatment due to its clinical efficacy and mostly tolerable side effects. However, it does not cure the disease, and patients must undergo prolonged periods of treatment.

According to Bock’s team at CeMM, CLL cells and other immune cells that respond to Ibrutinib manifest distinctive epigenetic and transcriptional patterns. These patterns predict how swiftly the treatment is having an effect on the CLL cells and how long it takes for the disease to respond in each individual patient.

In previous studies, scientists had investigated only specific aspects of the molecular response to ibrutinib, focusing largely on genetic drug resistance or the transcriptome response of cancer cells. In the current study, CeMM researchers tried a new, more comprehensive approach. They conducted a genome-scale, time-resolved analysis of the regulatory response to this drug in primary patient samples.

The scientists simultaneously monitored the activity, regulation, and expression of the CLL cells and other cell types of the immune system. Importantly, they performed this analysis at eight predefined time points during the ibrutinib therapy, following seven individual patients over a standardized 240-day period after the start of the treatment.

After the CeMM team amassed a dataset, they put it through integrative bioinformatic analysis to generate one of the first high-resolution, multi-omics time series of the molecular response to targeted therapy in cancer patients. This work, the CeMM team asserts, establishes a broadly applicable approach for analyzing drug-induced regulatory programs, identifying molecular response markers for targeted therapy.

These results will help develop personalized strategies for managing CLL as a chronic disease, which is particularly relevant for CLL as a disease of the elderly. Also, they will help stratify patients into fast and slow responders based on characteristic molecular markers and open new directions for the development of ibrutinib-based combination therapies for CLL.

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The CeMM study is published in Nature nature.com/articles/s41467-...

[bennevisplace]

If you're like me you'll be thinking " most of this is over my head". But it's the way science goes these days - collect more data and do more sophisticated analysis, enabled by massive computing power, to generate answers (sometimes answers to questions you hadn't even thought of).

The Vienna team's forensic "single cell multi-omics" approach does seem to elucidate what happens over time, when you pitch a drug against a CLL cell: events at the molecular level follow the same course but at a speed particular to the individual patient.

In this talk youtube.com/watch?v=ZwaX_u-...(Not working as expected?) (13:30-20:00 mins and 37:00 mins) we get a glimpse of the potential in this technique to improve treatment decisions, i.e. which combination of targeted drugs would a particular patient likely respond to best.

[BeckyLUSA]

Thanks for posting. An interesting read (actually, I only skimmed it) but unfortunately a little above my pay grade. It does appear to say though, that our CLL response to Ibrutinib is very much an individual thing...like most everything about CLL!

[bennevisplace in reply to BeckyLUSA]

Yes, and not just to Ibrutinib. I guess the hope is that this technique ultimately will be able to explain why patients with the same CLL genetics respond differently to the same drug. And better inform treatment choices.

[BeckyLUSA in reply to bennevisplace]

Yes!

[Smakwater]

Fascinating bennevisplace,

Articles like this and the video post always remind me of the people I have met who say things like "I'm bored".

The more information that I consume, the smaller I feel.

But, never bored.

JM

[bennevisplace]

I agree with you Smakwater. Cutting edge stuff like this is a workout for the old grey matter. The unfamiliarity is challenging but at the same time stimulating.