At the end of cycle #6, I first had an appointment at the National Amyloidosis Centre at the Royal Free Hospital in London, followed the next week by the usual haematology clinic appointment at the end of cycle # 6 and prior to starting #7.
The NAC appointment was spread out over two days, with the SAP scan (to map out the distribution of amyloid protein deposits) on the second day (having been injected with the tracer SAP isotope on the first day). No great changes there, in that there’s been no progression in the amyloid deposits since the last SAP scan that was done in May 2012. Equally there’s also been no reduction in the amyloid deposits, though that’s to be expected as in the interim my free light chain levels have been at elevated levels.
The discussions with the consultants at the NAC and with the Registrar at Southampton General the next week were fairly brief in the event. Despite the slightly bullish attitude of my last post about upping the thalidomide dosage, the consensus view from the medics was to be cautious because I’d reported some hints of neuropathy, albeit extremely slight (just an occasional hint of slight numbness in a couple of finger tips). As they stressed, although mild neuropathy might be expected to reverse somewhat, nerves in general are not good at repairing, so they are wary of pushing the thalidomide dosage too hard.
The Registrar in Southampton did however comment that at a review meeting prior to my appointment, the haematology team had commented that I was generally tolerating the treatment very well so far. Given that peripheral neuropathy is a relatively common side effect of both Velcade and thalidomide, the fact that I’ve got to cycle #7 (of Velcade, with thalidomide since cycle #4) with so little neuropathy is quite a good performance.
Of course as I documented in overly-scientific detail in my last blog post, my free light chain levels still have some way to go before they’re down at what could be termed a ‘normal’ level, though I was pleased to hear at the Southampton appointment that the last two free light chain measurements made by Southampton have been ~2500mg/l and ~1250mg/l (as compared to ~6000mg/l and ~5000mg/l measured by the NAC). It just goes to show how different the values can be when measured by two differently calibrated assays.
So signed off for cycle #7, with the thalidomide dosage held at 100mg/day. On we go…
Not really been a great amount to report over cycle #6. Just before starting this cycle I discussed how the treatment was treating me with the consultant at Southampton General and although I had generally been feeling pretty good, still going running, still working to a relatively normal level and so on, he thought it was sensible not to up my thalidomide dosage any more for cycle #6 because I’d reported to him that I have a faint hint of tinglyness (I wouldn’t go so far as to call it numbness) in the index finger tip and thumb tip of my right hand. Some neuropathy is not uncommon as a side effect of having Velcade and also of taking thalidomide. On my first cycle on thalidomide (cycle #4) I was on 50 mg/day. For the next (cycle #5) I was moved up to 100 mg/day. The consultant said to me that before I’d walked in the door he was considering putting me on 150 mg/day (apparently 200 mg/day is the limit).
I wonder now that I’m nearly at the end of cycle #6 (next week being the “rest” week and cycle #7 starting the following week) if perhaps I didn’t overplay my description of the fingertip tingling, but in reality I don’t think I did. Funnily enough I tend to be pretty honest and upfront with my medical practitioners these days (not that I was terribly cagey and devious previously, but I think you get what I’m saying) and I just told him like it was. I get the impression that the doctors are quite careful to watch out for any signs of neuropathy, as I read that it can take a while to build up and also can take a while to regress, even after lowering the dose. In extreme examples the effect can be partially permanent.
Having said that I think that the fingertip tingling has actually reduced in the last couple of weeks, to the extent that it’s virtually non-existent now (though I need to be careful because I’m writing this on the second of my two steroid days this week and everything seems better when you’re on steroids…). But I do think that it’s really at a level now where if I weren’t looking for it, I wouldn’t notice it.
More pragmatically, it may be time to weigh up some pros and cons. Although my free light chain levels have started to come down now that I’m on the thalidomide, they still have quite a way to go before they are anywhere near a “normal” level (for a healthy individual). Although a complete reduction to that kind of level from this induction stage of chemo may be rather optimistic, the aim is to get the levels as low as possible with the induction chemo before progressing to the high dose treatment and ASCT (autologous stem cell transplant). My understanding is that the overall prognosis after the high dose / ASCT is better, the better the effect derived from the induction chemo that preceded it. You can see the overview of the progression of the values from the following plot:
The dip down to ~7000 mg/l on 26/9/2012 is viewed as an anomaly – probably of the measuring technique, rather than a real variation in what was going on in my blood. Moreover the scientifically minded amongst you will recognise that the data points should really have error bars (with respect to the measured LFLC concentration – I’m pretty confident about the dates) and indeed I’m told these could easily be +/-50% when measuring concentrations at these high levels. But ignoring the anomalous measurement, it’s easy to see that it was really only when I switched from CVD (cyclophosphamide / Velcade / dexamethasone) to VTD (Velcade / thalidomide / dexamethasone) that real headway started to be made.
And in particular for the scientifically minded amongst you, have a look at the same plot with a logarithmic scale for the LFLC concentration:
Lower right in the plot I’ve added a band to show where a “normal” range of lambda free light chain concentration in the blood should be (i.e. between 6 to 26 mg/l). I think that illustrates that there’s a little way to go yet. By the way, for those of you who are self-confessed non-scientists (you know who you are), especially those who take a particular interest in my well-being, don’t be too freaked out by the second plot. A logarithmic scale can be a little deceptive if you’re not used to looking at them – they’re useful when trying to show on the same plot two ranges of data values which have quite a difference in size. However, it also has the effect of greatly compressing large changes in values towards the upper part of the plot, so it artificially makes it look like my values haven’t budged much at all.
I’ve probably overplayed the data analysis card by this point, so to scramble for the take home message: look at the first (linear scale) plot and think of the aim being to get the LFLC concentration as low as possible (ideally near as dammit to the bottom of the plot). Which brings me back to the question about the thalidomide dosage. Although it’s working, there is still a way to go with getting the LFLC level down and seeing as whatever neuropathy I may be encountering is so mild I’m currently thinking that upping the dose to 150 mg for the next cycle would probably be worth doing. I can always switch back to 100 mg if I notice that the neuropathy is picking up, but I would like to see those levels coming down just a little bit faster. And of course, otherwise I’m feeling very well: I did two 5 mile runs last week, and even the Tuesday (non-steroid) one wasn’t too much of a battle (though Friday was lurvely); I cycle to work every day (most days with my son in a child seat to drop /collect at nursery); and I’m working almost full time (allowing for regular medical appointments).
It’s good timing to be thinking about this, as next week I have another 2-day appointment at the National Amyloidosis Centre at the Royal Free Hospital in London. A “two day appointment” makes it sound more dramatic than it is – it’s really just two 2 hour appointments on consecutive days. The reason for the split is to be given an injection on the first day of a radio-isotope of a protein which temporarily binds onto amyloid deposits around my body, so that it has time to find its way round my system by the second day when they post me into a scanner (in which I fell asleep last time) which shows where those amyloid deposits are (the “SAP scan”). I’ll also get to discuss my treatment with one of the consultants there, who are serious experts in my condition, and they will doubtless have some advice about whether to push the thalidomide dosage now or not. Then the following week, shortly before starting cycle #7, I have my next appointment with the consultant in Southampton, who’s ultimately the one who writes my prescription for the next cycle (and in fairness is also pretty damned knowledgeable about my condition too – sorry Dr J, didn’t want to cramp your style).
So, more updates to come about how the London appointments next week and the Southampton appointment the week after go, and what the plan is for the next cycle. Watch this space. Phew, that turned into a longer post than I was expecting and it’s now 2.30am, but that’s days on dexamethasone for you. Well done and thank you if you’ve read this far.