If push came to shove would you really choose HSCT as a first-line treatment to treat your MS?
When asked on the blog yesterday which DMT would I choose if I had MS, I chose HSCT. One of my patients, who I have been looking after for over a decade, sent me an email stating how upset she was that I had never offered her HSCT. I clearly need to explain my position so as not to upset anyone else.
Firstly, HSCT is not on offer as a routine NHS therapy. At the moment HSCT is only considered as a 2nd or 3rd-line treatment in the most active patients. Another problem is that it is not on offer across the country. There are only a handful of MS centres that are prepared to refer their patients for HSCT. This means that access to HSCT is not equitable and explains why an increasing number of patients are having to travel abroad, at great personal cost, to receive this therapy. Inequity of care is against one of the founding principles of the NHS and is unacceptable.
The block in access to HSCT seems to be at the level of the neurologist/MSologist. NHS England guidelines for bone marrow transplant (BMT) units allows them to use up to 15% of their procedures to treat autoimmune conditions, which includes multiple sclerosis. As BMT units exist across the country access to these units would simply require a referral from a neurologist to the unit to perform HSCT on patients with MS. However, the latter is unlikely to happen unless the local MSologist champions HSCT as a procedure and gets their local haematology unit on board. It always takes a local champion to make things happen and our Barts-MS champion is Dr Ben Turner.
Another factor that has changed in the last 10 years is the strength of the evidence-base showing how effective HSCT really is as a treatment for MS. The most recent MIST trial, the first large randomised controlled trial, and several meta-analyses of HSCT, which have been extensively discussed on this blog, have confirmed that HSCT is a very effective therapy. At the same time the risks associated with HSCT have improved and the mortality in most BMT units is now below 1% for MS. This is now tipping the scales in favour of HSCT becoming a mainstream treatment for MS. There is however resistance from the MS community about HSCT been offered as a first-line therapy. Why? I suspect because the risk:benefit profile of HSCT has yet to be compared in a head-2-head study against our most effective licensed treatment. This why we are planning to do a head-2-head study of alemtuzumab vs. HSCT in the hope of generating this evidence. We know already that HSCT will be more cost-effective than alemtuzumab, but will it be more effective and as safe? Don’t try and second guess the results of this trial; I would not be surprised if there is no difference between these two treatments in terms of efficacy.
Please remember that most of the proponents of HSCT as a treatment for MS recognise that the major benefits from treatment will only be derived if HSCT is used early in the course of the disease. This explains why most BMT units don’t offer HSCT to pwMS with more advanced, or progressive, MS. However, this does not stop private, fee-for-service, units offering HSCT to all-comers. If you have the money and are willing to travel abroad you will be able to find a BMT unit that will treat you. I think this is wrong and will not happen in the NHS when HSCT eventually becomes widely available. We have to be honest with our patients about the risks and the benefits and why we will limit HSCT to those who benefit the most. In fact there is evidence that more advanced patients may actually be made worse by HSCT; the chemotherapy used to ablate the immune system is neurotoxic and may speed up neuronal loss. In addition, infections are common when you have HSCT and infections are well known to worsen MS disability in more advanced disease.
Please be aware that HSCT is not for the faint-hearted. It is a risky therapy with serious adverse events and quite a high mortality. Even a mortality rate of 0.3-0.5% is high when compared to other licensed DMTs. Should this stop us from offering HSCT first-line? I think not. If we are prepared to offer alemtuzumab, with its risk profile as a first-line treatment, why not HSCT? Most pwMS would agree that the decision regarding what is an acceptable risk to take should be taken by the patient and their families, and not the neurologist or other HCP. There is data showing that neurologists are much more risk-averse than pwMS. Neurologists need to acknowledge this bias, which is likely to be an unconscious bias, and let their patients make the decision.
What I am really trying to do by stating that if I had MS I would choose HSCT as my treatment is to reframe the DMT debate, particularly in relation to access to highly effective DMTs. By focusing on HSCT as a first-line treatment it should at least consider what your treatment objectives are in MS.
Framing is another a cognitive bias that was identified by Daniel Kahneman, the Nobel laureate, and his partner Amos Tversky. By moving the frame to the right, i.e to include HSCT as a 1st-line therapy, it makes it more likely for pwMS and their neurologists to choose more effective treatments. We now know that people who start on a low to moderate efficacy DMT do worse on average than those who start on a high or very high efficacy therapies do better. Despite this the majority of pwMS are not told this and are started on a low efficacy or platform DMTs without ever being given the option of a high efficacy DMT. Why? It is not due to lack of access to treatments as we now have several NICE and NHS England approved high efficacy DMTs available as first-line treatments.
So yes, if I had active MS I would want to have the full spectrum of high-efficacy DMTs available to choose from including HSCT. I would want to know about their relative efficacy and what the aim of the treatments are. I would certainly want to have a discussion about the possibility of a potential cure. Wouldn’t you?
By framing the spectrum of efficacy by having HSCT within the frame may nudge patients and their neurologists to move up the treatment ladder and choose a high efficacy DMT.
Unfortunately, HSCT as a first-line option is not going to happen any time soon, which is why I am trying to nudge the community to start debating the issue in earnest and why I want us to have a citizens jury on the issue.