I’m slightly delirious so you’ll have to excuse this update as I have the Jackson Five song on repeat in my head. I think this part of the trial is not so much a test for reactions to Venetoclax, as a test of human endurance/water/sleep deprivation torture – I have now not had more than 45 minutes sleep for 48 hours and I’m really feeling it. My trial nurse Sam worked a 16 hour shift yesterday so I can’t complain as I know he’ll be feeling it today too. I’m so lucky to have him, he’s so calm and, most importantly brilliant with needles, we’ll be into the 100’s of “just a wee scratch” by the time we’re through. This one on one care could become a bit addictive too. All these vials needed to be filled within 24 hours of taking the drug (needles are not so addictive).
Diagnosed at 38 a few days before Christmas 2011 with my then 2 year old daughter on my lap, I was told I had Chronic Lymphocytic Leukaemia (CLL), an incurable disease where the average patient with my prognostic markers could expect to live for 5 years. The average patient, however, was a 70 year old man. A year later I became so sick I required treatment and had 3 cycles of a chemotherapy known as FCR. My remission only lasted 6 months and it looked very much as if I was going to have to have an allogeneic transplant using stem cells from a donor to save my life. This is a difficult treatment and, while, if it works the benefits are long term control of the disease, the risks are high and mortality rates and quality of life issues made this something I wasn’t ready for. I began a global search for an experimental treatment after realising that my options in Australia were limited. In November 2015 I began a clinical trial at Barts Hospital in London of two drugs which have not been used in combination before – one of these is ABT-199, now known as Venetoclax, which was ironically invented in my adopted hometown of Melbourne. I feel very privileged and grateful to be on this trial and this blog is designed to help other patients who may choose this path down the track. It will be a bit technical for my non amateur haematologist friends but the CLLers it’s aimed at will understand.
I’ve now finished the 1st cycle of Obinutuzimab – they do choose some strange names for these drugs, ABT-199 is now called Venetoclax and referred to as VEN for short in the scientific papers, George Lucas eat your heart out.
I had another 1,000mgs on day 8 and another 1,000 yesterday on day 15. Side effects were minimal. The steroids on day 2 made me sweat a disgusting sweetcorn smell for a few days and I was relieved when they dropped those for days 8 and 15 and the anti-emetic made my bowels stop working – TMI? (I’ve been told I should enjoy that given how active they’ll be when I start the ABT-199). Yesterday I got away with having the Obinutuzimab on its own with no ‘roids or anti-nausea drugs and boy do I love the piriton appetiser – really relaxing, wish I could start every day with an infusion of that.
So now that I’ve officially been debulked how am I doing? Well first of all pictures tell a 1,000 words so let me show you how I have no visible lymphadenopathy left.
I had a full examination today and there are still some palpable nodes in various spots but they are all less than 1cm which is a big relief. This is my latest blood test too.
Although I’ll be having another 4 cycles of the Obinutuzimab over the next 4 and a half months I feel like it’s probably done as much as it’s going to do on its own….and it’s now time to bring in the big guns of ABT-199 aka my new friend VEN (he sounds a little Swedish doesn’t he?). So let me tell you about this amazing drug which I’ve spent the past 18 months trying to access. It’s been a long time love affair and I have to say now that we’re about to consummate our relationship I’m starting to get the wobbles.
ABT-199 is the most exciting weapon in science’s new arsenal against CLL (and several other blood cancers for that matter). For the geeks such as myself you should know that it targets a protein called BCL-2 which is over expressed in these cancer cells – by entering the cells and shutting this off it causes them to die and the effect is almost instantaneous.
Within hours of popping the pill it goes to work and cancer dies in massive amounts (apoptosis is the official term). The exciting thing is that, unlike chemotherapy, it is targeted therapy so the side effects are much more palatable. All but one that is. Sadly in early phase 1 trials of the drug (and we really are still in early trials – I’m in phase 1b) the immediate impact that it can have on the cancer cells wasn’t fully appreciated and at least 2 patients died in the US of what is called Tumour Lysis Syndrome. I heard that there was a third death in Australia but I haven’t read this in any of the published data. Tumour Lysis is where the body can’t process the amount of dead cancer cells quickly enough and it leads to kidney and ultimately heart failure.
Shockingly two patients died within hours of a dose escalation and, for as long as others like me enter these trials and others later benefit from this amazing drug, they will be constantly in our thoughts. We lab rats who enter Phase 1 trials are brave but we’re also very sick and have run out of options and this is the only way we can access cutting edge therapies.
I knew one of the patients who died via the CLL forum, a man called Randy Shirley who was not much older than me, with a wife and children and a zest for life who also blogged his journey and had been a huge advocate for other patients. He was interviewed by Andrew Schorr on Patient Power shortly before his death and Andrew, the beneficiary of a clinical trial himself, paid this tribute to him
Randy was at a centre of excellence for leukaemia trials in the US. His last post was a photo of the 12 pills he was about to take for his dose escalation along with the comment that he was the first patient to ever take such a massive dose. Within hours he had died at home and his death shocked the whole patient community. The trials were immediately suspended and the protocol changed to include more hydration, more hospitalisation and lower doses of the drug. While we mourned Randy, and my thoughts are still with his family, we were also scared that this might impede the approval of the drug which offers so much hope to those of us with this incurable disease. 53% of patients on one of the combination trials of ABT-199 with an older version of the monoclonal antibody Rituximab/Mabthera have no detectable cancer – that is an astonishing figure for a relapsed and refractory group of patients who were almost certainly facing death without this drug. Patients are going from hospices to being cancer free after this treatment and that’s unheard of in our disease.
Pharmaceutical companies need patients like Randy and myself to get their drugs approved but patients like us also need it to give us a chance at getting through this disease.
So, having said all that, Tumour Lysis Syndrome (TLS) is now my most immediate fear. Because I’ve been debulked and my White Blood Count is lower the danger shouldn’t be as great, but today I had a blood test which showed an elevated creatine level in my test from last night which is a warning sign for kidney damage. I am drinking so much water but have now stepped it up even more and my test from lunchtime today came back normal but it was a bit of a fright for me.
I will be admitted to the hospital on Monday afternoon for IV hydration overnight and will take the first VEN pill on Tuesday. They’re starting me off at 20mgs and I will take that daily for a week before I’m escalated to 50mgs for a week, then 100, 200 and finally onto my ongoing dose of 400 mgs a day. 2 hourly blood tests will follow and they’ll be particularly watching my potassium and creatine levels which is what tells them TLS is happening. My understanding is that the renal team will be on standby if I do start showing signs of this and they will quickly start flushing me out, I’m assuming with dialysis, to help process the drug and dead cancer out of my system.
It’s all a little scary and I know, having travelled around the world to meet my new love, I’ll be a lot happier when I know the only thing he’s going to kill is my cancer. Sometimes knowing too much is a bad thing but that’s what informed consent is all about.
I’ve had a few emails asking me how I have ended up in the UK from Australia (and thank you for the lovely feedback) so now is probably as good a time as ever to share the story of how I met Professor Gribben from Barts.
I have two wonderful specialists in Australia, my original haematologist Dr Melita Kenealy from Cabrini Hospital, who diagnosed me in December 2011, and my prospective transplanter Professor David Ritchie from the Royal Melbourne, who was the first doctor to use the words potential cure around 4 months later. I trust both of them with my life and, despite my type A control freak personality, would go along with their treatment decisions in a heartbeat. The fact is I delayed having chemo beyond the point I should have and when I finally did have FCR wished I’d listened to them and had it a couple of months earlier such was the improvement in my quality of life (they were good enough not to say we told you so!). When my disease relapsed this year to the point that I required further treatment I was inspired by one of Australia’s most successful businessmen Ron Walker, who had travelled to the US to enter a clinical trial for aggressive melanoma. You may want to read the article which triggered my pilgrimage –
My feeling was that, I may not be rich, but if there was a better treatment option open to me overseas that wasn’t available in Australia then I would move heaven and earth to access it. So with my doctors permission I travelled to the US in April to get an opinion from Professor Thomas Kipps at the University of California San Diego. Professor Kipps is one of the world’s foremost CLL experts and my visit coincided with a patient conference organised by the CLL Society and the CLL Research Consortium to give patients the latest news on clinical trials. It was perfect timing for me and I appreciated my Australian doctors humouring me by agreeing to let me explore other treatments before we proceeded to transplant (this is still the only known potential cure for CLL).
Professor Kipps’ opinion was that I shouldn’t yet have a transplant and that I should have some novel therapy to buy me some time before a good clinical trial opened up in Australia – indeed Professor Ritchie had been exploring what was available for me to use as a bridge to transplant before I left Australia. Professor Kipps also urged me not to consider a clinical trial in the US for if anything were to go wrong, being uninsured, I could end up with medical bills running into the millions.
The next day I went to the conference. Jetlagged and totally exhausted I crept into the back of the theatre just as a Scottish doctor was giving his presentation. Funnily enough I took a photo.
I asked the patient next to me who was speaking and she said it was Professor John Gribben from St Barts Hospital in London. After he finished the Professor walked up to an empty chair beside me in the back row and sat down – you can see from the picture how many people were in the room! I was wearing a toy koala on my jacket as there were people trying to meet up with me and he asked if I’d travelled from Australia for the conference and if I was a carer. I said no I was a patient and he said if I didn’t mind could I tell him how old I was when I was diagnosed – I said I was 38 and he asked if I’d had treatment. I told him I’d relapsed early from FCR and he said so you’re here looking for a clinical trial. I said I was and he said but you’re British – I have a great trial for you if you can make it back to London. That is how a chance meeting led me back to Blighty. We spoke after the conference and the Professor said he hoped that there would be a better option in Australia which wouldn’t mean so much upheaval for me and my family but added that he would get his trials nurse to forward all the details to show to my doctors. That night I flew to another patient conference in Niagara Falls organised by the Canadian CLL patients group where I met Professor Michael Keating and we talked footy (another of the world’s leading CLL experts based at MD Anderson and an Aussie to boot).
Everything moved so quickly after that. The first person I caught up with was Dr Constantine Tam, one of our leading CLL experts who is also responsible for bringing a lot of the international clinical trials to Australia. He said that, despite Australia having more experience with ABT-199 than anywhere else in the world, the trial in which I was most interested would not be opening there. The only way I could access the drug would be to enter a phase 3 study where it would be randomised against more chemotherapy – had I not already failed chemo I would have jumped at this opportunity – it’s called the MURANO trial for the Aussies reading this. After going through all my options with me he reluctantly agreed that the best potential treatment for me (and please note this won’t be the same for everyone else given how heterogenous this disease is) was the London trial. He added that there was no rush as my disease was fairly stable and I would actually need to have more progression in order to qualify for the trial. I then saw Professor Ritchie and I was convinced he would try to talk me out of it, but he actually agreed with Dr Tam, adding that he thought ABT-199 was a great option for me and that this potential new therapy combining it with Obinutuzimab could be the only alternative to transplant for me. If it didn’t work as well as he expected then at least he knew I’d be happier to proceed to transplant knowing that I’d thrown the kitchen sink at this disease (my words not his!). If I didn’t make it onto the trial plan B had to be boarding a flight back to Australia and letting him get rid of my dodgy immune system and replace it with one that actually recognised the leukaemia and would start attacking it.
So here I find myself. The hardest thing is being separated from my children but their father and I agreed that it was best for them to stay at school in their routine, particularly as I would be spending so much time in hospital. They all came over a few weeks after I arrived for their spring school holidays and will return in 3 weeks time for their long summer break and first wintry Christmas.
It was my daughter Natasha’s 6th birthday today and it’s the first time I’ve ever been away from any of them on their birthdays. Thank goodness for technology – it was a delight to watch her opening her presents via FaceTime and I wasn’t too down knowing that I’m here to make sure I’m around to see her open them for many more years to come and will spoil her rotten with a Mummy and me day when she gets to London.
My mother travelled from Australia to look after me when I started treatment and her phone did a great autocorrect last week when she told my sisters on our whatsapp group page that I had a glow in my cheeks and was looking so much better since I started doing pirates. As interesting as I think that might be, and who knows it might even help my recovery, she was actually referring to my new found love of pilates.
My friends all chipped in to give me a wishing well to spend in London when I left Australia 3 months ago (thanks again girls) and I finally found something to put it to good use with a course of private Pilates sessions on reformer machines. The sense of well being and strength I’ve found from this has blown me away – I can see why my friends have become addicted to this wonderful workout.
Today, two days after my first treatment my South African instructor Karen took me through a gentle workout – actually she wasn’t that gentle! It felt good to get my body moving again and I was perspiring much more than usual – I think the obinutuzimab is still in my system. She could see the changes in my body since last week – my abdominal lymphadenopathy had given me a bloated look. I’m hoping the strength exercises will help my poor veins recover too before next week’s treatment and it’s great to leave the studio with that “I’m very much alive” feeling. Now time for a long hot soak in the tub and a lie down!
After my adventures with the mouse in the middle of the night, I’ve been a bit tired today. Popped into the hospital to have a blood test at lunchtime and picked up the results from 10pm last night which showed my White Blood Count is now 11 and my Absolute Lymphocyte Count is 2.7 which is in the normal range. My haemoglobin has dropped a little to below normal (10.8) which could also account for a bit of the tiredness but it’s not enough to warrant a blood transfusion thank goodness. Felt a bit sad helping the nurse find a vein – I am starting to look like I’ve been injecting drugs into my veins for years – heroin chic I think not. Maybe that PICC line might be worth another go. No more pricks so to speak until Tuesday and tonight is one of those nights I really miss in the UK – it’s bonfire night. I often wonder what primitive tribes would make of our tradition of ferrying a stuffed effigy of one Guy Fawkes around in a wheel barrow to throw on a bonfire and dance around chanting while celebrating his burning. Home firework displays are illegal in Australia so I wish the children were with me to see the view beneath a leaden sky from the 23rd floor of my apartment near Barts tonight.