My Brentuximab Fling

Clinicians and patients differ in their opinions about Prednisone. Clinicians seem to view the drug as a last resort, a temporary fix to be used sparingly for a short duration. As short as possible. We patients, however, love the stuff. It makes us feel wonderful. We can frolic in the sunshine, climb hills – slowly, but we make it – talk incessantly and feed constantly. In short, we feel well and like to stay on the steroid for as long as we can.  Oh there are some negatives; degrading quad muscles, degrading biceps, minor sleep impairment, facial puffiness, and some funky liver enzyme readings, but did I mention I sunshine frolicking? I was allowed Prednisone over the Christmas period. It was wonderful. It even offers me temporary reprieve from my rigors. Simply wonderful.

My ICE relapse complicated further treatment plans. Actually, it put a complete halt to them. Other options were required. The easiest was to use a different strain of chemo, but I am kind of running out of those. I have been exposed to most chemo classes, therefore the chance that a different agent will actually help me is limited. The resistant cells will merely grow stronger. I think there is one chemotherapy class that I have not yet tried. Another option was a targeted chemotherapy drug called Brentuximab. Hodgkin’s cells express a cell marker called CD30. It sticks out on the cell like a little flag declaring its individuality from those surrounding it. Brentuximab contains an antibody complex that targets CD30. The drug floats around the body searching for any CD30 flags. When it finds one, the antibody attaches to the cell and pumps it full of a chemotherapy agent. It is a lock and key approach. Imagine you are standing in a hotel corridor with a key but no room number. The only way to find out which room you are in is to try all the locks. Oh look, the key fits in this lock, this must be your room. But wait, someone else is already in the room. Well you’d better punch them in the face, Bruce Lee style. That is pretty much how Brentuximab works.

This drug had been around for a few years now, but it is usually only used for patients who relapse after their autologous stem cell transplant. There have been a couple of trials using it on patients pre-transplant, but they are not sufficient for the New Zealand drug agency, Pharmac, to automatically fund Brentuximab. Strangely enough, the New York blogger I mentioned, probably a year ago, was a participant one of those trials. It is a small Hodgkin’s world. Brentuximab was the drug my consultant wanted to use so he asked Pharmac to fund it for me. This required a bit of research on his behalf, a named application followed by a cost benefit analysis. I don’t know if they attached a personal reference and a photo as well; it did sound complicated. For my non-New Zealand readers Pharmac is deemed a bit of baddie. They only make negative headlines over here. Nobody wishes to be denied treatment for financial reasons, and media outlets, well, they eat those stories up. In a Christmas pantomime, Pharmac would be booed on entry.

The application was two weeks into another limbo period. One would think that with all my prior practice in waiting, my patience would now be pretty good. It is not. Well it is to a certain extent. Tell me there will be no news for a week and I will be fine for that week. But once those seven days elapse I start to become restless, distracted, cantankerous. Initially the wait for Pharmac was to be three days, then seven, then ten. I did not expect the funding to come through. I expected them to reply “Try more chemo. If that fails get back to us.” In an odd ironic twist, if they didn’t respond before a certain date, I was going to require the chemo anyway. One can’t help but smile at that. But Pharmac responded in time. They responded with a yes, which leaves me a little confused – do pantomime villains actually have layers? Our families were ecstatic with the news, but I must confess I felt indifferent.

The ten day wait for Pharmac was nothing compared to the wait for the actual drug. There are no stocks in New Zealand. An Australian company said they could deliver it to us in a week, with it arriving Christmas Eve. I was to attend the day ward the Tuesday after Christmas ready for my Brentuximab. But it hadn’t arrived. It was “in transit”. Transit from where, no one knew. They weren’t even sure if it was in transit to Wellington, or to the Australian company. Just that it was in transit. For the next two weeks we spent our days waiting for a phone call announcing its arrival. Eventually we got a call “Ah it has left Australia”. What? It was only now in Australia? A call a few days later “It is in Auckland. We will try to get an overnight courier, so come in tomorrow afternoon.” It turns out it was held up in customs in Auckland as it cost (far) more than the GST import threshold, and customs would like some tax please. I am not sure how that was resolved, but I know it infuriated my clinical team. It took three weeks for the Brentuximab to get to Wellington. Some say it was sent by kayak.

During this waiting period Mike and I binged on the second season of Fargo. It was a bit fucked up. Not the scene where they bury a guy alive in molten asphalt, I can handle that, but the thirty year old wife who has lymphoma and is on experimental drugs. And we know she dies. We know because Molly’s mother was dead in the first season, and she died of cancer. Ah but we’ll just let the senseless killing around her, around us, distract us from battles that need to be fought, fought without killing anyone. That and Kirsten Dunst’s performance. Which was awesome. 

Anyway, after my Penelope inspired patience (and weeping), and some excitable distractions courtesy of a surprise visit by my Scottish sister, I was ready for this Brentuximab shit. I was all psyched up, prepared for all the worst side effects, and it was totally anti-climactic. A little fuss and excitement was had in the day ward, but physically nothing. Nausea: nil. Cell counts: completely normal. Hair loss? Nope, more like super hair growth, which is good because I was looking like a humanoid cylon prototype, with tubes under my skin and a shiny skull. So there were no side effects. Maybe I could imagine some fatigue. But that could also be the steroid withdrawal. And the infusion only lasted thirty minutes. I had it in the day ward. No overnight stays.

Three weeks of Brentuximab, a week off, then three further weeks. That was the plan. After the first three weeks I was finally fever free. My heart rate was a charming 79 and I was starting to feel much better. Granted I still had prominent lymph nodes in my neck and groin, I was still experiencing night sweats, and my spleen was causing me grief, but overall I felt nearly well. My consultant allowed us an anniversary trip, which we’d kind of already partially booked. The trip took us to the northern Coromandel, completely off the grid. The plans were for walking, swimming (paddling for Liv), nature and books. Maybe even some beer. And no contact with the outer world. We were to forget our current worries.

My rigors started on the second day. The lymph nodes burst through later that evening.  You can ignore, or at least weakly justify, the changes for a couple of days, but once the rigors become regular and the fevers creep higher, well we knew, we both knew, what was going on. It was fortunate that we were completely alone, in our hired bach, sitting on the deck listening to the kiwi and the morepork chat to each other – the morepork always has the final say – as it gave us a peaceful setting to contemplate my fairly obvious relapse. I set myself to weeping. I was glad that we were off the grid. It is difficult to correspond with people when everything is getting worse and our future is becoming uncertain and bleak. Since November we have had three weeks, those first three weeks of Brentuximab, where we have definitively known what was going on. So if you’re wondering how I am, be rest assured that I am shit. Except, of course, for that one Thursday when I saw my consultant and I was well. There is not much point in asking how I am. It is strenuous and exhausting responding to multiple messages.

Ok, so it wasn't all doom and gloom

The day before we left my temperature shot up to 40°C. We made an obligatory call, which went unanswered, to my clinical nurse who is holidaying in the North of England. I hear it is charming there at this time of year. Really the phone call was so we could claim that we hadn’t broken all the rules. Only the remoteness, the untreated drinking water, the unpasteurised cheese… They were not overly impressed at the day ward when I admitted the 40°C fevers.

I have started Prednisone again. I pretty much begged them for it. It doesn’t seem as effective this time. There has been no frolicking, and although the rigors have gone, the fevers still remain. In my gut I had believed Brentuximab would work. But it didn't. It is another limbo period treatment wise. We don’t know what the next step is. No one does. Emails are being fired between here and Australia, opinions are being sought, but a decision is yet to be made. I now know that these limbo periods need to be covered by steroids because Liv’s body and mind and husband cannot deal with long frequent rigors. They are debilitating. And, during this current period of high grade fevers, Wellington decides to throw out a fortnight of scorching weather. But at least now I am now grateful for the wind.  

        

     

If all goes according to plan

So. It has been a while since we last spoke. As you may have noticed I have retracted into my shell, occasionally sticking my irritable neck out for food and water, but generally content to sit in my own darkness, insulated from the outer world. I think it is my bald head. It kind of makes me look like a turtle. I am pretty distracted and this entry has been the victim of severe procrastination so I am just going to launch into it, skip the descriptions Wellington’s wind, of my fragile emotional state, and just get the words out there. I don’t particularly enjoy writing in this manner but let us see how it goes.

Some weeks ago, after my second round of ICE, I had a CT scan to check my lymphoma status. The results were good; I had achieved a partial response to ICE chemotherapy, only the nodules in my lung remained. BCSH guidelines (yes, I have read them) state that a partial response is required to proceed to the next treatment stage. Mike and I shared another public peck at the good news and preparations for the stem cell transplant began. It was scheduled for December 23^rd, a perfect Christmas present. I had only one round of ICE remaining.

I shall deviate here slightly to nerdily describe the stem cell transplant progress. It is better defined as a ‘blood stem cell transplant’, you know, to remove any controversy. The idea is the bone marrow is stimulated via high dose G-CSF injections administered over a ten day period. This means two injections in the gut each morning. By about day seven the bone marrow is producing so many cells that they do not have time to differentiate within the marrow, so they just remain as stem cells circulating in the blood. These ‘mobilised’ cells are then ‘harvested’ by apheresis: blood leaves the body from one tube, undergoes centrifugation, the stem cells are collected, and the blood is returned back to the body through another tube; a continuous process with only a few hundred milliliters of blood leaving the body at one time. It is similar to dialysis. The collected (haematopoietic) stem cells are then frozen. This is a preservation process as the high-dose chemotherapy (BEAM in my case) is so toxic that it kills the bone marrow and damages stem cells. It also melts away any residual tumours. After the BEAM, the frozen cells are reinfused into my body, take about seven to ten days to work their way into the bone marrow and Hey Presto! I am cured. If all goes according to plan. The stem cell mobilisation was to start the day after my final ICE infusion.

I check into the haem ward cranky, as usual, for my final round of ICE. As I have previously mentioned it is a three night incarceration that I am never eager to attend. And the final round was crap. I was irritable day one, threw up for three consecutive hours day two, refused all hospital culinary delicacies from there out, and spent day three trying to focus on objects situated directly in front of me, failing, and falling asleep. At two a.m. in the morning of my final scheduled night as an inpatient, my temperature spiked above the dreaded 38°C. I am usually pretty clued up when it comes to my fevers, I know when they are coming on, I know how long it will take for my temperature to reach 38°C, and I know when to take paracetamol to calm the bastards down. This particular fever, however, took me by surprise. I knew I would not be discharged that day and I was pretty bloody angry about it. The doctors termed me ‘unwell’, infection was presumed, and broad spectrum IV antibiotics began with a disclaimer: we may not be able to begin your stem cell mobilisation tomorrow if you have an infection.

Well, isn’t that a fun thought to try and get your head around, when you are stuck in a room with a stranger, a stranger who has many different snores (so many I could not count each noise), trying to comprehend that your schedule, the schedule that had taken three months to prepare, could be thrown out the window because of one stupid temperature spike. I had prepared for many scenarios where the transplant would not go ahead, but I had not prepared for failure before the process had even begun. I was angry, down to the depths of my stomach, and there was nothing at all I could do about it. Relief came the following day, a Monday, when the regular haem team were on and assured me that the stem cell mobilisation would go ahead. It was the most reassuring gut injection I have ever received.

Despite the continuous IV antibiotics, my body feverishly pottered along. A couple of tender lymph nodes bulged from my neck, a couple more sprung up in my groin. The fevers became the predictable events I remembered; a rigor one could set a watch to. These were starting to resemble disease fevers rather than infection. This thought comforted me; if I don’t have an infection then they will let me out of hospital and I can at least feel shitty in an environment of my own making. I decided these words of wisdom ought to be conveyed to the haem team.  Unfortunately, they did not share my enthusiasm. I should not be displaying symptoms of disease. If I was, then the transplant would not happen and plans B and C would not only need to be devised, but also actuated.

And it was about then that I completely lost my shit. I had, externally anyway, remained calm when around the clinicians, hid my fears, my worries, and had just concentrated on the information they divulged. I even offered them a sly joke or two. But, at that moment, I lost it. My tears became as uncontrollable as my fevers. It turns out that further relapse was also omitted from my list of possible failures. There was still the slight, very slight, possibility that an infection was causing my symptoms and, as I was losing my shit in more ways than one, further tests were performed. I vaguely recall cheering "I have c.diff, I have c.diff" from my hospital bed and fist-bumping my nurse as he wheeled me into isolation. I am not sure how much of that memory is actually fever. Probably most of it. The general sentiment of the moment remains: I was happy and the clinical team were ‘cautiously optimistic’. The persisting IV antibiotics had wiped out my microflora, my good little bacteria, leaving c.diff to run amok. But it did not take long before I realised that the infection was a false hope. A helpful little night nurse even told me that one doesn’t get fevers with a c.diff infection. I do not know if she understood the implications of her statement.

I remained in isolation to protect my fellow patients, received the daily G-CSF jabs and plunged back into lachrymosity, the tears only amplified by my frequent fevers and general pessimism. Harvest day was looming. The haem team continued to bathe my cells in IV antibiotics. If I did indeed have some superbug with freakishly good hide-and-go-seek skills, they did not want it interfering. Interestingly, if my disease had relapsed it would probably not affect the harvest. Hodgkin’s cells rarely make it into the actual blood, so my stem cells should be mutation free. I know I have used the word ‘rarely’ there. I will emotionally deal with that possibility at a later date. A far later date. Anyway, the only ominous factor, aside from those aforementioned, was the absence of bone pain. I had been on double dose G-CSF for eight days without the slightest orthopaedic discomfort. There is a minimum cell count (CD34) required before the harvest will proceed. That magic number is 20. (They never told me the units, and I confess I never asked.) My count, on the day scheduled to be harvest day, was 2.5. The harvest is planned over a week, I still had four days remaining to reach 20, so really it was no big deal, but having been in hospital for eleven days, and with all the setbacks, and the frequent toilet breaks, I did not have the mental capacity to deal with a number as low as 2.5. So I do you know what I did? I am sure you do. Yup, I cried. I ignored all of Oasis’ advice, and cried my heart out.

The following day, however, I was roused by unrelenting skeletal agony. And I smiled, a sick masochistic smile, as I informed the clinical nurse of the substantial bone pain. She shared my excitement and rushed to tell the team. I imagine she burst into the office, hands in the air singing “She’s got bone pain!”, the remaining nurses and doctors of all ranks tossing their papers in an act of jubilant celebration.  Hmmm, perhaps that was just another fever. When she returned I was back to tears. I was no longer enjoying the pain. My count that day was 10, but they decided to hook me up to the harvester anyway with the hope of collecting the required volume of cells over two days rather than just one. They did not want to risk losing any of my circulating stem cells. The panic was unnecessary. The next day my stem cell count jumped up to a whopping 45 and I was hooked up for a further six hours. I will tell you about it sometime. But not now. This has gone on far too long already. The stem cell harvest is done, they have double the cells required, frozen in a protective pool of DMSO, safe for the next five years.

Harvest time

So that just leaves the fevers. In the final days of this horrendous episode I had a CT scan. The results were damning. The lung nodules had grown, further nodules had popped up in my spleen; pretty much all of my lymph nodes were enlarged. A biopsy wasn’t even required. In the three weeks since my last scan I had once again managed to relapse, relapse with a vengeance. This means, of course, that of my three doses of ICE, one worked, one was dubious, and the final was utterly useless. All it did was increase my reliance on donated red blood cells and platelets. In July I just wanted to make it to Christmas without a relapse, instead, I have relapsed twice. Yes, I am a bit bitter.

My discharge came suddenly. I could not be discharged to the cancer accommodation we had been staying at for the last four months as I was still symptomatic for c.diff and my fellow immunocompromised inmates could contract it from me. Mike called his brother and we made a rapid transfer to his place, and, ah, we kind of haven’t left. I am not going back to the cancer accommodation. It is existence, it is not living.

As the clinicians discussed plans B, C, D, F and probably Z, I was left to battle the fevers myself. I had a column of cuts running down my thumb from the paracetamol packaging. The fevers became more and more frequent and debilitating with each passing day. I was a broken mess, and all the King’s horses and all the King’s men were struggling, really struggling. They have since put me on Prednisone, hence the hyperactive nature of this post, which usually works for ten days. I’ve been on it sixteen now and it is starting to wear off, a few symptoms are sneaking through, but it has given me a fortnight of faux energy and actually feeling alive. Obviously, the transplant did not go ahead, but plan BCDFZ has been written, in pencil, and further treatment is imminent. We are just not sure quite when. There have been, and still are, a few complicating factors, but I will go over those in a later post. I don’t have the energy to discuss them right now. We will be in Wellington for a few more months yet. After a year of treatment, I find myself back at the start.

  

A statistically bad chemo

I think the less I say about my last chemotherapy experience the better. Even the minimal information I do intend on parting with will probably gross you out. Basically, there were too many bodily fluids flowing from too many orifices. There are certain biological functions that, as an adult, one assumes they will always have under control. Ah, welcome to hospital! Here is a bag for your possessions, and another for your dignity. You’ll never get the latter back. The majority of the three days was spent playing trial and error with food sources in a vague attempt to keep said sources in my stomach. The error rate was high. Eventually, I stuck to minute sips of water. Despite my vomiting, shame, and general sentiment of doom and destruction, it was difficult to feel sorry for myself. The guy through the wall from me would heave for an hour straight. I, at least, threw up my pathetic meals rather quickly.

We are not entirely certain what lead to such an extreme decline in my chemotherapy tolerance. There were two variables, which I know is terrible science but I cannot help that now. I am beginning to think that biology is more of an art than a science. I will use this to justify my multiple variables. Anyway, where was I? Variables, right. I had begun a rigor-fever cycle a couple of days prior to this round of chemo. The fevers were never massive, they were deemed low-grade (which I believe means less than 38°C) by the medical staff. This time the rigors were blamed on the lymphoma despite my full blood count resembling an infection. I may have questioned the numbers. Twice. I still suspect I had an infection. The rigors do not matter much now, they have resolved, but a week ago they wore me out dreadfully. I was like super tired before chemo even began. 

The second variable involves the anti-emetics, which were altered slightly. They withheld the steroids. Initially I was happy with this move. I do not care much for the side effects steroids have to offer me, namely the pressing need for two a.m. snacks. Unfortunately, here I need to swallow what little pride I have left and confess: chemo is easier with steroids on-board. I feel better throughout and I feel better afterwards. Perhaps this may be deemed performance enhancing, but seeing as I am not a Russian track athlete, I don’t think anybody is going to mind too much. The day after my discharge I spent twenty hours horizontal, fighting, not really fatigue, but some haze between the real word and unconsciousness. Aside from a vague nausea and a relatively vocal stomach, I was not in any real discomfort, my eyes just refused to remain open and I could barely move. Next time I will take my dexamethasone like a good little girl and, perhaps, have days of production rather than destitution.

I have written more than I intended about my last chemo. It is a period I care to forget about. The topic I had actually intended on writing about is statistics. This could be an opportunity for you to stop reading. Things may get a little dark from here on, and the word ‘statistics’ has been used so, naturally, I expect some of you have drifted off to sleep. Also, I may mention particular statistics that you may not wish to know about. I kind of wish I did not know. I have stopped asking. So if you want to tag out right now I really don’t blame you. In fact, I admire you for lasting this long. Chocolate fish all round.

In July, after I received my unfavourable news, I was forced to think a bit. People talk about glasses and their perceived volume; is the glass half empty or half full? Most would probably decree that I was a glass-half-empty type of girl. To be honest I never really put much thought into the matter until I was, well, forced to. Upon reflection, I realised I was the type of girl who obtained, through certified channels, the exact capacity of the said receptacle, analysed the volume of the liquid within the receptacle using a traditional measuring cylinder, confirmed the result using a weight based technique (verifying the equipment's calibration status in the process), and had therefore discovered that the liquid occupies 47.25% (+/- 0.25%) of the volume of the receptacle; so indeed the glass is more than half empty. What I am trying to say is I like to know all the facts. And then I will overanalyse those facts.

In early August I became a little obsessed with statistics. I listened to the doctors, I read the textbooks, the papers, the review summaries; I knew the feedback cycles, the treatment regimes, the drug interactions. Then, sometime during my August-September diagnosis period, I developed a thought pattern, probably incorrectly, that medicine as a practise was entirely statistics. The case studies, clinical trials, meta-data analysis, create these numbers and percentages that are then used to treat patients. This is why my diagnosis process was so thorough: “It is very rare, Mrs Stocker, for you to have relapsed or refractory lymphoma given your clear scan in April.” It is like 8% rare or something like that. Not really rare, more statistically unlikely. I had a 92% chance of achieving remission and I blew it. Somebody needs to make up that 8% and once you find yourself in that minority group you cannot wish yourself out of it. As soon as you do that you are effectively wishing it on someone else. I would never wish this on anyone. For the 92% who made it through I am happy for you, but also a tiny bit jealous.

Having been blown away by stupid minority statistics, it is difficult to take the rest seriously or optimistically. Apparently 50% of patients are successfully harvested. Given my rapid relapse, that figure drops below the half mark; somewhere between 25 and 50%. So I had a 92% chance of remission and now, with some extremely positive thinking, it is around 40%. I began shying away from success stories, as if those whose treatment worked chipped into my 50%. It is not that I didn’t want other patients to be successful, I just didn’t want to hear about it. This is, of course, absurd logic. Each individual’s case is mutually exclusive, statistically not even medically. Medically each case is like an ENZA orchardist comparing apples with apples. I started to get cranky. What does ‘successfully harvested’ even mean? Do age, previous medical history, or charming personality effect these statistics at all? Is there a time frame? Is it six months? Three years? Five years? I would be happy with five years, hell, I would be happy with three. What happens if I am unsuccessful? Actually, I know the answer to that one: more treatment, worse statistics.

Eventually I became overwhelmed by statistics. 50% of salvage chemotherapy patients present with neutropenic fevers. 1% will die from these fevers. Less than 1% of patients fail to have a PICC line inserted. 99.9% of female salvage chemotherapy patients over 25 years of age become infertile. 50% of patients discuss fertility preservation options. 50% of patients who discuss fertility options actually take up the options. 10% go on to use the stored material. It is ‘unfortunate’ but not ‘unheard of’ to have needed multiple biopsies pre (or mid) diagnosis. At least they did not attempt to quantify that one. I have a scan coming up that will alter my statistics. Not the scan itself, but its results. Over the last couple of months I have stopped reading the statistics. I cannot change them and, although there is no point in dwelling, I did tend to fixate on them a bit. Ok a lot. Now, in order to make an informed treatment decision, I am required to read the science and statistics once again.

In here, this cancer institution, this day ward, this haematology ward, we are all unfortunate statistics. Not one person I have met has obeyed the textbook. Bone marrow transplant patients have had failed stem cell transplants. They were happy with the time they got. In the community the people one meets are usually survivors. Here, they are sufferers and complications. And there is always someone more worse off than me.

Some days I get hung up on the statistics. They are totally beyond my control and I think that is what bothers me; there is nothing I can do to change which side of the statistics I fall on. I get frustrated, sad, and angry. Other days I find it all oddly liberating. That life plan that always niggled at the back of my mind, a career, a house, some kids, a few cats, a handful of chickens (they would get along with the cats just fine), that plan doesn’t exist anymore. It is not even possible. I mean, Piper would never tolerate a chicken. During the days of liberation it feels like there are no expectations of me, like the only thing I have to worry about is being on the good side of statistics, the statistics I can participate in, but cannot control. It is odd to have these contrasting days. I would say that there is a strong correlation between how I am feeling physically and how I am feeling emotionally. So is the glass half empty or half full to me? Well, unless we are talking about a beer jar, I really do not give a damn.