Anyone had CAR-T therapy for solid tumors? (pancreatic cancer)

Hi - I am 75 and had CAR-T therapy last February. I had persistent Diffuse Large B Cell Lymphoma. Ie it was not responding to chemo. 30 days later I was clear - Magical!

I had CAR-T therapy last February for DLBCL. It was persistent in my duodenum and had spread to my pancreas and liver. 30 days later I was clear - Magic! I am headed for a 1 year PET mid February.

@indyellen, I pulled your comment into its own discussion so that it could be posted simultaneously in the CAR-T Cell Therapy group and the Pancreatic Cancer group. I hope you also saw the helpful reply from @kirkwilliams2049.

Ellen, that is great news that you are a probable candidate for a clinical trial of CAR-T cell therapy for pancreatic cancer. When do you find out if you will be on the trial?

Hi @indyellen ,

I finally saw your post after Colleen copied it to the pancreatic cancer group. I'm really interested in your situation, but have more questions than answers at this point.

My understanding is that solid tumors (like pancreatic) have been really difficult to treat with CAR-T cells, so if you've got access to a new trial, it might be something really groundbreaking.

My trial last year (not successful) used CAR-NK (Natural Killer) cells as an alternative. It was a FIH (First in human) trial that required a 3-week stay in the SCT (Stem Cell Transplant) ward of the hospital, where most patients were getting CAR-T cells for other types of cancer. It was kind of funny that the researchers and staff had so much experience with T cells that they kept referring to my treatment that way and then correcting themselves a second later.

I'm really interested in anything else you're willing to share about this trial.

Best of luck with it!

--mm

I am in Edmonton Alberta Canada so this is probably not applicable depending on where you are located. My understanding is that modified T cells look for the CD19 marker on offending/mutated B cells. Both variations (Standard of Care and locally modified) look for this marker. Bear in mind that I am a patient not an expert.

There was a study done about 2.5 years ago that indicated that if your B cells are histiocyte rich, that CAR-T had no effect. The study group was only 9 patients so it is far from a statistically significant group. I can’t locate the study right off but it was reported by the National Institute of Health. Again I am not an expert but this may give you some talking points to discuss with your team.

Hope things work out for you. I am pleased to answer any other questions you may have.

I haven't tried a CAR-T trial for my solid tumor (endometrial), but when I went to a clinical trial doctor to join a small molecule inhibitor trial, they tried to sell me on a CAR-T trial. I said something along the lines of "absolutely no way," and that as far as I knew, no CAR-T had ever worked on a solid tumor (see below). They didn't contradict that statement, but then persisted in trying to get me to let them test my biopsy specimen for the antigen targeted by the CAR-T. I said OK to that. My specimen was positive, making me eligible for the trial.

A couple months later, when I was having safety issues on the small molecule trial, the doctor brought up the CAR-T again as a possible next move. Shortly thereafter a patient died on the CAR-T trial (presumably not at my location), and the trial was terminated. Remarkably, last week when I failed on the small molecule trial, the doctor brought up the CAR-T again, saying they were going to start a trial on a new, improved version.

So the question is, why are they trying so hard after I said "no"? (They haven't forgotten.) I actually really like this doctor and hate to say this, but my thoughts go to money. Clinical trials bring in money to doctors and institutions for paying staff, keeping the lights on, etc. (ie 'indirect costs"). To put it crudely, guinea pig recruitment is part of their business model. Prestige my be part of the equation as well. Maybe I'm excessively cynical, but it is worth keeping in mind that there are potential conflicts of interest in this business. I was very clear about my position on CAR-Ts, but they really, really wanted to test my specimen anyway. It had to be because they were getting paid.

Before writing this post, I went looking for reports of CAR-Ts that had worked in solid tumors, and found that there have been a couple, sort of. I read a review in Nature Reviews Clinical Oncology from 2023 entitled "CAR T therapy for patients with solid tumors: key lessons to learn and unlearn". It's paywalled, but I have a PDF, and could send it to anyone interested. It's not an easy read, but you can probably get the gist. It's mostly about why CAR-Ts don't work on solid tumors. But it mentioned two trials that were promising, one on gastrointestinal cancers (Qi, C et al. Nat. Med. 28. 1189-1198 (2022)) and one on pediatric neuroblastoma (Del Buffalo, F et al. N. Engl. J. Med 388, 1284-1295 (2023)). This review is over a year old, so there may have been more "success" stories since then.

But my view on CAR-T trials for solid tumors is still that it is extremely unlikely that the patient will benefit. You're mostly contributing to science.

I relapsed over a year ago. A spot on my duodenum resisted chemotherapy. I am not sure if my team even knew that the node was solid or not. They gave me 40% odds of a CAR-T clear, 30 days later I was clear with minimal side effects. In my view, life is about probabilities. And they are not always in your favour. I felt it was worth a shot. And retrospectively, it was.

Best of luck with whichever path you choose. Just stay positive.

Leukemias and lymphomas, like DLBCL, are hematological malignancies and are not considered "solid tumors" even if they do form a discrete tumor. B-cell cancers like DLBCL, as well as multiple myeloma, have been where CAR-Ts have repeatedly shown success.

In contrast, CAR-T trials on solid tumors like lung, pancreatic, colorectal, etc. have almost universally failed. It's comparing apples and golf balls.

CD19 is a protein that is found exclusively on the surface of B-lymphocytes (aka B-cells) and B-cell malignancies. It is the target of the CAR-Ts used to treat B-cell malignancies.

The goal in designing CAR-Ts is to identify a protein found only on the surface of certain cancer cells, but no normal cells, and have the CAR-T target that. For B-cell malignancies that is CD19. For other cancer types it is different proteins. The CAR-T for treating a pancreatic cancer would target a different protein.

We fly to Seattle tomorrow for a few weeks’ evaluations before I know if I’m approved for the trial. Cell collection day is set for Feb 10.