[Greg H]

Hi Nadia & Hopeful!

Hopeful makes a passionate defense of ATG/CsA vs. Campath based on her own success with the former. Given that Campath failed to fix my own problem, I'm not sure I can be quite as passionate.

I can, however, offer some data. Dr. Elaine Sloand's team at NIH published a study of IST in MDS in the Journal of Clinical Oncology in 2008 that, among other things, established the superiority of the ATG/CsA combo over either drug used alone. Of the 129 patients treated, 30% responded. Among those who got both ATG & Cyclosporine, the response rate was 45%.

Among INT-1 patients who got both drugs, response rate was 54%.

The same team mounted a trial of Campath in MDS patients and reported in JCO last November a response rate of 77% among INT-1 patients.

So, let's look at the scoreboard for the best responders, the INT-1 patients:

ATG+CSA - 54%
Campath - 77%

Looks like a clear win for Campath, no?

Well, not really. You see, the response rate you get depends on the patients you start out with. If you can narrow down the folks who are most likely to respond, and only let them in the trial, you are going to get better numbers than if you take a broader range of patients.

The 2008 paper on ATG+CSA is based on a much wider set of patients. Sloand and her team used what they learned in that study to create a filter for the Campath study, accepting only patients who had a strong probability of response. So, the Campath response rate would have been higher, even if it only worked as well at ATG+CSA. Using data from the earlier study, their regression model predicted that INT-1 patients under 60 with HLA-DR15+ had a 67% probability of response to ATG/CSA -- not far off from what they got with Campath.

Hopeful's impression that Campath for MDS has an inferior response rate is not supported by the data. The data suggest, instead, that Campath is equal to ATG/CSA. As far as I know, the November 2010 JCO paper by Sloand's group at NIH is the only paper out there on Campath for MDS, but it could be that Hopeful has data from another one that we need to include in our deliberations.

There was another NIH trial of Campath for relapsed Severe Aplastic Anemia that got poor results (although not for one marrowforums member), but that's a different disease and a very, very different set of patients -- who had already relapsed once.

There can be some degree of overlap between MDS and AA -- or, maybe, some uncertainty about which diagnosis applies in a particular individual. Hopeful's signature suggests just such a case, and my newly-discovered TERT mutation may be another. But I think it would be a mistake to assume that all hypo-MDS is the same as AA.

Both of Sloand's studies on IST specifically excluded folks who had a prior diagnosis of AA -- and that means the results might not apply to folks sitting firmly on the AA-MDS fence.

I don't really think, at this point, we know whether ATG/CSA or Campath is better; they seem pretty comparable. Sloand's paper says she decided to give Campath a go because of the nephrotoxicity of cyclosporine -- that is, it's hard on the kidneys. And there's the whole issue of how you taper it correctly, which seems to get talked about a good bit here on marrowforums.

So, what's a patient to do?

Try to learn as much as you can about the options, understand the response rates and how well those correspond to your individual disease profile, take a look at the side effects and other potential downsides, pay your money, and take your choice.

I have copies of both the JCO studies I referenced here (as well as the summary of the poster presentation on the SAA Campath study from ASH last year) and would be happy to send them via email.

Take care!

Greg