18 replies to this topic

[missjoy]

"The bone marrow has a protective effect on CML stem cells, and enables them to evade eradication by existing drugs," said Arnon Nagler, MD, of the Sheba Medical Center in Israel, who will lead the new study. "Preclinical data have shown that BL-8040 efficiently synergizes with imatinib in vitro and in vivo, overcoming the protective effect of the bone marrow, and we therefore hope that the combination of these two drugs will override drug resistance and suppress residual disease."

[gerry]

Not a cure, they are hoping it will improve the response to Gleevec for those people who don't have a great response to Gleevec. Supressing residual disease indicates to me that once you stop taking BL-8040 the CML will return.

They are still in the early stages of testing. Not sure it has acutually been tried on people yet.

 

But on the positive side the scientists/docs continue to look for answers and a cure.

[Trey]

It is well known that it is hard to kill off the highest level leukemic stem cells, and that they hide in the bone marrow niche.  That is why the TKI drugs have not been considered a cure.  But there will be a cure for CML some day.  The drug you mention just isn't it.

[missjoy]

Hi Gerry and Trey,

That is disappointing. I thought leukemia stem cells are the root problem. If a drug can move leukemia stem cells out of their niche, they will be eliminated by the chemo or TKIs. They have done II phase clinical trials on AML.The result is encouraging. They are starting clinical trials on CML now as Gerry mentioned.Trey, what approach do you think is most promising?

[missjoy]

http://www.cancernet...cal-testing-cml

Does any one know more about this BL8040?

[rcase13]

My doctor keeps taking about PD-L1. I can find very little about it. Has anyone heard of this? I think it has something to do with boosting the immune system?

[missjoy]

http://www.discoverc...JfcAaApmJ8P8HAQ

I found this article about PD L1.

[scuba]

http://www.immunothe...6-2-S3-P210.pdf

[Tedsey]

I know people will come down on me, but I am resigned to believe there will not be a cure in my lifetime (assuming I live a normal one--isn't that something that I can chance to think this way!).  Big pharma is all about making money and medicine is all about curing the symptom and not the disease.  I think there will only be more therapies in the future and a lot of drugs.  If they keep us alive longer with a decent quality of life, then it is not an evil in itself, but not a way to a cure (unless by accident).  Cancers are very complicated.  It is a miracle that a therapy was developed that has kept CML from advancing in most people.  I am grateful and I am also hoping with all my heart for a cure.  However, I don't think there is enough focus or motivation in that direction except by us.  I would LOVE to be proven wrong and have you all throw it in my face!  It would feel wonderful.

[Trey]

TZ,

At least the pharmas did not require TKI drugs to be taken aborally.  Or even arboreally, for that matter.  Or both simultaneously.  Think on that one.

 

Got Words?

[scuba]

In response to Tedsey:

 

I think functional cure is possible - in the same sense of someone getting a vaccine for a foreign disease; there may be "vaccines" that are for your particular cancer that causes a proper immune response. This new area of immunotherapy is already generating breakthroughs and more are coming. The big pharma company's will give way to the new immunotherapy company's and new technologies just like typewriters gave way to word processors and horse and buggy gave way to cars. I believe where we go astray is the notion that one bad cancer cell inevitably leads to cancer. And that unless ALL cancer cells are eradicated, there is no cure. I don't believe that at all. Cancer cells are generated all of the time. And cancer cells try hard to evade the immune system by pumping out proteins to shut down the T-cell response to the cancer. Immnuotherapy is all about super charging the patients own immune system not to get tricked by the cancer. 

 

You will see this solved in your lifetime. 

[missjoy]

Our oncologist told us patients who remained in remission with TKI secession were functional cured.  Is that the case?

 

I can't wait for a cure for CML. I am concerned for young patients who face a life time on TKI. We all know leukemia stem cells are roots of the disease, so  I often search for LSC elimination. That is how I came cross that BL8040 compound. It does sound encouraging when I see words like "move stem cells to peripheral blood....suppress residual disease, doesn't it. Especially, when I read this BL8040 is low toxicity, with or without TKI put leukemia cells apostasy.

 

I heard John's Hopkins were/are doing phase II CML vaccine trials. The phase I trial results were encouraging.

 

I understand the concern about  conflicts of interest between patients ' cure and pharmaceuticals ' revenue.  Do you think if a cure is found in a research center that the center can find a way to raise funds to commercialize the cure?    

 

ASH report 2014 mentioned that there was no lack of approaches ready to try in clinical trials but there were a lack of participants to conduct trials.  I thought the clinical trials could take place abroad where TKI is not available for all patients. I googled and found some interesting articles about outsourcing clinical trials. There are some challenges but not impossible.

[scuba]

Additional references on immune therapy approaches (at functional cure) being tried:

 

http://www.cancerwor...pact Factor.pdf

 

https://ash.confex.c...Paper13067.html

 

I don't what has become of the 'vaccine' CMLVAX100. The results were probably inconclusive since there has been no mention of it beyond 2010. 

 

What we do know is that CML cells do produce unique proteins that offer targets for T-cells. There does seem to be promise in this approach. Time will tell.

[missjoy]

http://m.hopkinsmedi..._results/J05121


http://www.medicalne...cles/175397.php

This is the vaccine of John's Hopkins.

[Tedsey]

TZ,

At least the pharmas did not require TKI drugs to be taken aborally.  Or even arboreally, for that matter.  Or both simultaneously.  Think on that one.

 

Got Words?

And I am GRATEFUL for that! 

Will I ever live that word down?!?  It is a good one though, eh?

[Tedsey]

In response to Tedsey:

 

I think functional cure is possible - in the same sense of someone getting a vaccine for a foreign disease; there may be "vaccines" that are for your particular cancer that causes a proper immune response. This new area of immunotherapy is already generating breakthroughs and more are coming. The big pharma company's will give way to the new immunotherapy company's and new technologies just like typewriters gave way to word processors and horse and buggy gave way to cars. I believe where we go astray is the notion that one bad cancer cell inevitably leads to cancer. And that unless ALL cancer cells are eradicated, there is no cure. I don't believe that at all. Cancer cells are generated all of the time. And cancer cells try hard to evade the immune system by pumping out proteins to shut down the T-cell response to the cancer. Immnuotherapy is all about super charging the patients own immune system not to get tricked by the cancer. 

 

You will see this solved in your lifetime. 

Thanks as always for the hope!

[chriskuo]

There are ethical issues in outsourcing clinical trials, even more than in outsourcing manufacturing to third world countries.

India is often mentioned as a possibility, but care must be taken because the number of qualified doctors is limited and the pool of patients includes many who are uneducated and may not be able to understand and give informed consent.  If the trials are being conducted in the US, then it would seem that additional trials may be appropriate in other countries.  But if the US is not conducting clinical trials, you have to question why trials should be conducted in third world countries.

[scuba]

http://m.hopkinsmedi..._results/J05121


http://www.medicalne...cles/175397.php

This is the vaccine of John's Hopkins.

 

This is all good - the research is heading in the right direction. There is little doubt in my mind that the "solution" to Cancer lies in antigen identification and then vaccine development which causes an immune response. TKI's do a good job of killing cancer cells in order to make room for our normal blood so we can live; But without a memory immune response, the cancer can (and often does) come back when therapy is stopped. Why some patients are able to remain progression free (40%) after stopping TKI treatment is intriguing. Did the patient's body develop an immunity over time (bought by the TKI)? Did the CML simply go quiescent? We don't know. But an immune response does seem likely.

[missjoy]

Most CML patients on TKI are doing reasonably well, so there are not many patients available nor willing to participate in clinical trials of novel therapy. 50% of patients who are eligible for TKI secession choose not to. I completely understand their concerns about stopping TKI. 

 

There is a shortage of CML clinical trials participants in the US. That is the reality. To advance the science to find cure, the best way to find participants is looking elsewhere. If some countries have large populations, there must be relatively large numbers of CML patients. Not all CML patients in those countries can afford TKI . Even with today's TKI med,  some patients are still on Chemo therapy or stem cell transplant. If we could connect the two dots, we would all benefit from the cooperation.

 

It is true there are ethical issues to deal with. The study I read said the main problems are local malpractice and corruption. The laws in other countries are different, eg. patients consent is not required, but rather consent from clinical trial supervisors.  Here there are more restrictions on drug approval if the clinical trials are conducted abroad.

 

The study also showed, despite the obstacles, the trend of in outsourcing clinical trials increasing 15% per year.

 

I am sure there are qualified doctors in major metropolitan centers in other countries. You can see that research into CML  is truly international; many authors with last names on published articles for example are Chinese or Indian.

 

Above all, we should conduct clinical trials using the similar standards/protocols as in the US. By no means, should we take lives of developing countries less seriously.  

 

Strikes me as an opportunity as our world becomes more connected in time and knowledge.