ASH 2014

Anti-CD38 antibody SAR may be new "blockbuster" treatment for aggressive multiple myeloma

Dr Thomas Martin, MD, University of California, San Francisco, USA

There are a lot of targets or antigens on the surface of the plasma cells, one of them that is highly expressed is this receptor CD38. So this antibody binds to the plasma cell and many antibodies bind and that may provide a more robust immune response, what we really want. The antibody just holds a flag up to the immune system, it says, “Come get me.” So there are a lot of receptors on the cell surface in myeloma which is a good thing.

What sort of patients were you trying to treat here?

In this study we had relapsed and refractory patients and in fact we did not have any limitations on the number of prior therapies. Many patients with myeloma go through quite a few numbers of therapies through their myeloma lifespan and so the average number in this group was four. This was a really heavily pre-treated patient population.

So if they didn’t have this treatment, what was their outlook?

If they didn’t have this treatment their outlook honestly is an overall survival of about 9 months.

What did you do in the study?

In this study we combined the anti-CD38 antibody with one of the other novel drugs in myeloma, lenalidomide or Revlimid. Now Revlimid is a typical anti-myeloma drug, however in this study 84% of the patients were refractory to Revlimid. But the other thing Revlimid does, it stimulates the immune system. So it tells the immune system, the macrophages and the NK cells, “Go find these antibodies, bind to whatever is bad and let’s kill it.” So it was a nice combination, we’re looking for synergy.

So what happened? You had 31 patients, what happened and how did the study proceed?

We treated 31 patients with this combination. They tolerated the combination quite well; there were no untoward side effects that we saw. In terms of response rates, in the whole population 58% of the patients had a response, that’s a partial remission or better. If we include some of the minor responses it actually goes up to 62% and if we take the highest dose of antibody, because in a phase I study you start at a lower dose and you go up to medium dose and then a high dose, if we just look at the high dose basically 63% of the patients responded.

Now, a relatively small number of patients so we can’t read too much into it but if your hopes are fulfilled what do you think this could imply clinically?

It’s a really good question. This is preliminary data for sure because it’s a small number of patients but it certainly is a signal or a sign that this antibody is active and it’s especially active when it’s combined with one of these immunomodulatory drugs. The hope is that this study can be done in a larger patient population, even in a randomised fashion where half get just the Revlimid and dexamethasone and half get the antibody, Revlimid and dexamethasone, so we can prove the three drug combination is better than a two drug combination.

There have been big improvements in multiple myeloma over the last decade or more, could this one make a difference do you think?

Yes, in myeloma today we have two drugs which I consider are blockbuster drugs, drugs that really have good activity. Those are the IMiDs, like Revlimid or pomalidomide or Pomalyst, or the proteasome inhibitors like Velcade, which is bortezomib, or carfilzomib, Kyprolis. This would be a new and a novel blockbuster class of medicine so this would add a dramatic improvement to our armamentarium for myeloma.

What should doctors be making of your preliminary findings now?

I think a lot of doctors should be encouraged by this result and by the results of the antibodies as single agents. Doctors and patients alike should be referring patients for clinical trials, investigating further these anti-CD38 antibodies, more phase II trials, phase III trials so we can get this antibodies to FDA approval.

So CD-38, an important part of the multiple myeloma molecule. What should people take home from this right now?

The take home is this is preliminary evidence that these drugs are active, they’re well tolerated, there’s no neuropathy and that in the future it’s going to be one of those drugs that’s going to be used widely throughout patients getting front line therapy for myeloma, transplant for myeloma and relapse therapy for myeloma.