Wednesday, January 20, 2010

In relapse, there really is only one antibody option

Every once in a while I have to come out with a controversial post that I am quite sure is going to make people downright mad. This is one of those posts. Now remember, I have absolutely no medical training. I am just a dad. I have no right to dispense medical advice or give anyone any direction what-so-ever as it relates to neuroblastoma or its treatment.

Still, I am right.

Today's rant has primarily to do with the use of antibodies in the relapse setting. Now, with any story there are caveats. However, I am dealing with a specific scenario and I think it requires some deep thought. I am not talking about the hundreds of possibilities that exist outside of this scenario. I am also not talking about children that have not relapsed. My thoughts on that topic would be different.

Enough said. Now, onto the story.

There have been many oncologists, some of whom I respect deeply, that have been advising patients to participate in the phase 1 hu14.18 antibody study offered at St. Jude's over going to Sloan for 3F8. While I do wish there were other and/or better antibody options for children with relapsed neuroblastoma (and I can think of many), as of this writing, these are the only 2 options we have. Even with this, I don't really believe that it is really an option.

I will tell you why.

The version of hu14.18 that is being offered at St. Jude's comes along with some trial design issues that make it almost entirely worthless. I am not saying that the antibody itself is worthless. In fact, I can make some pretty good arguments that it could, in fact, be one of the best. Unfortunately, in the way that it is being delivered in this trial I don't think it is in most relapsed kiddos best interest.

First,the trial is only being offered to children with measurable disease. The problem that we run into here is that measurable disease is often too much disease for an antibody to handle on its own without something else along with it (like radiation, NK cells, or chemo), in high doses, or for long periods of time; none of which does the hu14.18 trial at St. Jude's offer. In effect, the trial design is preventing the kids that would benefit the most from participating at all and favoring the ones it is probably least likely to help.

Second, as I understand it, they are only offering 4 rounds of the stuff. While I can't point my finger to published data, I think everyone feels pretty solidly that 4 rounds is probably too little antibody to do the job - especially for people with measurable disease. It is this problem that is one of the reasons that the COG modified their hu14.18/IL-2 antibody trial to allow patients to receive up to 10 rounds when they showed some response. I don't know if this is something that has changed with the St. Jude trial but it is a big fallacy when trying to win the battle with the disease. Finally, there is a lot of evidence by MSK which shows that patients tend to do better when they receive more than 4 rounds of antibody. It isn't enough drug. Period.

Third, it is a phase 1 trial. Trust me, I am a huge advocate of phase 1 trials. However, when you have a phase 2 option that is relatively proven, I can't understand why you would submit yourself to a phase 1 dosing trial unless you had no option. If we are truly trying to save kid's lives who have relapsed and have a real shot at a potential cure then the hu14.18 trial simply is not the right weapon to try to consolidate the remission. Look, I am not going to argue whether or not antibodies can replace a transplant. However, they have had some success and in a population that is probably not going to (and probably shouldn't) transplant a second time antibodies remain one of the only options with a proven track record of keeping kids in long term (maybe permanent) remissions.

Look, I like St. Jude's. I like the researchers. I just don't think this trial is in the best interest of most kids who are searching for their second "cure." If you have relapsed and if you have had chemo and/or MIBG and/or a slew of other treatments and you are in or nearing your second remission, antibodies should be on your radar. I just don't think there is any option of where to go in this case.

In this case, 3F8 is the clear winner because of the way that it is delivered, its track record, and its variety of options.

Sometimes you just have to be honest about purpose.

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