Advances in Multiple Myeloma from EHA 2013

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Published: 2 Jul 2013
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Prof Gareth Morgan - The Royal Marsden Hospital, London

There are several new treatments available for the treatment of multiple myeloma (MM), including the new proteasome inhibitors. Other new treatments include ARRY-520, which is a potent, selective kinesin spindle protein (KSP) inhibitor; its mechanism of action is distinct from other drugs used to treat MM, and it has shown activity as a single agent. Daratumumab (anti-CD38 antibody) has also shown promise as a single agent and in combination therapy regimens. The antibody therapies are generally well tolerated. There is a pipeline of new therapies that will be expected to become available in the next few years, including pomalidomide, antibody treatments and small molecule treatments. In the UK, Myeloma UK plays a very important role in aligning patients to appropriate clinical trials. Myeloma UK is currently funding a programme to look at the genetics of MM in order to target treatments appropriately.

18th Congress of EHA

Advances in Multiple Myeloma from EHA 2013

Prof Gareth Morgan - The Royal Marsden Hospital, London

What new drugs are available for the treatment of multiple myeloma?

There are loads of small molecules out there these days and part of their role that someone like me wants to pursue is to lever new drugs into the area of myeloma. So it’s important to review the early preliminary data. It seems to me that now there are three good sets of data supporting developing these three different agents in the area of myeloma because as single agents they show significant activity. So, pretty much, if you take those three agents forward and try and target them at specific groups, develop rational combinations based on their mode of action we should be able to actually get them into the area of myeloma without too much difficulty. So for patients they look like a significant step forward to me. We’ve had the new generation of proteasome inhibitors, the new generation of IMiD drugs and these three agents look as if they will be good.

So we should talk about what the agents are, of course, and there’s one called ARRY-520 which is a kinesin spindle protein inhibitor which is a totally new mode of action that inhibits the cell when it divides. As a single agent they seem to be active in a significant proportion of relapsed refractory myelomas which is very exciting. We’ve always wanted to build a combination with an antibody as well and there was an antibody HM 1.24 that we were excited about years ago and it didn’t pass the hurdle to be moved into the clinic. But daratumumab, an anti-CD38 antibody, seems to be an agent where we can really expect to see activity both as a single agent and in combination. So the idea will be we’ll build a myeloma CHOP-rituximab and daratumumab has all of the characteristics that would allow us to do that, I think.

How well are the new investigative therapies tolerated?

The interesting thing about them is that the antibodies are really well tolerated, the infusion schedules are not too intensive and people could stay on them a long time. Because that’s one of the other important messages coming out is it’s not high dose for a short period of time, it’s duration of time on treatment also seems to be very important in myeloma.

For elderly patients we’re all waiting for the results of the RD versus MPT study and hopefully if we see activity with RD, which is well tolerated, you could start to add antibodies in to a backbone of an IMiD drug that’s really well tolerated. Because it’s not so much for the elderly because a lot of elderly patients are fit and well, it’s for the frail elderly where we’ve struggled to get new treatments into them. Maybe these kinds of IMiD and even proteasome antibody combinations are going to be highly effective in that group of patients.

What drugs do you expect to become available in the next few years?

We do have a pipeline that will become available in the next 4-5 years; it’s not something that’s drying up. The oral proteasome inhibitors with different modes of action are going to be there, the new IMiD drugs – pomalidomide is going to be there, they’re both about to be approved. Those will be followed on by antibody treatments and then subsequently these small molecule inhibitors. So I think there is a lot of excitement that we will get these drugs into the clinic for patient use in a timely fashion.

How are organisations such as Myeloma UK helping to bridge the gap between patients and the clinical community?

Myeloma UK is doing a terrific job in bringing patients and patient priorities together with physicians and physician priorities so it’s all aligned seamlessly. Part of their plan is to have a preclinical drug evaluation science translation and science set-up, a clinical trial group that’s able to move drugs rapidly from the preclinical to the clinical. But the groovy part about their plan is to build a translational programme that takes you from the phase II to the phase III and then registered drugs. So by working with NICE during the early phase of drug development you should be able to get the drugs from study, so it’s great knowing that a drug is useful in a phase III study but then there’s this big hole where the patients don’t get it for maybe three years. So by bringing NICE in early into the process it should be that we will seamless get drugs from the laboratory to the patient in a very rapid time. I think this is a very innovative model; I think there are lessons for the rest of Europe involved in it and for the US. It’s very important as this economic crisis, the amount of money available is less, but if you build a plan I think we can carry on as if there was no economic crisis by being organised.

Myeloma UK is sponsoring funding a programme in looking at the genetics of myeloma and how you can use those to target treatment appropriately. Because that’s the other big area – bringing additional value to drugs by only using them in the patients who are going to respond. The paradigm there is if you have a 20% response rate that’s not a very valuable drug at one level. If you can identify a group of patients where 80% of people will respond, say, that suddenly becomes a very valuable drug because the patients are responding, you’re not exposing patients who may get side effects who aren’t going to respond and the pharmaco-economic considerations mean that it’s actually more affordable as well.