An exciting approach to refractory myeloma is the development of CAR-T cells to recognize and kill the malignant plasma cells which mutate and are responsible for recurrence. Chimeric Antigen Receptor - T cell therapy has now been used in hundreds of patients with recurrent leukemia (89% success) and chronic lymphoma (~50% success), and is on fast tract for FDA approval. Now a few top institutions are using it for refractory, heavily pretreated myeloma.
The process involves an apheresis of one's own T cells, then genetically modifying them using a HIV virus vector to recognize surface antigens, be it CD19, CD38, or C138. They are then reinfused back into the patient, following engraftment of stem cells after a second autologous transplant, or not.
After studying my own options for my refractory myeloma, I have chosen to participate in the UPenn CAR-T CD19 clinical trial. I just finished the procedure on Nov.18th, following my second ASCT. Having recovered from the side effects of the second transplant, the reinfusion of my own CAR-T cells 13 days after was asymptomatic. Now I have to wait for evidence of efficacy with frequent labs and f/u bone marrow biopsy. Two women have preceded me in this trial, both of which are apparently doing great. I am the first male, and the plan here is for monthly patients for the first year.
I am convinced that some type of immunotherapy is the key to the Holy Grail of MM research, dare I call it cure. The devil is in the details, of course, and we need more institutions to open up these trials, and more patients to take advantage of them. Stay tuned; data from these trials may be very promising, and available in 2015!
Best wishes to all fellow MM patients! Jan H. Stafl MD
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So the modified t-cells goal is to delete any residual MM cells that have the CD-19 antigen, right? Any idea what % of MM cells that represents? Is there a before/after analysis via flow or NGS that compares residual MM after the 2nd auto vs after the t-cell infusion? Good luck! -Jack A
Hello Jack. Thanks for your interest. There are no firm answers to your questions, as I was only the third person to get CAR-T CD19 cells for MM. This clinical trial is for high risk pts who recurred within a year for 1st ASCT. The theory is that since all lymphocytes carry the CD19 receptor, plasma cells still carry them, even if present technology cannot often detect them. On my bone marrow aspirate just before the 2nd ASCT, researchers were able to detect some of those receptors though.
We get frequent labs to see how the genetically modified T cells function. The purpose of the ASCT is to minimize the tumor burden; T cells are given after engraftment begins (day 13 in my case).
Hmmm. It would seem the "before/after" analysis I mentioned would be part of the measurement criteria necessary to determine if the treatment was beneficial.
As you know, recurrences after ASCT occur in less than half the time the second time around. Detailed testing for MRD is done and the function of the T cells is closely monitored. Revlimid will be added for maintenance after day 100 as usual. With ALL there have been 89% durable CR rates found! With CLL, about 50%. Hopefully MM will be between these. Other receptor CAR-T trials are already underway as well. I'm convinced that some type of immunotherapy will be the Holy Grail for MM.
Jan Stafl- I was diagnosed with multiple myeloma at the end of August and am getting ready for my stem cell transplant. Is your myeloma high risk or low risk and where/with what doctor did you undergo the T-cell (CAR) trial?
I was dx in July 2011 with stage 2, high risk KFLC MM. I had my first ASCT following induction therapy in 2/2012, with a recurrence just 10 mo. later. I tried most FDA approved meds, becoming refractory to all of them. Therefore, after undergoing 2 cycles of VD-PACE chemo, I enrolled in a pilot CAR-T clinical trial at UPenn. I had another ASCT followed by CAR-T cells 2 weeks later just last month. At this point, this is the only trial with CAR-T CD19 that I am aware of. I am very happy to have gone through this trial. It does not sound like you need (or qualify for) this innovative immunotherapy now, but it may be an option if you have a recurrence in the future. Best wishes! Jan
Thanks so much for responding. How are you feeling and how has this treatment affected you so far? I am curious because I am still undergoing my 16 week therapy leading up to my transplant but just found out last week that my system is not responding to the treatment anymore (Velcade). My cancer cell levels stabilized for a few weeks and did not significantly go up or down until this past week when my doctor called and let me know the numbers are up and we need to use a new medication. He said the next step will be to take pomalidomide. Have you had any experience with that? The problem for me is that my insurance company said they will not cover this new medication, so I am in a difficult position. I'd appreciate any help or advice. I hope you are doing better. Are you originally from the czech republic by the way?
Hello Tadeus, sorry I could not reply till now. You guessed right, I am from Prague, leaving as a 12 yo after Warsaw Pact invasion in 1968 with my parents.
My guess is you are Polish?
So I feel just fine, thanks. In your situation, CAR-T is not an option at this point. You are undergoing induction novel agent chemo, and need to get to <10% plasma cells on the bone marrow bx before ASCT. You are refractory to Velcade, but have you been on Revlimid with dex? That would be preferable to Pom for you, and likely to be approved.
You could look into clinicaltrials.gov. But you are still at the beginning of your MM journey, and have several other FDA approved options: Kyprolis, BiRD protocol, and Doxyl, among others. Seeking an opinion of a MM specialist is your right, and a wise move.
I am an OB/GYN MD, now on sabbatical, but I have researched this oncologic topic at length. Don't get discouraged. At this weeks ASH meeting in SF, many new options are being discussed. The life expectancy has more than doubled with MM in the last decade. Enjoy life to the fullest. The Now is all that is certain anyway. Hope this helps! Best wishes, Jan
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