ASH 2012: Dr. Wierda and Practical Advice on CAR-T Trials
In part two and final part of my interview from ASH 2012 with Dr. Wierda from MD Anderson (please see part one first to get oriented) talks about some of the practical issues, upcoming trials, and possible role of CAR-T in conjunction with the new TKIs (tryosine kinase inhibitors).
In effect, Dr. Wierda is painting a picture where a small molecule such as ibrutinib or idelalisib or ABT-199 or AVL-292 or others in the pipeline is being used to reduce the amount of disease (cytoreduction) and then adding CAR-T therapy instead of the riskier allogeneic transplant to get rid of the nagging residual disease that seems to be left by all these drugs, and with that two step chemo-free process offering the real possibility of a cure for our CLL.
As he stated, this are still many active area of research. Here's some issues that are near and dear to me.
Why the small molecules seem to move so slowly at ridding the body of all traces of disease- maybe we are just not waiting long enough or maybe it doesn't matter? It doesn't seem to matter in many patients with CML treated with imatinib (Gleevec). Will it be the same with CLL?
Can CAR-T therapy replace allo-transplants and become a practical, affordable path to a cure? A one-two knock out punch?
What about the rare relapses in CAR-T therapy with the cancerous clonal evolving to express no CD-19 and thus are no longer targets for the the engineered T-cells?
What are the bridges to these new therapies while we are waiting for answers?
Let's here a surprisingly practical discussion with one of the doctors who is not only discussing but creating this new future.
Dr. Wierda had to run off after this segment, so there is no part 3.
But Drs. Furman and Wiestner still have important things to teach us from interviews at ASH 2012 that I will be posting soon.
In effect, Dr. Wierda is painting a picture where a small molecule such as ibrutinib or idelalisib or ABT-199 or AVL-292 or others in the pipeline is being used to reduce the amount of disease (cytoreduction) and then adding CAR-T therapy instead of the riskier allogeneic transplant to get rid of the nagging residual disease that seems to be left by all these drugs, and with that two step chemo-free process offering the real possibility of a cure for our CLL.
As he stated, this are still many active area of research. Here's some issues that are near and dear to me.
Why the small molecules seem to move so slowly at ridding the body of all traces of disease- maybe we are just not waiting long enough or maybe it doesn't matter? It doesn't seem to matter in many patients with CML treated with imatinib (Gleevec). Will it be the same with CLL?
Can CAR-T therapy replace allo-transplants and become a practical, affordable path to a cure? A one-two knock out punch?
What about the rare relapses in CAR-T therapy with the cancerous clonal evolving to express no CD-19 and thus are no longer targets for the the engineered T-cells?
What are the bridges to these new therapies while we are waiting for answers?
Let's here a surprisingly practical discussion with one of the doctors who is not only discussing but creating this new future.
Dr. Wierda had to run off after this segment, so there is no part 3.
But Drs. Furman and Wiestner still have important things to teach us from interviews at ASH 2012 that I will be posting soon.
Labels: ASH 2012, CAR-T, Cure, ibrutinib, Idelalisib, interviews, transplant, Video
posted by Brian Koffman at
12:00 PM
2 Comments:
Brian,
The cons of CART were well covered by your interview - good job. The loss of CD19 with CAR therapy suggests the shaving seen with Rituximab used against CD20. Since ROR1 is a cell surface receptor would this imply that we will see a similar shaving of ROR1 or is the structure of ROR1 different from CD20 & CD19 in a way that would make it less vulnerable to shaving?
Also, is there any data suggesting that these CARs are able to attack CLL cells in the marrow and node compartments? This could be an achilles heel if CAR penetration into CLL germinal center tissue is limited.
WWW
Brian,
Thanks so much for the leadership role you've taken in getting out the facts of CLL, it's management, and where we're going in the future.
Great interview. Keep up the great work, and if there's anyway I can help,................ Let me know. I'll do my best.
Leo
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