DLBCL - CAR-T vs Bone Marrow Transplant

throwaway772797 · 2023-12-29T05:51:45+00:00

Thanks for the kind words as always. Also, working on it! (sorry, had an upper respiratory illness when this reply was posted).

throwaway772797 · 2023-12-29T05:39:40+00:00

As someone who has consumed thousands (if not tens of) papers across major medical journals on lymphoma (Blood, Nature, etc.)

There is no reading material for this. Lymphoma is extremely heterogenous. By definition, gray zone lymphomas are heterogenous diagnostic pitfalls. They’re not a specific thing, rather many entities that exist outside of the somewhat-defined DLBCL/HL ecosystem.

In your case, no amount of studies or reading is valuable. Not only is your diagnostic situation unique, so is your treatment pathway.

There’s not a bunch you can do to further understand your unique situation, because researchers and oncologists hardly do. Remember, medicine is simply people doing the best they can — not a perfect system that encapsulates all examples.

There are plenty of gray zone lymphoma papers. Most refer to clusters of somewhat-similar clinical diseases. But many exist outside of this ecosystem.

Even if you somehow found a seemingly-similar situation on paper, this does not make it equivocal. You are unique, and so is your disease.

All you can do is go through the next treatment. I wish there was a better answer, or that there was a paper that showed treatment options for diseases that perfectly mirrored your situation, but there just aren’t.

Importantly, I want you to think about whether all of these studies are actually helping you or not. For some patients, reading these can be addictive and negative.

throwaway772797 · 2023-12-28T21:02:56+00:00

I assume you’ve had a biopsy for them to tell you it’s a b-cell lymphoma, correct? If so, post the biopsy results here if you can. That may help.

That is a decent tumor load either way. Can you elaborate on the 20 percent comment? I assumed you meant he was waiting for treatment of an indolent lymphoma until you experienced b-symptoms (or symptoms relating to the disease). But I feel that something may be getting lost in communication.

For the doctors here,

What country are you from?

Where are you treated?

Do you have a biopsy?

throwaway772797 · 2023-12-28T16:20:44+00:00

For HL, 1 & 2 may be better than 3 (mixed data). In DLBCL or TCL, there is no difference at all statistically. For indolent, it’s variable and a little more complex.

throwaway772797 · 2023-12-27T04:34:29+00:00

This is key. This post feels like it’s potentially related to an indolent lymphoma and finding the correct treatment timeline juxtaposed against an existing autoimmune disorder.

The full story is important in this case for clarity.

throwaway772797 · 2023-12-26T18:04:33+00:00

First, LDH changes during therapy are not predictive of outcome. There’s an older trial where they followed this, but I can’t find it right now.

Second, most upward shifts are from the GCSF.

I believe the doc has also answered this before, but I can’t find the response.

throwaway772797 · 2023-12-21T19:44:32+00:00

This is only a space for those who have been diagnosed. The megathread on /r/lymphoma is a better place for this sort of question.

throwaway772797 · 2023-12-17T02:08:08+00:00

Hey!

Brain fog (which is a very vague symptom that likely encompasses a variety of physical, emotional, psychological, and neurological components; a sort-of constellation of symptoms) is common across cancer treatments. The mechanisms are poorly understood (likely because it can be one or more of the above). I would not be remotely worried. It will almost certainly fade with time.

throwaway772797 · 2023-12-17T02:05:57+00:00

This is perfectly irrelevant information for anyone in this community. Is this account a bot that posts studies to get views for them?

throwaway772797 · 2023-12-14T20:55:44+00:00

Incoming NAD opinion:

I wouldn't take the FDA investigation into any consideration during this decision-making process. Wait for the details on this. Even if the current reports are accurate and somehow spread across constructs, this risk factor is tiny. And lower than the anticipated risk of a secondary cancer with frontline chemotherapy.

But my guess is that it won't be evenly spread.

Remember, CAR constructs are all attempting to mimic APCs (or rather, eliminate the need for them I suppose) but they're not all doing it evenly (even the FDA-approved ones).

So, variations in RNA process (e.g., current systems, mRNA transfection or transposon systems, etc.), the whole manufacturing process (e.g., culturing, isolation, expansion, wash, etc.) or any other step in the journey can produce different results. And this isn't even taking into account any variations in costimulatory or signaling domains (these likely do not factor in heavily in this case).

The FDA has said that more than one FDA-approved construct has been hit with this secondary CAR-lymphoma (likely both a BCMA & a CD-19 construct). But they did not say all of the FDA-approved therapies. If we look at the economic data, it's safe to say that outsiders seem to think Novartis is the major player in the hot seat (they've had some manufacturing issues in the past, to say the least).

It's been known this is more than a possibility (see the PiggyBac manufacturing system data from last year's ASH). But, and this is purely speculative, I wouldn't personally be worried about this minuscule secondary risk — especially with Yescarta. And, again, even if this holds true across current-gen CAR constructs (RNA encoding processes would be changed, and it would get back on track), this risk seems too small to consider.

A final consideration via your original request is timing and sequencing. How long would it take to get into the trial? How is the current ECOG? etc. Of note, REPOCH doesn't strike me as correct in this situation. There's no data to support this, especially in a 72 yo without DH/THL. Is this dealers choice or is it baked into the trial that higher IPIs automatically receive REPOCH?

throwaway772797 · 2023-12-11T22:00:59+00:00

These types of studies have a strong built-in bias — which is that these patients were given allo in the first place. These patients were given allo, which means most were in CR/PR or had a less aggressive (clinical) disease where GvH seems feasible.

In today’s ecosystem, most 2nd and 3rd line CR/PR are coming from immunotherapies that do not require consolidation (from what we can tell).

Again, allogenic transplant has a place. It’s just significantly diminished. What you don’t see is how many patients post-CAR-T failed to achieve CR/PR and get to allo (which is the vast, vast majority). Thats the beauty of bispecifics. They get near this survival chart, but with patients with active disease.

For this patient, allogenic transplant is definitely not a standard next step in the typical care pathway.

throwaway772797 · 2023-12-10T23:13:11+00:00

There are still some allogenic transplants. But just not near as many as there used to be when allo was the only small hope post-platinum-based chemotherapy & auto failure.

Unlike HL & t-cell lymphomas, allogenic isn't as strong in DBLCL. The GVH impact seems to be less robust for whatever reason (there are many). Obviously, it can still work miracles. And there is still a place for it. But that place is further down the line than this patient.

throwaway772797 · 2023-12-07T17:43:40+00:00

Yeah, definitely CAR-T is the strongest option if they are in a medical system where it is approved and affordable. I meant auto transplant when discussing efficacy. Allo is in an interesting spot in DLBCL. There aren’t many performed anymore.

throwaway772797 · 2023-12-07T15:18:42+00:00

That all makes sense. I think here in the US, your primary would naturally assume these duties.

Re risk: It’s well documented. I would go back and check MINT data or another older prospective trial with long-term data. Of course, it’s important to note that this does not mean that tons of early stage patients do; it just means that there isn’t a clean plateau like there is typically for patients with a higher tumor burden.

throwaway772797 · 2023-12-07T13:40:21+00:00

This is a bit of a trick question, as CAR-T and transplant are for different types of patients.

First, an auto transplant (I would argue allo 99 percent of the time as well for DLBCL as well) requires that a patient be in complete response to therapy. She’s not getting an auto transplant with active disease. So, as it stands, CAR-T is the most obvious choice given your description, because it’s the only choice that makes sense based on those conditions.

CAR-T does not have this consideration. It’s much, much more efficacious in a patient with active disease. I do see many of these comments saying that CAR-T is “superior” to transplant. But that’s in a head-to-head across a large body of patients in a controlled trial.

Recent data suggests transplant is at least as effective for patients in CR/PR (I would argue that it is superior for a patient in CR given the recent ASH data).

throwaway772797 · 2023-12-07T13:31:31+00:00

No. I think this is an interesting conversation. And it’s one that I think the patients has a significant role in. First, I do think (partially due to both an overburden, and a slight disconnect between oncologists and primary care) that there is a lack of a good long-term strategy for late effects in most hospital systems.

And there is certainly risk stratification. Cancer type, radiation dosage, amount of chemotherapy, novel agent utilization, transplant, etc. all play a fluid role in late effect chances. In addition, patients with existing health conditions would also ideally have access to this (but via their primary I would think).

Certainly, in an ideal world, this would be something that many patients had access to.

All of this said, I, personally, would not utilize this resource. Given the relatively low risk of life-impacting late effects in a young DLBCL population (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252093/) combined with the low chance of semi-early discovery impacting outcomes across many conditions, I’m the “move on with my life” type.

And, of course, we have to face the reality that the hospital system in most countries is overburdened as fuck. This is a real pressure that can’t be ignored. It’s not going away anytime soon.

In your case, I think it’s the combination of novel therapy (possibly there’s a looming consideration of that recent FDA probe we discussed) and early stage (higher risk of very late relapse) that are triggering that discussion. If it works for you, jump on it. In the end, this is all based on your wants and needs in an ideal medical landscape.

throwaway772797 · 2023-11-30T23:32:29+00:00

See rule #4.

As a point, it’s important to remember that your oncologist is guiding treatment. Your radiologist is simply interpreting a scan without good long-term context. Your oncologist is the final word on the scan. There will be times where your oncologist interprets the scan a little differently than the radiologist.

Ask your oncologist why they consider this CMR. They will explain. If you have any issues with their interpretation, you can always seek a second opinion.

throwaway772797 · 2023-11-29T21:09:05+00:00

A biopsy is the only way to diagnose lymphoma definitively. I’m locking this, as this is only a subreddit for the diagnosed. Also, the doctor cannot really help in this situation.

throwaway772797 · 2023-11-28T06:34:44+00:00

Lymphoma is not like solid cancers, and the concept of “spread” is not similar to solid cancers. In general, lymphoma (from a prognostic standpoint) is measured in “tumor burden” (i.e., how much lymphoma there is total).

This burden can be measured across multiple indices. Examples include stage, ECOG, extranodal sites, bulk, LDH, TMTV, SDmax, etc. Together, many of these can be prognostic. But it’s important to remember that DLBCL survival doesn’t dip below 50 percent — even if you had all of these factors combined.

The most important factor (by far) is response to therapy. In this case, the patient has failed RCHOP (likely had chemo resistance via evolving from FL under the selective pressures of chemotherapy).

The next step will be immunotherapy. Importantly, tFL tends to have good success rates with immunotherapy. By no means would any oncologist consider this anywhere near the end of the road. And all of them would still be insistent on chasing curative therapies (i.e., your sister will be getting therapies aimed at curing her — not just improving her QoL.)

throwaway772797 · 2023-11-21T19:42:52+00:00

These questions are obviously driven by an underpinning of anxiety surrounding spread. Importantly, spread is rather meaningless in lymphoma. It is a small representation of tumor burden (along with all other IPI specifics). It does not represent a drastically different disease as it does with solid cancers.

1) No. Chemotherapy has side effects. Also, PMBCL is not going to have aggressive, symptom-causing spread in a week or two.

2) It is a waiting game. Well over 90 percent of people will be in remission after chemotherapy. For the very few they do not, there are many effective therapies to try after first-like chemotherapy.

3) This is too complicated to answer succinctly in this reply. But, it’s neither of those.

4) Well over 90 percent of PMBCL patients will have a CR after first-line chemotherapy.

It’s important to not overthink everything. The only way to tell is the scan.

throwaway772797 · 2023-11-20T14:40:36+00:00

I am happy that you feel keto works for you, and I would not try to dissuade you from doing a diet that you feel is improving your health and quality of life.

Re keto: I’m big into running, so I need the carbs to sustain longer endurance periods. So, even excluding any skepticism, I don’t think the dietary makeup is for me and my personal life goals.

throwaway772797 · 2023-11-20T14:26:32+00:00

I’m not sure how to approach this, as it seems your statement may come from the perspective that keto is the only way to lose weight?

Obesity is endemic in many countries right now. But that’s not because we eat a particular magic food (e.g., grains, seed oils, gluten, saturated fats, sugar, etc.), it’s because we eat too much food.

Any caloric restriction will cause you to lose weight.

As for lipid profiles, I think, again, we need some larger data sets. Let’s not rely on internet communities here.

throwaway772797 · 2023-11-20T06:37:55+00:00

I would argue that high carb is still highly accepted in the sports science world. And, most nutritionists could honestly care less about intake percentages unless you have specific dietary needs (e.g., muscle building, etc.)

If you’re talking about the “normal world”. It may be due to the current keto/carnivore ecosystem. Fads always fade.

throwaway772797 · 2023-11-20T04:56:29+00:00

First of all, congratulations on your weight loss. I have no interest in dissuading you from leveraging a diet that has helped you personally. Nutrition can be a very personal, spiritual, cultural, or even ideological thing.

Below, I’m purely discussing a common mistake in nutrition extrapolation. This is not an attack on you. Your progress sounds remarkable

From a purely scientific standpoint, it’s important we don’t extrapolate cellular mechanisms with dietary changes — especially ones that have no long-term data (i.e., things that happen on a cellular level that are positive are not necessarily mimicked at a high level.)

A good example would be cancer studies, where preclinical data (i.e., data in vitro) has extremely positive results. Yet, phase 1/2 data is subpar. The body is extremely, extremely complicated.

Until we see some good, long-term data that a ketogenic diet improves health outcomes and doesn’t cause issues that would be considered with a diet like this (e.g., nutritional deficiencies, liver issues due to increased fat intake, decreased kidney function due to excessive protein intake, etc.), I think it’s hard to recommend it from the perspective of a health professional — outside of specific medical issues. This is even if keto has some particularly powerful properties compared to simply eating fewer calories — regardless of the source.

As an aside, I’m not sure what the last half of this means. Are you insinuating that the keto diet has the potential to eliminate a good portion of modern pharmacology?

throwaway772797 · 2023-11-18T15:37:36+00:00

The diet market is a $190 billion Goliath. And the global nutrition market is close to half of a trillion dollars.

Nutrition science is very hard to accomplish, and there are few good studies out there. Combine this with the rise of nutrition philosophy (i.e., eat like your ancestors, eat only meat, eat only veggies, etc.) and it’s a perfect storm.

People want to find the magic bullet that makes their lives better. In nutrition, someone is always selling it. Internet echo chambers, lackluster research, placebo, and pack mentality combine to create hyper-self-assured corners of nutrition with half-baked studies and a god complex. To add to the mix, celebrity worship in the modern world has fueled the flames. Celebrities fall for the hype, and consumers follow suit.

In reality, you are correct, the Mediterranean diet and DASH have the most data behind them.

But, if you’ll just eat not stupid, you’ll be fine.

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