Thoughts on Antibodies

I don't know whether it is the time of year or something floating in the air but I have received a ton of emails about our decision to go to Sloan lately. Seriously, over the last few weeks, I have received about 10 email asking me about our thoughts and experience on 3F8. This also comes at a time when two of our local families begin their first rounds of antibody therapy. This is obviously a thought that is on many minds so I guess I might as well chime in (again) with how we feel in a more public setting. Would we have done it again?

First off, before we get into the specifics of 3F8, ch14.18 or any of the other anti-GD2 antibodies, I think it is best to just address antibody therapy itself. Generally speaking, I have this to say:

I have seen kids with neuroblastoma. I have seen kids take antibodies. I have seen the disease in those same kiddos go away.

Antibodies kill neuroblastoma in kids.

Period.

I am often frustrated by the argument - "Well, there is no proof that antibodies increase survival." This bugs me for two reasons. First, it is wrong. There is some evidence. At the ANR in 2008 the Germans came out with a retrospective study on their use of the ch14.18 antibody and found that it appeared to show long term survival benefit. This is a study whose design was probably destined to fail. Yet, for some unknown reason, it is showing some long term success. So, in a nut shell, there is some evidence that antibody therapy improves survival. However, I would also gladly point out that it would appear unlikely that the ch14.18 study in the COG will show a survival benefit. I don't have any inside information here. It is simple math. If you look at the published survival curves for A3973 (the COG protocol Sydney was on) there was not a significant improvement in survival. With many of these patients undergoing antibody therapy you can begin to infer that antibodies must not have had a dramatic effect. That is purely speculation and given the small amount of patients on the antibody arm of this study I could be wrong.

Regardless, in my mind, this argument is relatively unimportant. We have to remember that we know that antibodies kill neuroblastoma in kids. Just like chemotherapy. Just like radiation. Just like just about any other therapy that has shown it could kill neuroblastoma. Do you think, individually, any of these single agents have shown an improvement in overall survival. Most, if not all, have not. Accutane is one of the lone exceptions. What most have shown, however, is that they have activity, that they have the ability to kill neuroblastoma cells. There is no measure of overall survival. We just know that the chemotherapy kills neuroblastoma and at what cost.

Just like antibodies.

So, in short, I don't like to get too hung up on the survival issue. Frankly, the answer isn't out there right now. We don't know its impact. Let's focus on what we do know - the facts.

We do know that antibodies kill neuroblastoma in kids. We can see that and measure it. It is not theoretical. It is a fact.

So, is all of the pain of antibody therapy worth it considering we know it kills neuroblastoma but that it may not impact survival? My thoughts?

You betcha.

We give mountains of toxic chemotherapy to our kids. Why? Because they kill neuroblastoma. We risk hearing loss, cardiotoxicity, neurologic problems and a litany of long term and short term very real side effects - just to kill neuroblastoma. So, in my mind, it makes sense to risk some short term pain, some hives, and some edema to kill some more neuroblastoma cells.

Another reason that we chose to do antibody therapy is because of how they work. Antibodies kill neuroblastoma differently than chemotherapy or radiation. They actually recruit the immune system to do the killing. Their is something romantic about training their bodies to kill neuroblastoma. Who knows whether their bodies remember it but the important thing to realize is that the immune system, the most powerful weapon we have, is killing neuroblastoma. It is icing on the cake if the immune system is acutally trained to continue this activity in the future. In some cases, it has also been shown that antibodies actually also do some of the killing for themselves. This is important.. By the end of therapy, our child's neuroblastoma has most likely developed some resistance to the chemotherapies that have been used to treat their disease. In other words, there are neuroblastoma cells that are resistant to chemotherapy. In order to kill these cells you need something that will overcome this resistance. Radiation can. Radiation is pretty good at killing neuroblastoma as well. However, radiation can only kill what is in the radiation field. So, even though it can be effective, it does absolutely no good for neuroblastoma cells that are hiding elsewhere in the body. The good news is that antibodies can kill chemoresistant cells that are out of theradiation field. Antibodies are systemic.

So, to make this long explanation really short. If one neuroblastoma cell was left in your child's body, if that cell was resistant to chemotherapy (likely) and if that cell was hiding somewhere outside of the radiation field then antibodies could kill that cell.

Antibodies are another opportunity to kill those hidden neuroblastoma cells that we can not see.

They aren't the silver bullet. They aren't the cure for neuroblastoma.

They are a tool and in one very unmedically trained father's mind a very worthwhile investment.

There are no guarantees and no promises, just another opportunity to try to defeat the monster.

It is for these reasons that, if we had to put Sydney through it all over again, we would do it in a heartbeat.

They are one tool in our super purpose toolbelt.