8 replies to this topic

[jmoorhou]

www.sfgate.com/news/article/Novel-cancer-treatment-wins-endorsement-of-FDA-11284491

[r06ue1]

Nice story.  

 

But some bad news:  

 

One of the big issues in CAR-T cell therapy - the cost, which analysts say could be in the hundreds of thousands of dollars - wasn't discussed because that is beyond the FDA's purview. Novartis hasn't released pricing information.

 

I'm guessing that this will probably go up in cost rather than down, just like our medications, especially if it is a lifelong cure.  

[kat73]

I'm pretty sure CAR-T treatment, as of now, is not something for us anyway.  It works on the B white cell line and that isn't where our problem is.

 

Correct me if I'm wrong, Trey?

 

As for price, things would have to change a lot before this approach would be deemed cost effective by insurance companies, I think.  It would have to constitute a cure.  Otherwise, why would something with such dramatic, dangerous, and costly side effects be a first-line therapy when TKI's are so effective and with milder side effects?  Maybe for salvage purposes?

[Trey]

I have only seen CAR-T success stories regarding lymphoid leukemias (ALL and CLL).  CML is a myeloid leukemia.

[missjoy]

 

Front Immunol. 2013 Dec 31;4:496. doi: 10.3389/fimmu.2013.00496.

 

Dendritic cell-based immunotherapy for myeloid leukemias

 

Schürch CM1, Riether C2, Ochsenbein AF3.

Abstract
Acute and chronic myeloid leukemia (AML, CML) are hematologic malignancies arising from oncogene-transformed hematopoietic stem/progenitor cells known as leukemia stem cells (LSCs). LSCs are selectively resistant to various forms of therapy including irradiation or cytotoxic drugs. The introduction of tyrosine kinase inhibitors has dramatically improved disease outcome in patients with CML. For AML, however, prognosis is still quite dismal. Standard treatments have been established more than 20 years ago with only limited advances ever since. Durable remission is achieved in less than 30% of patients. Minimal residual disease (MRD), reflected by the persistence of LSCs below the detection limit by conventional methods, causes a high rate of disease relapses. Therefore, the ultimate goal in the treatment of myeloid leukemia must be the eradication of LSCs. Active immunotherapy, aiming at the generation of leukemia-specific cytotoxic T cells (CTLs), may represent a powerful approach to target LSCs in the MRD situation. To fully activate CTLs, leukemia antigens have to be successfully captured, processed, and presented by mature dendritic cells (DCs). Myeloid progenitors are a prominent source of DCs under homeostatic conditions, and it is now well established that LSCs and leukemic blasts can give rise to "malignant" DCs. These leukemia-derived DCs can express leukemia antigens and may either induce anti-leukemic T cell responses or favor tolerance to the leukemia, depending on co-stimulatory or -inhibitory molecules and cytokines. This review will concentrate on the role of DCs in myeloid leukemia immunotherapy with a special focus on their generation, application, and function and how they could be improved in order to generate highly effective and specific anti-leukemic CTL responses. In addition, we discuss how DC-based immunotherapy may be successfully integrated into current treatment strategies to promote remission and potentially cure myeloid leukemias

[Trey]

Dendritic cell-based immunotherapy is not CAR-T immunotherapy.  Dendritic immunotherapy for CML patients has not been very impressive, and is more of a "vaccine" approach and has been mainly used after bone marrow transplant to boost the immune system. 

[jmoorhou]

Sorry everybody, I saw this and got excited, article just said Leukemia...

[r06ue1]

There really isn't too much activity going on for CML and immunotherapy, probably due to the fact that we can live a pretty normal life if we take our TKI's.  The only CML immunotherapies I've heard of were related to transplants.  

 

For AML (which has about a dozen sub-types unlike CML), they are looking at immunotherapy and reprogrammed T-cells are one part of that.  

 

New approaches for the immunotherapy of Acute Myeloid Leukemia

https://www.ncbi.nlm...les/PMC4628787/

[Trey]

The problem with making immunotherapy work for CML is that CML begins very high in the hematopoietic (blood making) hierarchy, higher than any other form of leukemia.  The lymphoid leukemias (ALL and CLL) start much lower in the hematopoietic hierarchy, so can be more easily targeted by things like CAR-T.  The higher the cells are in the hierarchy, the more alternate survival mechanisms they have.  This is why one treatment approach does not apply to all forms of leukemia, and the separation of efficacy is most likely when divided by myeloid and lymphoid forms.

 

Here is a great paper on the genetics of CML.  Of course, it was written by me:

http://treyscml.blog...ics-on-cml.html