At approximately six months post my CAR-T infusion I was re-staged with blood tests and a bone marrow biopsy.
Re-staging is a euphemism for seeing how much if any cancer is left.
I already reported the good news that my peripheral blood shows no CLL. In fact, no normal B cells by flow cytometry that can find one cancer cell in ten thousand.
Now I can share the same good news from my bone marrow biopsy- MRD undetectable by flow.
This is great news, the best news.
I was hoping SCCA/Hutch might also do next-gen sequencing to see if there is any CLL lurking below the detectable levels by flow as they did at my 1-month staging, but they said they don’t do that once patients are sent home.
My CAR-T cells were also undetectable by flow in both the blood and the marrow. PCR testing is more sensitive by at least one log and CAR-Ts were found in my peripheral blood just above the detection level. They didn’t do PCR on the marrow.
When I toured U Penn’s impressive CAR-T lab, I was reminded that they have a couple of patients 7 years out who have no disease and persistent CAR-Ts. And when I say a couple, I mean two.
At least with the U Penn product it does seem that there is a strong connection between CAR-T persistence and remaining in remission.
The situation may be different for the Kite and Novartis product, where the CAR-T frequently go missing. Perhaps CAR-T cells do their work, and then disappear, or maybe just hide until they are needed again. If there is no cancer to respond to, they are no longer needed.
Dr. Cameron Turtle from SCCA/Hutch was asked at the ERIC 2018 meeting in Barcelona about which he believed was more important:
- The height of the T cell expansion
- The length of persistence
He said while the data is early, he believes, at least with the product that I received, that it is the height of the expansion and I had a massive expansion so I am feeling pretty good.
He speculated that what might really matters is the area under the curve and that is good news for me.
Drive the cancer so deep that it ain’t never coming back.
This is all so new that the truth is that no one knows.
If the depth of the initial remission that determines the durability of the response, mine was a deep as you can go.
This is from Dr. Utkarsh H Acharya.
Here is my question:
Yesterday I was at U Penn with Drs. June, Levine and Fraietta at their lab where they have patients whose CART are still around 7 years out and when they don’t persist, the patients tend to relapse.
At SCCA/Hutch, I understand that long term persistence of CAR-Ts is not seen as often and is not so closely correlated with outcome. Is this correct? Any insights as to the difference?
“I don’t think there is enough long term follow up on our experience to conclusively say in my humble opinion. Longer CAR persistence obviously implies continual surveillance against any residual or recurrently originating clones; but ideally if diseased clones are completely eradicated, the hope would be that there would be no recurrence regardless of CAR T persistence. With that being said, we know CLL is tricky with relapse potential and obviously prefer that patients hold on to their CARs as long as possible (stipulating disease biology remains constant and maintains the antigenic target since antigenic escape is well recognized in a subset of recurrences) but the forthcoming years will be telling of how CAR persistence/lack thereof translates to overall outcomes”.
I am glad my CAR-Ts are still detectable. They are my friends.