‘I’m sorry, you don’t qualify for the CAR-T study. Sorry you had to come all the way down here to hear that news…’
That was the the ‘Fellow’ I met with. He continued, ‘…our pathology report says this is ‘follicular lymphoma, grade 3a’, which means there is no CAR-T option available at this point’. I was stunned. This was not the conversation I was planning to have.
So the pathology report conflicted with Kaiser’s. For some reason on the call Friday the nurse told me I qualified for the CAR-T study and that’s why I should come in Tuesday. Based on my read of the clinical trial I took that to mean I had a DLBCL, or at least existence of 3b cells. Then the study coordinator called me and we discussed the trial details under that assumption. There’s a saying I am finding increasingly helpful: do not attribute to malice that which can be explained by incompetence.
Then I met with the primary doctor. VERY sharp guy. He opened up the fire hose, speed talking immunology like we (Michelle and Lua were there) were PhD’s in it. I didn’t follow every mechanistic detail but I got most of it. And I appreciated that as I took it to mean he was leveling with us. This stands in stark contrast to what can often feel like party-line medical answers from other doctors.
The issue, in part, is that the programmed cell suicide pathway is disrupted on these B-cells; when a signal is sent that it’s time for a cell to die (called apoptosis), they don’t listen. As a result these cells will accumulate in the body. At what rate they accumulate remains unknown. In contrast DLBCL/3b cells actually divide more rapidly. Aggressive Follicular it seems is kind of a grey zone – scarier than follicular 1 or 2, but less of a Russian roulette treatment path than DLBCL.
Tracing this back to the original diagnosis, the current thinking/most plausible explanation for the current diagnosis is that the original tumor (before any chemo) was a mix of 3a follicular and DLBCL. Stanford actually re-classified the original Kaiser pathology report as 3a + DLBCL (it was originally 3b+DLBCL). Regardless my treatment was the correct one though we’ve been saying it ‘wasn’t successful’. That might be a bit unfair given what we’re seeing now. What we think the latest biopsy shows is the first-line treatment was successful in killing the nasty DLBCL, but left the slower growing 3a follicular cells which aren’t responsive to that treatment. Apparently this is not an uncommon situation.
Your eyes may be glazing over at this terminology but it’s a clinically important distinction to understand. To remind you, ‘follicular’ lymphoma is the slower growing, somewhat less aggressive version as compared to DLBCL (see the sketch). The ‘3’ means it’s more aggressive than 1 or 2, so it’s on the high end of the indolent/slow growing type. And Follicular lymphoma is not curable – not now.
His recommendation, incredibly, is to watch and wait. He doesn’t think I should undergo treatment this very minute. He said I should do a scan in 3 months (that’s 3 months from the last scan date) – which is a few weeks from now. In his view the risk/benefit of undergoing increasingly toxic chemotherapy and stem cell transplantation doesn’t make sense given this report. He then went on to describe the side effects and long-term issues with those treatments. As just one example, when I asked about CAR-T cytokine storm disproportionately impacting young more than old – turns out that’s true. Scary. He said “you’re 41 years old. You have a beautiful daughter. I want to hold off putting you through this if we can.”
Or, translated to Yiddishkeit: Mazeltov! You have an incurable form of cancer.
How am I holding up emotionally?
I’ve got whiplash. I entered that meeting considering poison A vs. poison B. Instead I got an entirely different recommendation to sit tight a few weeks, to wait for that next PET/CT to tell us what the disease is doing. So, again, I have conflicting data points. If I allowed my mood to reflect the circumstances I would be a disaster. I love the idea of awareness as reflecting the space one has created between stimulus and response. I’ve been trying to pry that space wide open lately and not get perturbed by information: good or bad. Here’s an exercise I do sometimes: I imagine these bits of information as an object, like a storm cloud or a blob floating in the air above my head. And it’s charged – it has energy.
Energy itself is neither good nor bad on its own, it’s what it gets used for. I look up, like a boy to a balloon and consider how that energy is affecting me. I try to keep it simple: am I going towards that energy, or away from it? Then I peel it back another level, why? And then another, why? Until I feel like I’m at the root of what’s causing that feeling. What’s in it? It’s not perfect but I find it a helpful practice to get perspective. Left unchecked, thoughts can be pernicious things, can de-rail a mind. In particular I find that non-helpful narratives spring like weeds. I need to be a vigilant gardener, lest they take over. For example, as a father, it’s hard not to envision what life might look like for my kids if I weren’t around, if this thing got me. It’s horrifying to consider and it’s so easy to get enamored with those kind of ideas, to let them take you down. I try to root that stuff out without mercy. The trick is to be aware of them in the first place which is not so easy.
Swinging on branches
After the appointment we met a friend for lunch. As we sat outside on the quad at the nearby Google campus on a beautiful day I was overcome with the idea that I was at that moment living on a highly improbable branch of possible futures. If for a moment we assume Stanford is right then here’s the most likely alternative reality that I’d be living had I not sought all these other opinions…I’d right now be undergoing 6-8 weeks standard of care second-line treatment focused on targeting the wrong cells (DLBCL). That would probably not work because, as I understand it, follicular 3a type aren’t responsive to that treatment. Then I would do a PET/CT to see if it was successful in curing my (incurable) cancer. Another week of waiting. Then, when the results returned negative my hopes on moving to the autogenic transplant would be dashed – no passing through the second gate toward curing this. Cue feelings despair, devastation, hopelessness. If the disease showed progression I might need to get another biopsy to see if there was any mutation – it’s not uncommon for follicular lymphoma to mutate into DLBCL (that’s likely what happened at the outset). Now suppose for a moment that a few weeks/months/years down the line that happens again. What then? Well, then I’d be in a position whereby I’ve exhausted two of 3 (currently) available bullets to treat this (First line – done; standard of care – done; CAR-T – still available). All because of the wrong diagnosis. I’d be in a position of yet more stress inflicted on me and my family, reduced optionality, and with elevated toxicity inflicted on my body.
Who do I believe? What’s my next move? There are, broadly, two pieces to consider. The first is aligning on the diagnosis, then, what to do about it. These seemingly minor differences in diagnosis suggest wildly different approaches and it’s frightening how different the recommendations are given that it feels like we’re splitting hairs on terminology.
I need to know that Kaiser is aligned with Stanford. And I need to cross check all this with UCSF and Dana-Farber for additional confidence. The original recommendation to press ahead with second-line standard of care still lingers. Taking news at face value hasn’t been my approach so far no matter who is delivering it – good or bad. So even if the Stanford pathology report is to be believed (and I want to), there’s still a very real possibility that I travel down the standard of care path in the immediate future. It might still be the right move. Here are the most obvious scenarios by which I could see this happening:
- Stanford reverses their recommendation. Stanford hadn’t yet received my PET/CT results from Kaiser. They need to review that information and follow up with me.
- Second opinion disagreement. I’ll validate this second pathology report with my ‘panel’ of expert doctors. There could of course be sufficient doubt about this diagnosis and a recommendation to bias towards supreme vigilance. I’m considering getting a third pathology report if there’s sufficient tissue to do so to bump my confidence in the Stanford report. Or perhaps a 3rd pathology report would agree with the original? I can’t help but still feel uncomfortable that this may be a sampling issue whereby they sampled a part of the tumor, and then are staining a sample of that sample. This may be overkill but seems a reasonable step to take at this point.
- Next PET/CT scan shows progression. If I do wait and watch this thing, my next scan could show disease progression. Might that suggest the pathology is wrong and that aggressive cells are still present? Not sure yet how to think about that piece, without doing another biopsy (ugh!). Either way the assumption this is 3a/slow growing would seem debunked at that point and would I think suggest the standard of care route.
- Transformation. As noted above it’s not uncommon for follicular lymphoma to transform into DLBCL. This could be happening now, could start weeks/months/years, or might never occur. From a quick read of the literature that likelihood increases 2-3% per year, not sure if it’s age or grade dependent.
So, immediate next steps:
- Ensure Stanford views the PET scans from Kaiser and sticks with this recommendation. That seems critical to rounding out the picture.
- Ensure Kaiser aligns with Stanford on this diagnosis and treatment path. The doctors hadn’t spoken last I checked but both agreed to connect and discuss.
- Align with UCSF, Dana-Farber on second pathology report and treatment options/risks to various strategies. The conversations I had previously assumed a different diagnosis.
- Run a 3rd pathology report? Schedule next PET/CT in a few weeks?
- Finalize answers to open questions, concerns and decide on the path forward.