Friday, December 18, 2020

ASH: Natural Killers and Follicular Lymphoma

One more from ASH.

But first, Targeted Oncology wrote up a recap of ASH a couple of days ago, and described the presentations that they thought were most significant.  They list a few under Lymphoma, and the ones that focus on Follicular Lymphoma are those that focus on CAR-T (the ZUMA-5 trial) and on Bispecifics (there are a few of them). I mention this because those are the the ones that I saw the most buzz about online during and after ASH. So it's nice to see that the things I heard are also the things other people heard. I like being right. (And it should probably be comforting to you to know I get things right.)

Now, back to the last "buzzy" presentation at ASH that looked at Follicular Lymphoma:

 "Results of a Phase 1 Trial of Gda-201, Nicotinamide-Expanded Allogeneic Natural Killer (NK) Cells in Patients with Refractory Non-Hodgkin Lymphoma (NHL) and Multiple Myeloma."

GDA-201 is a treatment that involves Natural Killer Cells. These are a type of immune cell found in our bodies. Unlike some other immune cells that attack an invader (like a bacteria or virus), Natural Killer Cells attack our own cells that have been infected with an invader. Viruses, for example, work by taking over a cell and then multiplying rapidly. A Natural Killer Cell recognizes that this infected cell is different from other normal, and kills it off.  

This makes a Natural Killer Cell a really interesting target for Immunotherapy. Our own immune systems don't kill off cancer cells because cancer cells are not "invaders" or outsiders. Instead, cancer cells are our own cells that haven't learned how to die the way they are supposed to. Most of our immune cells will look at our own cells and leave them alone. But a Natural Killer Cell is made to say, "Hmm, something's not right here." But even a Natural Killer Cell won't kill off a cancer cell. Still not different enough from regular cells to be concerned.

GDA-201 gets around that by using someone else's Natural Killer Cells. The donor cells are trained to recognize cancer cells (the way the NK cell would recognize a cell that had been taken over by a virus), and goes after them. GDA-201 isn't the only attempt out there to use Natural Killer Cells, but it's the one that, so far, has shown some success with blood cancer.

For this research, donor NK cells were manipulated and grown in a lab. The cancer patients in the study were then given a monoclonal antibody (like Rituxan) to kill off or weaken a lot of the cancer cells. Then the NK cells were put into the patient.

Results were very good. It's a phase 1 trial, so there weren't many patients -- 15 with lymphoma and 15 with multiple myeloma (another blood cancer). Of the lymphoma patients, 6 had Follicular Lymphoma.

The good news is, all 6 FL patients had a Complete Response. For the whole Lymphoma group, the median duration of response was almost 9 months.  One-year estimates of Progression-Free Survival was 66%, and Overall Survival was 82%. 

Side effects were manageable. There was some concern that something like Cytokine Release Syndrome, which is common in CAR-T and some other immunotherapies, might be an issue. But at least at the doses that they tested, there were not any unexpected side effects (though there were some, of course).

This is a phase 1 trial, with very few participants, so there's certainly no guarantee that those good results for FL patients will remain in later trials. But it does seem like the makers of GDA-201 are planning to move ahead, and we'll likely see more of this treatment in the future. I kind of have a good feeling about this. (And hey, I was right about the other stuff, wasn't I?) 

But seriously, the concept does make sense, and I do think we'll hear more about this one n the next few years.

So no big blockbusters at ASH this year, but a few small things that are worth being excited about. At this point, we know that even small progress is still good progress.


 


9 comments:

  1. Bob.

    Thank you for all the strict attention and details that you pour over on a daily bases. I have followed all you update since my diagnosis of FL in 5/2018. I am two years in remission for FL and heading into my third year of maintenance.

    Sadly, my wife was diagnosed with bile duct cancer this week. Is there website you can direct me to the addresses my wife diagnosis in the manner that you so wonderfully do Sir?

    Thank you and God bless you. John K.

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  2. John,
    I'm so sorry to hear about your wife's diagnosis. Having been through the experience once doesn't make it any easier the second time, I'm sure. I wish you both the best.
    I tried to find someone in my network of cancer advocates who works with bile duct cancer patients, but unfortunately I don't know of anyone. Seems like a fairly rare cancer.
    I can recommend a couple of resources, if you're looking to hear from another patient:
    The Cholangelocarcinoma Foundation looks very reputable, with affiliations with ASCO and some other cancer organizations. They have a couple of services that might be helpful. The first is a mentoring program, where they would match you up with another patient, someone who can answer your questions about the experience. They also maintain a discussion board, where you can ask questions and get answers from other patients. It seems very active. The website for the foundation is https://cholangiocarcinoma.org/, and you can find those resources under the "Patients" link.
    The other resource is the patient guide from the NCCN (an organization of cancer hospitals that I have linked to in the past). Their Patient Guide to Hepatobiliary Cancers covers liver, gall bladder, and bile duct cancers, but it should have the best advice from professionals that is available out there, in fairly easy-to-read language. You can find it at https://www.nccn.org/patients/guidelines/content/PDF/hepatobiliary-patient.pdf
    These two resources will give you different things. The NCCN guide is very reliable, but not interactive. The Foundation sources will let you hear from other patients, but use your best judgement about the advice they give -- check with the oncologist.
    I'll keep looking for patient advocates who might be able to recommend other resources.
    In the meantime, take care of yourself. I hope your wife gets some good news as she gets farther into the diagnosis and treatment part of things. Feel free to email me so I know how to get in touch with you if I find anything more (bobtalisker@gmail.com).
    Bob

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  3. Hi Bob, please excuse off topic comment here. I am wanting to know if you are working on a post on the vaccine and lymphoma. CDC recommendations say that the immunocompromised can take the jab but it may not work so well with us as we have diminished B cells. CDC also hedges their bets by saying that the vaccine has not been studied in the immunocompromised population. I found this piece that I thought would be of interest to you even though it is not lymphoma research it describes a bunch of studies on Rituxan and vaccine response and might be a good starting place.

    The effect of rituximab on humoral and cell mediated immunity and infection in the treatment of autoimmune diseases
    Nichola Cooper
    Donald M. Arnold
    First published: 11 March 2010
    https://doi.org/10.1111/j.1365-2141.2010.08076.x

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  4. You know, I'm really hesitant to write about the vaccine because there are so many unknowns. In all my time writing this blog, there have been many things that I've started to write about, but never posted, because I just didn't feel like I fully understood the subject, and I wouldn't ever want to steer people wrong. This is one of those things.
    If the CDC is hedging, it's because they don't have enough data to say anything definitively. I'm not sure I can add anything useful. I just don't think the research is there in previous publications, and there hasn't been any research on this vaccine in the immunocompromised that could offer any new data. So I'm just not sure that there's any research that can give me the kind of answer I'd like to get. I have found that there are some questions that I cannot find answers to (and that is frustratingly true of many questions related to Follicular Lymphoma). After almost 13 years, I've learned where it's worth putting my mental and emotional energy. For me, this is one of those unanswerable questions.
    All I can tell you is, when I saw my oncologist in September, he recommended I get it. My state will issue guidelines soon about who should get the vaccine in the next phase of distribution. I expect my cancer hospital will issue guidance as well. And I plan to get it as soon as I am able. I will probably continue to live carefully, even after getting the vaccine, until I get word that I can go back to a "normal" life, hopefully sometime in the summer, when I can travel again to see family, and give some people some large hugs.
    I wish I could give you answers. But that's the best that I can do.
    Bob

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  5. Hi John

    Sorry about your wife's diagnosis. You might find some useful information on Facebook in the Bile Duct Cancer - Support & Awareness group - you can join this closed community of 4300 members.

    Also the American Cancer Society has a bile duct cancer site at https://www.cancer.org/cancer/bile-duct-cancer.html

    William



    William

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  6. Hi Bob,
    With regards to the vaccine, I think it would be prudent if everyone would check with their oncologist. We are all different and at different stages of our fNHL. My onc said it would be ok for me to take the vaccine because it is not a live vaccine. I am almost 14 years in CR/NED, but I do receive monthly IVIG infusions due to my highly compromised immune system from Rituxan. I admire the fact that you haven't written a blog about it. This could have serious consequences for some of us, so the best advice, in my opinion, is to check with your oncologist.
    Thank you for everything you do Bob. Here is wishing you the very happiest of Holiday seasons.
    God Bless!
    Jacqueline

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  7. Jackie, Yes! No matter what I say, no matter what anyone reads, the best thing to do is talk to your oncologist. They know your situation best. And if you don't trust what they say, find a new oncologist, if you're able.
    Bob

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  8. I completely agree and would never suggest that someone substitute info they found on a blog (even one as good as yours) for the advice of their physician. Full disclosure, my oncologist said to get the vaccine and I was lucky enough to be in group 1a so I took the jab yesterday morning. No side effects so far save a sore arm. Here's hoping my B cells are responding even though I do not have as many of them as non NHL people.Keep up the great work Bob! and thanks for your candid response.

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  9. I know you weren't saying you shouldn't listen to docs. That was just a reminder from me (and Jackie). I like to remind people every now and then that I don't always have the answers, and their onc is their best choice. Flattering that anyone would think that I do. Glad you were able to get the vaccine. Stay safe.
    Bob

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