The future of CLL treatment - time limited combination treatments?

Dr Nitin Jain, University of Texas MD Anderson

What is your goal for treatment? Getting rid of as much CLL as possible and having a long remission? Or containing the CLL and putting it into reverse for a long time?

This excellent talk from Dr Jain outlines the current clinical data which is perhaps slowly moving specialist opinion away from both FCR chemotherapy and long term Ibrutinib / acalabrutinib treatment towards Venetoclax combination treatments. Dr Jain particularly seems to advocate this more strongly for the younger patient. The rate of change is certainly increasing in CLL treatment as this slide of the history shows.

The clinical data is carefully explained and lined up to support the view that some form of Venetoclax containing combination is likely to become the gold standard treatment for CLL. It does move quickly so you may feel the need to hit pause and rewind a few times, especially if you have not heard of some of the trials before.

Here in the UK we cannot always get Venetoclax firstline depending on our markers. But in combination with rituximab it is a fully-funded second line treatment for anyone whatever their markers. This talk argues that this is an option worthy of serious consideration, and that it may be preferential to using long term Ibrutinib or acalabrutinib early in the disease.

Ultimately we are talking about two treatment strategies here.

Intermittent treatment with time-limited therapies with a goal of getting as close as possible to eradicating the disease.
- FCR
- Venetoclax containing combinations
Continuous treatment with a BTK inhibitor to slow the rate of growth of the disease and put it into reverse.
- Ibrutinib
- Acalabrutinib

There are a number of clinical trials that will make it clearer which of these strategies is the best in the really long term. And not all experts will completely agree with Dr Jain’s conclusions. This talk is well worth a listen to help understand the thinking behind this debate.

It is worth pointing out as Dr Jain does that some people are still effectively cured by FCR, and so it is definitely still possible to support that as an option, especially for the young fit patient with good markers. And Ibrutinib or acalabrutinib are also very good medicines at holding someome’s CLL at bay. So whether you choose them early in the disease or reserve them for those patients who do not manage to get to undetectable disease status with a combination treatment is definitely debatable.

What if I am currently on Ibrutinib or Acalabrutinib?

This talk does not take away from the excellent efficacy and safety data of these two medicines. And most experts will probably still advise patients that currently if they are doing well on either of these two medicines they should simply keep taking them.

The clinical data is still being collected in large studies. And so far as far as I am aware there is no published data about adding Venetoclax to patients on long term treatment with a BTK inhibitor. It does seem likely that will turn out to be a great strategy, however. So for now, one could simply think of yourself as in a holding pattern with long term treatment whilst other data is gathered. Yes, perhaps at some point in the future it might be possible to add Venetoclax or switch with the goal of getting to undetectable status and being able to stop all medicines.

But clearly this is something to discuss with your CLL specialist and even in this talk which was strongly advocating for the data for venetoclax, Dr Jain did not advise that people should stop their current treatment and immediately switch. It is always important to remember that there are pros and cons to all courses of action. And your own case is specific so do not assume that what you hear in a particular talk is the best thing for you as an individual. Weighing up risks and benefits of different options for you is exactly the role of a CLL specialist, and with the way data is emerging so rapidly at the moment this stresses the importance of seeing someone who is a real expert and can guide you.

Conclusion

What is encouraging for all of us is whatever order we take these medicines in there are a number of really good treatments for our CLL now available that only a few years ago simply didn’t exist. Most of us will probably use more than one of these options through the course of our lives.

Other treatments are also being developed, which does mean that we can hope for good disease control for many patients. This makes managing our immune complications such as fatigue, infection and inflammation even more important.