New hope through advances in blood cancers ~ Targeted drugs bring swift relief on a Clinical Trial.

This is a long-read article. I included a lot of detail because I was desperate to pick up all the tips and find all the encouragement I could when I was trying to digest what was happening myself - when massive decisions had to be made. It focuses on my personal experiences of diagnosis, disorientation & treatment as I thought that would resonate with much that others go through too. The links can be accessed as a stand-alone resource, though. I recommend the video clips and short films to anyone on this path who is keen to understand more. Many of them are less than five minutes long. 

On 18th October 2018, I enrolled on the UK FLAIR trial.  At that point, the clinical trial had been running for just over four years. I’d been diagnosed with CLL blood cancer and placed on ‘Watch and Wait’ three years previously in December 2015.

As recruitment for the trial recently ended (on 31^st March 2021), I decided to mark the occasion by recording my experiences of diagnosis and participation in the clinical trial - and the reflections they prompted - hoping this might help others, just as reading articles by people diagnosed with CLL before me helped me more than most of the technical material on offer.

I want to start my story at the beginning,  for - as with many of us - things began as a completely unexpected side story, when we were going around, perhaps feeling perfectly well, with no clue that something was amiss..

For me diagnosis had come about as the incidental result of a breast screening recall. The scan had detected swelling of my lymph nodes in the armpit area and, as it couldn’t be put down to any recent infection I might have still been fighting, I was given a core biopsy on the spot.

The results came in three anxious weeks later.

I was, at first, told they'd found non-Hodgkin's Lymphoma cells. This couldn’t have been more unhelpful, particularly as my dad had died of Non Hodgkin's Lymphoma at the age of 57. At the time of the breast screening recall, almost 20 years later, I was turning 56 myself a few days later on the 27^th December. My husband and I were burdened with the devastating-sounding information on Christmas Eve in 2015 by a breast consultant who wasn't able to give us any further information. We'd have to wait until early January to discover anything further from the Haematology/Oncology department I was now being referred to.

The breast consultant, who came across as a gentle soul, had nevertheless delivered the sketchy information in the matter-of-fact tones of someone fairly desensitized to its content. I was one in a long list of people he must see before his Christmas break and, at any rate, I’d be on the caseload of a separate department. He was merely passing on a message.

However, he didn’t pass on even what he knew fully, and we – in a state of shock – couldn’t think what we needed to ask. On receipt, an interminable-feeling fortnight later, of a copy of his letter to my GP we learned that the cells were low grade – rather a significant fact to have omitted, surely? This positive news was tempered by the language he used, though, as he spoke of me ‘sadly’ having returned this result. It’s definitely, in my experience, not always helpful receiving copies of letters worded for and addressed to a GP.

I’m sure the doctor meant well, and was trying to fulfil his role sensitively. But as we parted on Christmas Eve he wished us a happy Christmas. A convention, of course – an established form of words uttered automatically, in an attempt to conclude an awkward and difficult meeting affably. It felt laughably inappropriate, though, and I wholeheartedly wished I’d been told nothing until I had been able to see the relevant people who would take the time, and were able and authorised, to give us a full explanation about what was going on.

For what we had been told, had understandably, struck fear into our hearts and we went away fearing the worst, not knowing what or whether to tell my mother or daughter. I remember we drove to a coffee bar - following a normal mid-morning pattern of behaviour, but feeling anything but normal. I had to shout to stop my husband pulling out from a side road into the path of another car on the way there. We wandered into an independent bookshop near the cafe, going through the motions of Christmas Shopping, where I picked up a book with a black cover edged in gold, like a funeral invitation, entitled Being Mortal by Dr Atul Gawande. I knew nothing about it, but it looked about right. I bought it for myself.

Over the festive period, my husband and I kept up a cheerful front in the daytimes, making sure nobody suspected anything was amiss. But as soon as we were alone later, and into the night, we'd be back on the computers terrifying ourselves by trying to take in a dizzying range of general information about all the apparent possibilities. We had nothing specific to go on, so were of course imbibing terrifying messages about any number of conditions - and potential levels of severity within those - posted at varying and often unspecific points in time. Once uploaded, material typically seems to remain online in perpetuity.

Without any specific information, especially, it definitely would have been better not to have bothered going on the internet and terrifying ourselves utterly by looking for answers to questions we didn’t even know how to formulate at this juncture.

We all know that for a fortnight around Christmas and New Year it's fairly impossible to talk to anyone in an official capacity or to find anything out in the normal way. This sounds melodramatic with hindsight but, as I imagine many others who have been given alarming diagnoses just before Christmas have done, I saw in the New Year that year imagining it could well be my last. My biggest concern was for those I felt I'd be leaving in the lurch. I wondered how on earth their lives would work out and felt a keen sense of loss thinking that I wouldn't be there with them to share it.

Most of us have a tendency to catastrophise at such times. We fill the gaping void that we feel opening up with nightmares straight from our own imagination. I was no exception.

 A few weeks later, when my Haematology appointment finally came round, we were told that the specific condition I had was called “SLL” - or “SLL/CLL” (Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia). These two diagnoses, I was told, are very similar; indeed, they overlap.

We also learned at this point that there are over 60 types of Non-Hodgkin’s Lymphoma, and that there was very little similarity between my father's condition upon presentation (Intermediate Grade Non-Hodgkin's) and the very early, chance discovery of excessive lymphocytes in my blood. It does seem to me that, in the light of phenomenal developments in the 25 years since he died, if he had presented with the same problems nowadays there might have been a very different outcome even for him, though. I imagine he could still have been here.

We were told that SLL morphs into CLL in the course of time. I was never quite sure of the significance of this but we were reassured, anyhow, that CLL ends up being for many people what you could call a ‘maintenance disease’. Meaning, it can be managed with various treatments over a long period of time. I was reassured that however things shaped up I was one of the younger patients with this disease, was otherwise fit and well and was likely to be in the cohort with a good chance of ‘long-term survival’, as they call it.

The terminology in itself is alarming.

Have you ever noticed that at times when you’re unwell there seems to be an objective, scientific part of your brain that takes an interest in the process you’re going through? I often have. So, when eventually given my diagnosis - although I was, naturally, extremely concerned - it distracted me somewhat to observe the manifest enthusiasm of the boffins in the Haematology department of our local hospital. For the first six months or so I was seen by an alternating pair of female registrars whose youthful enthusiasm was infectious. Scientists first and foremost, and accustomed to having had to predominantly break devastating news to their patients, they became animated and starry-eyed when discussing the head-spinning developments within their field at this point in medical history.

One of them told me, excitedly: "If you have to contract a cancer nowadays, this is the one to get!" and advised me, almost conspiratorially (as if I could do anything about it! ...)

"The longer you can hold out without needing us to intervene, the better - the more options, and better researched treatments, there will be."

I left that day buoyed up by her positivity and faith in the new treatments being ushered in, and learned soon afterwards just how centrally important current advances in blood cancer research are - how new knowledge is enabling scientists to progressively develop revolutionary treatments for other cancers and conditions of the result of this too.

Nowadays it seems as though the distinction between SLL and CLL needn't concern the patient as it's not going to make any difference to the modern treatments on offer, or to outcomes. After a while, I gave up trying to understand things too technically. I learned that CLL/SLL are blanket terms for a great many unique manifestations of a circulatory condition that is either more fluid in form (Small Lymphocytic Leukemia) or lumpy (Chronic Lymphocytic Leukemia).

I was also reminded that a lot of what is written on the internet is now out of date, and the science is moving so quickly in the arena of blood cancers that even many articles written just a couple of years ago would concern us unnecessarily. For many predicaments which were truly worrying always before have morphed into fairly manageable propositions now - such is the skill and greater understanding evolving exponentially in these times we are fortunate enough to live in.

After almost three years on ‘Watch and Wait’, things had progressed to the point where it was becoming pretty clear I needed treatment. The nodes in my neck, groin and armpits had swollen markedly. This only became really noticeable over a period of about nine months.

It happened so gradually that it didn't bother me unduly - after all, I was feeling no pain and experiencing no other symptoms, and we don't look at ourselves that much of the day, do we? We kind of get used to changes in the way we look gradually - like when we put on weight or lose it – while those close to us are confronted with the increasing deformity of our usual features constantly, and their reactions are what tend to make us aware of the visibility of whatever has changed. The most difficult thing for me at the time was that my student daughter felt hardly able to look at me, and I could feel an emotional distance had developed between us. For her, the unavoidable physical change screamed 'cancer' with every glance.

How I looked a few months before I embarked on the trial (see below how I looked before this, and how I looked again after only a month or so on the drugs) 

Initially, I’d been told that I might very well have 'ten years or more' relatively unimpeded by CLL. When this hypothetical estimate was revised twelve months or so later, as my lymphocyte count started increasing rapidly, I was told that it might in fact be only 'around three years' into the Watch and Wait period that I needed treatment. I learned later that my daughter had understood I’d initially been given ten years to live, and then that that had been cut to only three! No wonder the poor girl froze and I felt an unspoken barrier had erected itself between us around that time.

I wanted to tell my story to encourage others to understand that (thanks to the rapidly advancing knowledge in the field, with treatment safety and options evolving accordingly) the majority of people who receive this diagnosis nowadays are in a very different position, vis-a-vis conventional treatments, to the one they would have found themselves in in the past - as long, of course, as they are able to tolerate the latest treatments well. But apparently an overwhelming majority do.

In the summer of my third year from diagnosis I applied for a place on the trial. Once my lymphocyte count began to soar to well over 100, and swellings in my armpits and groin were as pronounced as the visible ones in my neck – i.e. as treatment had become imminent - a blood test to analyse something called IgHV mutation status was performed. In America this is often done close to the time of diagnosis, as it provides useful prognostic information and the insurance companies can be charged within the private healthcare system. But it is usually done later in the UK because of the cost. 

I had been tipped off at my previous appointment that we were looking for the result 'mutated' and remember feeling winded when the tests returned the result 'unmutated'. The room began to swim before my eyes, and I sat through the rest of the appointment in a stunned state, afraid of untold terrors. I went off home for the weekend with wads of literature I'd been given about the clinical trial, describing in alarming detail each of the possible treatments and all their potential side effects. After leafing through, I remember tossing the papers into a drawer and closing it in disgust. That was when I hit my lowest point. I sat reading and watching videos on YouTube the whole of that weekend, and the outlook looked bleak indeed. But I also learned a lot.

I've always been someone who wants to know, at least broadly, what I'm dealing with when something challenging has needed facing in life. One of the things I learned that weekend - in simplified terms - was that:

                      CLL can be understood as roughly a 'disease of thirds'.

This means:

·        A third of those with the disease won’t ever become ill or need any treatment. Some will never even know they have it, for that reason.

·        A further third will have ‘indolent disease’ which will need treating at some point later (many people in this category, like me, will be diagnosed in a roundabout way, as the result of attending a healthcare facility for some other reason).

·        The final third will present with symptoms needing immediate treatment – these are the individuals with more aggressive CLL.

A fairly accurate prognosis can be made from the outset if IgHV mutation status tests are done when someone is first diagnosed, as the indicator of whether the CLL will become active is already present and doesn't change throughout the course of the disease. Yet I can understand, when I think about it, why the NHS doesn't do early mutation status tests if in many cases (at least 33%) the expense wouldn't be justified by really useful information. Where the 'Watch and Wait' policy has prevailed, too, the genetic mutation results would mainly have provided results of academic interest if the decision about when to start treatment were still to be governed by the speed the lymphocytes (rogue white blood cells) were multiplying and the manifestation of what they call 'B Symptoms' (that is, swelling in the lymph nodes, debilitating tiredness and night sweats).

For me personally, however, the delay in discovering which of the groups I belonged in meant that the reassurance my family and I had felt - when we’d been initially informed that I might not need treatment for a very long time, and maybe never would - was abruptly scuppered once it became clear that something was beginning to kick off, and I was told I would indeed be likely to need treatment within the next few years. Naturally, I had passed the initial, encouraging-sounding message - “quite possibly 10 + years until treatment; maybe never” - on to my daughter and to my mum who, remember, had lost her husband to Non-Hodgkin's when they’d been the same age I was at that time.

 

I still, surprisingly, had no B Symptoms 2 ½ years on from diagnosis, but my lymphocyte counts had doubled twice during that year, and I’d read that even doubling once in a year is grounds for concern. The hospital thought treatment was looking inevitable by this point, so they now had this further diagnostic test done.  When the genetic mutation status test results came back and I’d had to relay the updated prognosis, that felt like a real blow - as though the cancer were suddenly rampaging, despite what had seemed like early predictions to the contrary. Of course, this is a very complicated disease, it’s near impossible for a layperson to grasp all the implications and I probably didn't ask enough questions at each juncture, but when we panic we lose our clarity of thought and tend to use our imagination in unhelpful ways.

Managing expectation is a big challenge for clinicians, and with hindsight I realise that just a few years before that time the hospital staff couldn't have even dreamed that the treatment I was now on would be available. But it's natural for people to build up hope that they're in the group in which nothing will develop - especially with a disease like this, which many people can have while still essentially looking and feeling pretty well - if they're offered that hope.

I do, on reflection, believe that members of the public could grasp this 'disease of thirds' concept, and that we would all be better placed to contextualize the probabilities in the CLL equation if this were explained to us. I think it’d be helpful to many if a number of the latest videos about the incredible advances in the science were made available to patients who wanted to gen up on as much as possible, as well.

I spent that “Dark Night Of The Soul” weekend intensively researching online. To illustrate the point I’ve just made, one apparently recent article dated 2016 - just two years earlier - indicated a far worse prognosis for people whose (IgHV) genes are unmutated. But then I came across this one which indicated that all need not be lost: https://www.oncotherapynetwork.com/news/ighv-mutation-status-does-not-affect-cll-survival-among-ibrutinib-treated-patients

Nowadays it’s a known fact that your IgHV status is irrelevant where targeted drugs are concerned. This in itself is an incredible clinical breakthrough indeed.

FLAIR is a Phase 3 Randomized Clinical Trial (RCT). Most of us who are not medically or scientifically trained would assume there’d be a placebo arm in any RCT. So it was interesting for me to learn that when researchers are comparing treatments so different that you’d immediately know which one you are on, things don’t have to be done this way –like, in this study, where they’re comparing a purely oral treatment (pills each morning) with treatments involving chemotherapy and intravenous immunotherapy.  As soon as you are randomised to a treatment arm, you’re told what it is. For me, it felt like a relief to know this – especially when I was told I’d been randomised to my first-choice option. It makes you feel much less of a guinea pig. Finally, I could get down to focusing my research on this one pioneering approach.

I had been fortunate enough to have gained access to the cutting-edge ibrutinib and venetoclax combination treatment through taking part in the trial. These currently phenomenally expensive drugs haven’t historically been available to anyone in the UK not on a trial until recently. But I learned that those who - as things currently stand - are unable in the first instance to routinely access these particular drugs (eg because they can’t access a relevant trial or get randomized to another option) can now be routinely prescribed them as a 'second line treatment'. This felt really encouraging to know. Of course, any participant in the trial could have been randomized to one of the alternate treatment pathways and you have to mentally prepare yourself for this. I felt this discovery would have been something to hang on to if I hadn’t drawn the longest straw, though. It's also heartening to remember that other revolutionary treatments approaches, such as CAR-T, are being honed all the while, and just as each biological being necessarily presents with a different disease 'fingerprint', as it were, treatment is becoming ever more closely tailored to each unique manifestation of the disease too.

The Leeds-based FLAIR trial has been modified since its inception in spring 2014 as a result of developments in the USA CAPTIVATE Phase 2 trial, which is running concurrently.

 

With one original treatment path, or 'arm' - the ibrutinib and rituximab combo - closed because it had fulfilled its recruitment quota, since July 2017 FLAIR has been offering:

·         FCR - a combination of chemotherapy and immunotherapy (current standard NHS frontline treatment),

or treatment by either

·         ibrutinib alone (Treatment “I”),

or

·         ibrutinib  (called 'imbruvica' in the States) and venetoclax combined (Treatment “IV”). That involves, specifically, taking ibrutinib alone initially, then venetoclax is carefully added into the mix after about eight weeks.

I started on the trial in October 2018, as I said.

It sounds hard to believe, but within the first week of the ibrutinib regime we noticed the swelling abating.

The dose was three tablets (400 mg) of ibrutinib first thing in the morning, before breakfast.

The nodular swelling progressively abated – it just seemed to melt away – and, miraculously, within a month or so things looked and felt exactly as they had done before it had all started. It wasn’t just the visible swelling, of course. There were also balloon-like soft lumps in my armpits, that felt like a second pair of breasts over to the side and had begun to impede my arm movements and feel quite achy, and nobbles that had developed in my groin on either side and felt like giant walnuts to the touch.

Venetoclax has to be painstakingly added in, in a rigorously tapered fashion, several months later over a five week period involving numerous hospital visits. The idea, certainly historically, was to keep the majority of people in hospital overnight for a few days at the outset, to be on the safe side. But I believe this may not be seen as so necessary nowadays, with the fantastic results both this trial and CAPTIVATE (US) are returning – over 70% in complete remission within a year of starting treatment. So long as the ibrutinib has been given for a sufficient time, it will have done its job and eliminated the bulk of the lymphocytes from the lymph nodes around the body.

When this has been done, starting the extremely potent venetoclax – particularly building up the dose slowly – once staff are satisfied that the patient is safely established on the target maintenance dose of this additional drug (420 mgs a day), you continue taking this medication each morning at home - this time after breakfast - and it gets to work in earnest, targeting the residual rogue lymphocytes accumulated within your system.

I was fortunate enough to meet the trial's criteria - just! 

- and also to be randomised to "I and V": effectively hitting the jackpot, as we saw it. You had to have at least one node measuring over 10 cms, and I had just one that measured 10.5!

I felt further encouraged and bucked up by a comment made by the retired oncologist who had looked after my father 25 years before, at a time when the science was in its relative infancy. He told me:

"You're on the very best treatment available in the UK at this time".

If you've done any googling on the subject at all, you’ll have noticed that there's a genuinely skilled international community of CLL expert-patients who have clearly looked into every aspect, and permutation, of the disease and all possible treatments available in minute detail. There's a lot of technical language used and a painstaking, academic approach to understanding the predicament and options of as many patients as possible is evidently being employed by many.

For a while, I tried to make notes of all that seemed relevant to me and to get my head around some of the information. But in my case many of the discussions proved to be irrelevant.

It all seemed so complicated and - as with many others, I imagine - at that time I just needed encouragement to hope about my own situation, really.

That said, I discovered increasingly fascinating articles and film clips (always possible once you discover new key words and search criteria) once I was able to narrow my search criteria down, and was in a more focussed, constructive mindset, and gained a rudimentary understanding of what the newer drugs were aiming to do: enough to have given me the desire to sign up for the clinical trial and the hope, once more, that things might be able to go in other than an inevitable downhill direction.

 

In my experience, if you ask experts to explain these drugs work in simple English, they can't. So, this is how I framed it in my head. It may be over-simplistic and naive, but it helped me. The issue is one of cell death. CLL cells are rogue white blood cells. The white cells normally fight infection, but the cancer cells are imperfect copies that don't function as part of the immune system. Normally cells need to die routinely, and CLL cells are not doing that but, instead, begin to proliferate in an out-of-control way - as they’re enabled to be effectively immortal - reproducing exponentially. Ibrutinib binds a substance that's getting in the way of this happening (BTK, an enzyme that controls the rate of cell death). This enables the cells to die naturally again and very soon dramatic results can even be witnessed externally as swollen glands swiftly melt away.  

 

For some reason, though, ibrutinib alone is not as effective at getting at CLL cells hiding in the bone marrow. The rationale for bringing in venetoclax at this stage is to inhibit a protein (BCL-2), that is also stopping cell death by masking CLL cells - preventing them from being picked up by the immune system, which is always looking to kill anything that's a threat to the body. Venetoclax is, similarly, a super-charged force, flushing the remaining lymphocytes progressively out the bone marrow into the bloodstream where they are instantly decimated by an immune response now able to access and recognise them.

 

Because people tragically died in the early phases of development, venetoclax is consequently now administered in a different way. The doses initially given to patients in the Phase 1 trials were way too high. This resulted in such a dramatic reaction in the body - where condensed toxins, created from the simultaneous demise of far too many cells at once, overwhelmed the filtering systems in their bloodstreams and clogged up their arteries. Their systems simply couldn’t cope. For this reason, now ibrutinib is always brought in first to clear bulky nodal disease before venetoclax is even started, and then it is introduced really slowly and patients are intensively monitored on the first day or two of treatment.

 

When about to start the second drug, and unsure what to expect, this short film really helped me. With its clear, unpatronizing explanations and dramatic, memorable imaging, it engaged and encouraged me. We discovered it shortly before treatment started. It’s only 5 minutes' long, and is in two parts. The first describes and illustrates how cell death usually comes about, and the last two minutes (Part 2) show how venetoclax mimics natural functions impaired by cancer, saves the day and - miraculously - brings about the required end result: https://www.youtube.com/watch?v=tzwaPWElklo

Personally, I had an incredible experience on the I and V treatment arm of the FLAIR trial. 

Pretty much from the outset I felt well, and after a few months I also looked as I had done before – despite the fact that my unmutated IgHV status would have meant my chances weren’t great even just a few years previously. Fantastically, it seems as though the majority of participants on the IV arm of the trial have had a similar outcome.

 

As my research became more focused, I was constantly reminded how important it is to focus on very recent developments and discussion as current cutting-edge science in the CLL arena will now look very different again from the way it did at the time I’m writing about, or even the way it looked last year. The uncertainties and risks we perceive to be inherent in a course of treatment is enhanced where Conventional Medicine is concerned because we are aware of, say, the toxic nature of traditional cancer treatments (chemo- and radiotherapy) and clinicians are legally obliged nowadays to tell us in detail about every last thing that could go wrong, or that has affected any others. As ordinary members of the public we can find it nigh-on impossible to sift amongst the mountain of information and come to a clear decision about whether to enrol on a trial of new treatments; whether even to embark on a treatment at all. It’s not that the hospital staff don’t care, but nowadays we’re all supposed to take responsibility for ourselves and it’s assumed we’re capable of making our own decisions where furnished with relevant information.

 

I was struck by Atul Gawande’s comments in Being Mortal. I did read it, and it proved to be a really exceptional book! He reflected that he, his father and mother (all three of them doctors) were in a consulting room with a specialist at a climactic point of his father’s life-threatening illness. None of the three of them could make sense of the situation or work out what course of action made the most sense. His father was a consultant in his own right, but he had never been on the other side of things himself and, Atul says, in this situation:

“Making choices somehow involved filling in the gaps, and he filled them in with fear”.

 

He went on to speak about there often seeming to be only two types of consultant – the paternalistic (“with the air of authority, self-certainty and being busy with things to do”) and ‘the informative’ type – the one who overwhelms you with information that you’re in no position to either assimilate or process. In the end, Gawande’s family were fortunate enough to meet a consultant he describes as ‘interpretive’ who saw himself “not as the commander nor a mere technician in this battle, but instead as a kind of counsellor and contractor on (his father’s) behalf”. While, if taken at face value, current legislation decrees clinicians play a merely objective role in overseeing test results and treatment choices and plans, kindness cuts through our fear and enables us to see the wood from the trees and recover our equilibrium and capacity for self-agency a bit more.

 

I remembered how keen my dad was to take part in a clinical trial. But for him, at that point, there was no time left. I have been aware all along that, while no one knows what causes CLL and it seems as though there could be a number of reasons why it develops, there can be familial links between people who contract B Cell cancers. It has been my great good fortune not to have needed treatment until a few years ago, at which time I was able to try these drugs and they seem to have had a miraculous effect. I’m always aware that my own daughter might present with this disease when she’s older, though, and – while we are all delighted that the results of the trials are proving so encouraging – no one knows what long term effects these substances might have as they have only been used to treat blood cancers for the first time very recently and, for CLL, more recently still.

 

I know that many, and possibly the majority of, people who end up needing treatment for CLL have much more confronting situations to deal with than me. Yet at any time before, my prognosis (because of my unmutated IgHV status) would not have been encouraging either. For this reason, I regard myself as living ‘on extra time’ (as in a football match). I am well aware that my additional lease of life is a bonus and, regardless of what might happen in the future, I know that, as the result of this trial, ibrutinib and venetoclax have restored my life for now in full, glorious technicolour. So I’m “ahead of the game”, as they say in the States.

 

In the end, the decision to go on the trial was not a difficult one.

 

I’ve always been bemused by the saying “Better the Devil you know than the Devil you don’t know” – after all, when you know the situation you have in hand isn’t great, why should an alternative necessarily be worse? I’m an optimist and, when there’s at least a 50/50 chance of an improvement, I’d always take a chance on it. FCR is known to take a considerable toll on the body, and in people with unmutated IgHV it’s also known to have very limited positive effects. There’s also a good chance it will be superseded very soon by new treatments and that the stressful ‘Watch and Wait’ period, in which the disease is currently (and counterintuitively) allowed to carry on and get into gear, will no longer be part of treatment plans. This approach was established for a good reason, as when rituximab was the new kid on the block, it was imperative not to begin treatment too soon as its efficacy would time out. The novel agents don’t seem to lose their effectiveness over time, though, and it’s clearly not a good idea to let a disease get into gear if that can be avoided.

 

The aims of this trial seem to be, to see whether the other treatment arms are more effective than FCR (the current NICE ‘Gold Standard’) as a first line treatment. If determined to be so, my understanding is the chosen arm/s should then replace FCR as the Gold Standard, be funded by Government and made universally available.

 

And then, on the experimental arms, to see:

·        -  how many people attain MRD Negative status on each arm

·        - whether and when people restart the treatment.

·        -  (where they do) to determine how ‘treatment holidays’ – periods of time on and off the treatment – might work.

·       -   how many of those people go into indefinite remission (i.e. potentially, could this be seen as a cure. This would be a massive deal, but it seems to be on the table here).

At the time when it was necessary for me to decide which treatment route to take,  my cousin - a few years younger than me and still in her mid-50s - contracted Motor Neurone Disease. Again, a condition seeming to manifest out of the blue. She diagnosed herself through researching material on the internet, but desperately hoped her conclusions would be proved wrong. To everyone's consternation the diagnosis was finally confirmed, though. The medical profession could do little to mitigate her suffering and it fell to her family to take control - to support her in living the rest of her life in as dignified and engaged a manner as possible. Since her death just before Christmas, groundbreaking new research has come to light that offers real hope that that disease too will become manageable sometime in the not-too-distant future. So it feels as though there's some hope going forward. But the timing of the breakthrough was of no help to my friend.

My feelings about having been, comparatively speaking, unaccountably blessed in my own situation came down to a mixture of guilt (that I was being effectively treated, and visibly got better as she steadily declined) and relief that CLL is now a field of burgeoning hope (while, tragically, the science around MND has until now languished firmly in the Dark Ages). Our comparative positions really gave me a yardstick for contemplating my own situation, though, and enabled me eventually to experience for myself and others going forward the excitement that is palpable within the CLL treatment field as we go into the third decade of the 21^st century. It truly feels as though I was magically transformed back to my pre-disease self as, I understand, countless others with similar conditions can now be.

Advances in science are only possible where people are prepared to take risks and give consent for their progress to be observed in real-time. At a phenomenal cost, the drugs and the treatment that is afforded us in the UK by our wonderful National Health Service are an incredible gift, unavailable in so many countries around the world. We are certainly aware of our privileged position at times like this. In exchange for my restoration to health (for now, at least) it feels good to have been able to be involved in a research study and to contribute, through taking part in the trial, towards ensuring ever-improving treatments will become available for an increasing number of people both now and for the generations who come after us.

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Some additional resources -

If you have found these reflections helpful, here are a selection of video clips that have encouraged and informed me. Most of them are pretty recent, from 2019 onwards, as the newer information - as the science develops in leaps and bounds - is much more complete, definitive and encouraging. Many of us need to feel we can actively engage in the daunting choices that face us, and when we focus on helpful information it tends to link us to more of the same (we find more relevant search terms, etc). 

In terms of understanding and ranking resources, I tend to take a consensus view. Where the opinions of those one respects concur, and they collectively refer to facts and trusted resources, that seems like a good signpost to the uninitiated. I hope these film clips will inspire you to dive deeper into the rich well of information and encouragement that CLL treatment is now inspiring. In my own internet research, I got most encouragement and elucidation from googling the latest videos on the drug combinations that were relevant to me - putting the current year in the search criteria, to bring up the most up-to-date results. 

Video clips in chronological order:

2017

 

It was particularly elucidating to listen to Dr William Weirda speaking at ASCO just at the time when I needed to decide whether to go on the trial: https://ascopost.com/videos/2018-asco-annual-meeting/william-wierda-and-julie-vose-on-cll-results-from-the-captivate-trial/  4 mins Weirda

 

And here Dr Eradat speaks more recently about the CAPTIVATE data and what has now been established, in July 2019: https://www.youtube.com/watch?v=ivX_STngXjE 2 mins Turkish? Dr Erdat

 

This discussion about venetoclax use in community settings, recorded at the ASH conference back in 2017, reassured us that the ramp-up regime subsequently instituted as standard is ensuring great results:

https://www.youtube.com/watch?v=r538iWmSpzs  5 mins

 

2019

 

More recently, Dr Constantine Taw summarized encouraging results from the CAPTIVATE trial - that are revolutionary for anyone contemplating or embarking on the I and V combined treatment regime - in these five short clips of film, each less than two minutes minute long, shot in December 2019: https://www.youtube.com/watch?v=rydSWCqDzug 2 mins

 https://ecancer.org/en/video/8518-ibrutinib-plus-venetoclax-for-the-first-line-treatment-of-cll-sll-results-from-the-captivate-study 4 mins Constantine Taw

 

You can clearly see the contrast in the manner of this expert within two years in the CLL research story. Professor George Follows speaks with excitement about the treatment possibilities being developed in 2017: https://thepatientschannel.com/video/e5nt9avsy4k-promising-treatments-are-coming-a-message-to-lymphoma-and-cll-patients/   1 minute

But just see and listen to him here:

https://www.youtube.com/watch?v=gvuoKgnP5Sk  2 minutes, 40 seconds

There’s palpable animation and excitement about developments he clearly hadn’t envisaged happening by this point in time. Filmed at ASH 2019.

 

I’ve continued watching videos and trying to keep up with advances discussed at the annual ASH (American Society of Hematology) and ASCO (American Society of Clinical Oncology) conferences, and was interested recently to stumble on this recent discussion concerning diagnosis of CLL/SLL. The first doctor is well aware that the majority of his patients experience a lot of the thoughts and feelings I’ve just discussed and consequently opts to get all the tests done, correctly surmising that those who will prove to have a more challenging journey would rather know what they’re up against and be able to mentally prepare themselves and their families and those whose condition is not so serious will feel the relief of knowing where they stand too. Clinicians then know where to focus their energy too.

 

I considered calling this piece of writing ‘Not just CLL’ precisely because people – and particularly friends with medical knowledge – are apt to say “At least it’s only CLL.” In this 8 minute video, the first two doctors to speak discuss the importance of early comprehensive testing not just because for a small proportion of patients CLL turns out to be a highly concerning disease where many even of the newest treatments that are generally well-tolerated will not work, but they explain that they understand the stress patients tend to feel when they don’t have a clear idea of what they’re looking at in terms of severity of disease, probable timing and duration of treatments, etc. It seems to be the general consensus, anyhow, that having as clear a map as possible of the terrain at the earliest opportunity best equips both those planning how to approach things (the consultants and their teams) and patients who need to orient themselves and their families: https://www.onclive.com/view/a-rapid-shift-in-treatment-for-cll  December 2019 8 minutes

 

And last but definitely not least (the opposite, actually!), a more comprehensive discussion by one of the top experts in the field can be found here: http://videopodcast.researchtopractice.com/chronic-lymphocytic-leukemia-william-g-wierda-md-phd  Aug 2019 William Weirda    1 hr, 15

Thanks a lot for visiting my site and reading this. 

If you'd like to, please link with me on Twitter: @NickyHay4Blog or Facebook ('Nicky Hayward'). I'm up for discussing of this and everyone else's experiences too :-)

Finally, so you can compare, here are photos shot a) before, then b) when my lymphocyte count was soaring and c) after ibrutinib treatment pics (all taken in the space of about nine months in 2018):