Obi-wan Kenobi

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

http://www.patientpower.info/blog/patient-power/2012/12/20/the-sudden-death-of-randy-shirley-a-leukemia-loss/

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.