Today NICE announced that they have agreed to fund Venetocolax plus obinutuzamab for all first line patients with CLL who want to take it in England. This means that nobody will be forced to face the choice of agreeing to take FCR chemotherapy or receive no treatment.

Does this mean the end of FCR which has been the gold standard for first line treatment of CLL for a number of years? It is now more than 20 years since the first groups of patients were given the combination of fludarabine, cyclophosphamide and Rituximab. A significant number of those patients still haven’t needed any further treatment and some doctors say we should refer to them as cured from their CLL. It didnt work for everyone. There are some genetic markers that indicate it is unlikely to work at all, some that suggest it is less likely to work.

Venetoclax and Obinituzimab is presented as the natural replacement for FCR. Like FCR it is time limited. Obinituzimab is the more potent more selective follow up to Rituximab and so works hand in glove with venetoclax to deliver deep remissions, and in many cases MRD undetectable status which means that less than 1 in 10,000 cells tested are CLL cells. And so the hope and expectation is that a good proportion (maybe even a higher rate) will also have the really long remissions that make you wonder just how long someone must remain well before you say they are cured.

No doubt some will relapse, the current hope is that re-treatment with a Venetoclax combination will still be possible. And some will not have an adequate response, which means that they will qualify for ibrutinb under current NICE rules.

Side effect wise this combination is not without its risks but for most patients it will be better tolerated than FCR. There will need to be a careful risk-benefit conversation on an individual basis with doctors as to which patients will remain suitable for FCR and which will be better suited by being offered Venetoclax plus obinutuzimab but I rather suspect that given the emotional connotations of being treated with chemotherapy vs being treated with specific targeted treatments many will opt to choose the newer combination.

Of course at this point we simply do not know what is the optimum long term treatment order or indeed if it really matters which medicine you choose first. Trials like FLAIR have not yet read out and so we do not know whether starting with FCR then when any further treatment is needed reaching for one of the selective agents is going to be a better strategy in the long term than starting off from the beginning with the selective treatments. Given that this medicine is now available and funded in England, it may be that FCR use will drop off quite dramatically before this long term clinical data is available.

It is always easy to get caught up in the excitement about new medicines. So the availability of this choice now makes it even more important to discuss your treatment with a real expert in CLL before finalising which option you want to go for. The top experts will have been involved in clinical trials with Venetoclax already and so will be more confident in understanding its characteristics and which side effects are more troublesome and which patient groups may still do better with the old gold standard FCR.

Yesterday we also heard that acalabrunib has been licensed across Europe which for the moment still includes the UK. Funding is still being considered for this at the moment at NICE so we await to see with interest what their decision will be. In the meantime there is a safety study opening which will be enrolling UK patients.

Its worth adding that per NICE, both Ibrutinib monotherapy and Venetoclax plus rituximab is already funded for all second line patients. So whether you have been treated or not, you are now able to ask for a Venetocolax combination as your next treatment if you live in England and that is what you would like to take.

So today may mark the beginning of the end for FCR a treatment which when it was released revolutionised the life expectancy of patients with CLL. It is remarkable that yesterdays remarkable breakthrough may well be superseded by the new selective treatments. We live in exciting times for the treatment of blood cancers with advances coming rapidly in many different conditions.