I am currently thousands of miles from home, staying in an apartment with my wife about an 8 minute drive from MD Anderson. We came to MDA to take part in the CAR-NK trial but restaging showed that I am not a good candidate. Both the CAR-NK PI and a CLL specialist recommended CAR-T.
Here are three CAR-T trials that are available both at MDA and nearer to home:
Precision BioSciences (MDA, Stanford)
JCAR017 (MDA, UCSF)
KTE-X19 (MDA, Stanford)
The Precision BioSciences trial is allogeneic CAR-T. That means I wouldn’t have to wait for my own T cells to be engineered and I wouldn’t need lots of healthy T cells. I don’t think CAR-T trials screen for T cell health so I wouldn’t know the health of my T cells before signing up. Because the T cells are not my own I think they use heavy immunosuppressive drugs. Based on that, and past hospital stays for infections, I am wary of allogeneic CAR-T.
Anyone considering CAR-T has to at least take a look at JCAR017. It is the largest (?) CLL CAR-T trial. There is an option to be on this trial with and without ibrutinib. The off-target effects of ibrutinib may lower the risk of CRS and neurotoxicity and improve the health of your T cells prior to harvesting. I am very scared of CRS and neurotoxicity and so cling to the hope that ibrutinib would help.
I don’t know anything yet about the Kite trial other than it did a good job for those with MCL.
I read that high disease burden (makes sense) and low platelet count (no idea why) are risk factors for CRS. I have both.
MDA is concurrently running many CLL CAR-T trials that are recruiting so I assume there is a lot of knowledge shared across many people of how to detect (early) and treat CRS and neurotoxicity. Stanford is running 2 such trials and UCSF one.
I am seeking help: (1) which trial to choose, (2) how much does it matter which institution you choose in a multicenter trial, (3) what questions should I ask the trial principal investigators, (4) what is like to be a CAR-T patient.
The photo was taken by my wife while I was at MD Anderson.
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john-doe
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Go to the Car T page. Lots of info plus you can read Dr. Koffman’s blog about his car t journey.
My husband was treated at MD Anderson (not for CLL but for aplastic anemia). Every other doctor including NIH told him nicely to go home and prepare to die since he didn’t respond to any treatment and was considered too old (over 70) for further treatment. At MDA they agreed to treat him, he had an unrelated donor stem cell and five years later he is a pretty healthy 76 year old. So I have no experience at MDA for CAR T but it is an amazing place.
Please direct message me if you need any info about housing and other support services that you might need in Houston.
He’s a very good CLL communicator. I had only heard him interview others, never as the interviewee.
Wow, it was difficult for me to hear about the side effects he had on CAR-T. Through pioneers like him I think (hope) much has been learned in managing side effects.
If you are willing to be out of state, have you looked at Fred Hutchinson? Not only is Washington state still masking/taking precautions, my understanding is they have on-site suites/apartments for patients. Unlike regular hotels or housing, they were at least clean room if not positive pressure HEPA filtration. I looked at them years ago when considering a BMT. Things may have changed since then.
And re: the JCAR trial, from what I am reading in the database it's the SLL patients that get the ibrutinib, not the CLL ones. It's stated in the Brief Summary of the Study Description. If receiving it was important to you.
If your hemolytic anemia is still active, I understand its an exclusion for the PBCAR20A. Of course, the info in clinicaltrials.gov may not be correct, as inclusions & exclusions for a trial are modified.
I think there are clear data that adding ibrutinib improves outcomes in CAR-T patients so that being including in any protocol would be critical for me and more so for you if you have a significant disease burden. The new Kite drug looks promising but the data is less mature. I would not be keen on an allogeneic CAR-T. Full disclosure: I am doing great 3 years post JCAR-014 at the Hutch. Stay strong, Brian, CLLSociety.org
Hi - you can see from the relatively low number of responses that Car-T is still a relatively new field in CLL and for most of us..
However, I really think that Brian and the CLL society’s webpage are probably the beat source of i formation for you.
I watched some very encouraging Car-T cells webinars orchestrated by Brian and with the best specialists in this field, who gave much confidence that progress is being made, and hope that one day, Car-T might really work for most CLL patients. I am sure you’ll find the recordings an Brian’s webpage.
And I guess tou have seen by now, CLL Society is organizing the next Car-T cell webinar on April 21st...stay tuned.
I was given a choice of the JCAR-T or the LOXO 305 study at MDA. I chose the later and am in remission 9 months later. I personally would ask any institution you are considering how much experience they have with your choice and what their outcomes have been. Experience is a great teacher. Recognizing side effects and managing them appropriately is paramount. My impression was that MDA had a lot of experience but I did not do any comparisons. I agree the thought of CAR-T was daunting for me and I certainly understand. Best of luck to you. Tony
Hi JD, Can you please elaborate what it was about staging that disqualified you from the CAR NK trial?
As far as the cytokine storm and neurotoxicity side effects of CAR-T, I would ask them pointedly about how well they can help you manage these should they occur and what their track record has been in this regard. I have heard that these side effects either don’t occur or are less likely to occur with NK CAR; however, even with CAR T, the occurrence can depend on the target. I have posted about the work done by Dr. Sewell’s team at The Univ. of Cardiff using CART-T targeting MR1 which supposedly is specific to cancer and therefore could be used against a wide variety of cancers. Phase 1 trials start later this year. In context, this target (MR1) supposedly does not produce these two side effects. So among the CAR-T choices you now have, do they all target CD19? If any of them have a different target, I would ask what do the data collected thus far say both with regards to efficacy and the incidence of these side effects.
And finally I have read about one of the earliest CD19 CAR-T trials that involved three patients for whom that was the remaining treatment option. Two of the three went into a complete remission and I believe 8 years later and counting, they remain so. The third patient did not have a complete remission but subsequently had a manageable disease again. And they all experienced the two notable side effects. So if you are confident in the answers regards side effect management, there remains a lot of promise in what this treatment has to offer.
Your CLL community will be thinking of you! Please keep us posted.
I wasn’t a good candidate for CAR-NK because I had too much marrow involvement as detailed here: healthunlocked.com/cllsuppo...
The Precision BioSciences allogeneic CAR-T targets CD20. The other two target CD19. Interesting that side effects depend on the target. Thanks for that nugget.
1.5 years out Brian Koffman said he had no B cells. Would be neat if they could target something that is only on CLL cells
Thx for the link. I will read it shortly. It would be interesting to see if CD20 versus CD19 influences the probability of experiencing the notable side effects. Please let us know what you learn in that regard. Of course this has to be weighed against efficacy. And yes, it’s that kind of specificity it is believed MR1 will offer because it’s a target that is supposedly specific to malignant cells including, but not limited to, CLL. I seriously hope it’s true! I have posted that I will get a Welsh Corgi if it is and I would do so even if I never were to require the treatment - it would be a breakthrough worth celebrating for all that would benefit.
Hi JD, I don’t know how far along you are in selecting a CAR-T but another thought I had: is there any greater prevalence of CD19 or CD20 expression? I would think if there were, going for the most prevalent would be a consideration.
So it seems to me you now have another question to ask: “How robust are my T-cells?” I don’t know how they evaluate that. You can look at the CD4/CD8 ratio for starters but there are people who will forget more than I will ever know. But someone with that insight is, I should think, who you would like to talk to. Seems to me the answer here is really the key to success of this therapy. They are not there yet with the allogenic option pending progress on CRISPR engineering but they will be in time. So in the here and now, maybe the follow up question is: “Well given the current state of my T cells, what realistically would “success” of this therapy look like?” If it can buy you significant time, I believe there is going to be a race to perfect this technique, especially if MR1 is truly a cancer specific target - that is such a big piece of the puzzle. And we should have an answer to that within a year.
I can't recommend a trial for you based on your specific needs and everyone's reaction to CAR T is different, but I can tell you about my experience with JCAR017. In June 2019, I was enrolled in the TRANSCEND CLL 004 trial
This is a multi center trial and may be available for you closer to home. I was fortunate enough to live near a participating center so I did not have to relocate. If travel is necessary, the Leukemia & Lymphoma Society offers travel assistance
I was assigned to the ibrutinib arm of the trial, even though I had previously become refractory to ibrutinib. After leukapheresis, it took nearly a month to prepare the CAR T cells, but that seemed to be a function of when your cells get there in the processing cycle. The modified cells were given on an outpatient basis and I went home. CRS symptoms (fever) appeared five days later and I spent the next six days in the hospital, miserable but tolerable. Other than hand tremors, there were no neuorotoxic effects. By day eleven post infusion, a bone marrow biopsy showed no sign of CLL. Full recovery took less than two months and there is still no evidence of CLL.
As presented at ASH in 2020, the overall JCAR017 results look encouraging, especially with ibrutinib, although I don't know if ibrutinib has become the standard in the ongoing trial
I understand your concern about CRS and neurotoxicity and one of the reasons I chose the JCAR017 trial is that it seemed to have fewer severe side effects. Also, the doctors are becoming more skilled at managing the side effects and even in severe cases, they seem to be reversible.
To address some of your other questions, I don't think it matters which center you choose as the requirements of the trial are stringent and only institutions with the ability to manage the process should be involved, although it would be good to ask how many patients they have treated on this trial and what the outcomes have been. You should also ask about the followup testing involved. In addition to many blood samples, my study required five bone marrow biopsies and eleven CT or CT/PET scans. You should investigate your out of pocket costs. Although the trial pays for the CAR T cells, you may have to pay any hospitalization costs. Another factor is whether you can wait for the manufacturing of the CAR T cells. Some trials allow for bridging therapy. Finally, recognize that CAR T kills all your B cells, damaging your immune system (can't make antibodies). Do they come back? Maybe. Mine are starting to, but nobody can tell you because the process is so new. I've been told get the Covid vaccine, but it probably won't help you so act like you didn't.
I hope this has been helpful. Good luck in your journey. I have no regrets about mine.
It was interesting to see that two groups with different CAR-T doses were presented at ASH 2020. I had assumed they had already determined dosing.
Do they send people home after the JCAR017 infusion and then have them return if they are experiencing side effects. Or do they tend to keep people in the hospital for observation?
I got the low dose, but I believe they’ve settled on the higher dose going forward. I was told that with some types of CAR T, they know there will be a reaction so they keep you for observation. For the JCAR017, they send you home, but you must stay within 60 minutes of the hospital.
MD is top shelf so is Fred Hutch, as is UCSD, as is Dana Farber, as is City of Hope, as is Mayo...etc etc, it’s hard to beat the comforts of home when u get ur “Get out of Jail” card. RE JCAR017 with & without Ibrutinib I believe the selection of which treatment u get is randomized, such that u will b selected 4 1 or the other. I am getting my juice tomorrow & would prefer the combo but am getting the mono therapy. Fortunately I was on Ibrutinib when I had apheresis so hopefully that will benefit my juice. Anyhow I wish u the best!
Hi! I am a PhD cancer immunologist and worked on CAR therapy for a few years at the Fred Hutch center in Seattle before becoming a Chinese medicine Dr. I’m happy to help if possible. Please send me a chat if you would like to talk more or if I can provide any helpful information!Thanks!
Currently am, or was, an immunologist? Looks like you are no longer in that field. And that your work is in Prostate Cancer, according to ResearchGate, not CLL. Are you a CLL patient?
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