Tuesday, July 21, 2009

Quarterly Teleconference: Update on Immunotherapy of Melanoma

The Melanoma Research Foundation sponsors a quarterly teleconference that brings together advocacy groups, survivors and family member and friends. The guest speaker on this teleconference is Jedd Wolchok, M.D., Ph.D an Assistant Attending Physician at Memorial Sloan-Kettering Cancer Center. Dr. Wolchok's expertise is in the treatment of metastatic melanoma.

You can get more information or download the audio recording of the teleconference from the Melanoma Research Foundation's Website.

I've also provided a summary of the teleconference below. This was to help me ensure that I had an understanding of what was talked about. I decided to share for those who are interested.

The immune system has a role in the treatment of melanoma. Documented cases of "spontaneous remissions" have occurred. They are usually cases of melanoma. This happens when the immune system learns something and can begin to recognize the tumor. There is proof that a cell called a Macrophage can recognize tumors. Immunotherapies are designed based on the idea that the immune system can in fact fight off melanoma cells.

Active immunotherapies like vaccination train the immune system to recognize and target melanoma cells. These drugs are injected with a sole purpose of training the immune system what to look for.

Passive immunotherapies like interferon and interleuken-2 are generalized treatments that merely activate the immune system. In cases with interferon, studies have seen that patients who develop auto immunity were most likely to benefit from the treatment. Auto immunity is a state where your immune system is without prejudice attacking normal cells.

Cancer vaccines are not typically given to those with fast growing advanced melanomas. It takes time for the immune system to build antibodies as a result of the vaccine. In advanced cases, time is a precious resource that must be used wisely. Though some regression has been seen, there are currently no vaccines have been proven to show a prevention of recurrence or long term durability.

The immune system has built in checks and balances that prevent it from attacking normal cells. Since melanoma cells look very similar to melanocytes, it is difficult to get the immune system to recognize the bad cells. Potency of a particular vaccine would be the difference of finding a working dose versus putting the body into auto immunity. Some vaccine trials are seeing negative results where some people receiving the placebo are doing doing better than those receiving the vaccine.

IL-2 is the only FDA approved immunotherapy agent for Stage IV Malignant Melanoma. The other approved treatment is a chemotherapy drug called Dacarbazine. IL-2 was approved nearly 11 years ago based on studies that showed that a small number of patients had long term remissions (over 10 years). IL-2 doesn't attack the tumor, instead it activates the immune system in an attempt to fight off the disease.

There are severe side effects experienced with IL-2 and it is difficult to tolerate. It requires a highly experienced staff to identify and treat the side effects. In addition, a very low success rate of about 5% is seen for this type of treatment. For those small few, the benefits are huge!

Experimental therapies for metastatic melanoma include targeted agents such as one called anti-CTLA4. There is a protein on the T-cell called CTLA4. This protein acts like a brake and prevents the T-cell from becoming over active. Over activation can lead to cell death or auto immunity. A drug Ipilimumab (MDX-010) is an experimental drug that prevents the CTLA4 from suppressing the T-cell and allowing it to become more active with the hopes that it will be more aggressive against melanoma cells. Current studies are showing up to 15% of patients are receiving objective responses. An additional 15% are seeing stable disease. A person can live a long time with a so called "stable disease". Results from recent studies which could lead to FDA approval are still pending.

A similar drug called Tremelimumab did not have as much effect. Clinical trials have been cut short when in comparison to the already available chemo agent, patients did significantly worse.

Trials with immunotherapies are difficult to administer because unlike chemo where effects are seen right away, it take time for the body's immune system to activate and forge an attack. Tumor shrinkage can sometimes take months. Additionally, one may see tumor shrinkage after earlier scans show tumor progression. Results are therefore better recorded in survivability of patients versus objective response from tumors. How many people are living one year after treatment, etc.

Another experimental drug targets a protein call PD1 which is also found on the T cell. When activated will cause programmed death on the T cell. Melanoma cells express PD1 ligand which quickly kills the T cells and prevents the immune system from winning the war. The new drug prevent the activation of the PD1 protein in an attempt to keep the cell alive to continue fighting.

In conclusion, Dr Wolchok expressed that we have a lot of reason to believe that the immune system can play a role in treating melanoma. We have tools that prove that it can cause regression. Next steps are to find the right combination of treatments to setup a multi pronged attack against this disease. We must impair the pathways and prevent melanoma cell division.

Dr Wolchok then continues for another 30 minutes answering questions from those who attended the teleconference.

1 comment:

maphere said...

Hi Mike,

Have you considered Ipilimumab?

In regards to timing of IL-2 I recommend you read this guys blog:


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