Examining strategies to tailor multiple myeloma immunotherapy

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Published: 2 Mar 2017
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Dr Jeffrey Zonder - Karmanos Cancer Institute, Detroit, USA

Dr Zonder talks to ecancer at the 16th International Myeloma Workshop about emerging strategies tailoring immunotherapy to individual patients with multiple myeloma.

Immunotherapy for myeloma is also discussed by Dr Lesokhin here.

ecancer's filming has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

We’re talking about ways of tailoring antibody therapy using recently approved antibodies in multiple myeloma. We talked mostly about daratumumab and elotuzumab; I’m also going to talk a little bit about emerging antibodies with the same targets so isatuximab and MOR202 as well as the conjugated antibody that targets SLAMF7.

Are your findings promising?

What we’re seeing already, we’re seeing a lot of data at this meeting. I entered ASH last year and published recently about combining these antibodies with standard therapies. The data that’s out there now is in the relapsed setting and we’re starting to see these move forward quickly. We’re beginning to see some preliminary results from upfront studies so we’re combining drugs like elotuzumab and daratumumab with standard frontline regimens like RVD. There’s an expectation that those are going to have a really big impact on the efficacy of those regimens.

In my talk I mentioned the fact that there are numerous ongoing trials utilising each of these antibodies together with regimens like RVD, with CyBorD, with Rev-dex and we’re going to be getting readout on those studies in the next one or two years.

What impact will immunotherapy have in treating myeloma?

It’s going to have a really big impact. We’re seeing both daratumumab and elotuzumab have a major impact on duration of response. Both of them seem to have that activity in higher risk patients, patients that traditionally don’t have the durable responses from chemotherapy. And we’re seeing, particularly in the case of the anti-CD38 antibodies, we’re seeing a deepening of response so they’re not just longer responses but there are more patients who actually reach an undetectable disease state, minimal residual disease negativity, which is, right now, really a holy grail in multiple myeloma. To cure patients you have to render their disease undetectable so getting a sizable number of patients to that state now is a major leap forward.

Have you seen any complications in combining immunotherapy?

So far the toxicity profile is really remarkably benign. Both the approved antibodies have infusion reactions associated with them but, to be honest, a lot of the toxicity we’re seeing is the result of being able to be on therapy for longer, so just longer exposure to therapy but it doesn’t make the regimens dramatically more toxic. So it’s almost all upside.

What are the conclusions of your talk?

The conclusion of my talk is that we’re entering an era where antibody therapy is going to be utilised in first or second line therapy for almost all patients. By incorporating them into those regimens we’re expecting longer and deeper responses, including patients who traditionally didn’t benefit as much from chemotherapy. We’re going to see more non-transplantable patients get to those deeper responses than we’ve ever seen before. The other thing we’re going to see, which I touch on in the talk, is we’re going to start seeing these antibodies used in multiple lines of therapy most likely with different partners than the ones that we’ve already studied in randomised studies. We’re going to start utilising these antibodies with pomalidomide and carfilzomib and other drugs as part of later line therapy as well.

Is there potential for more trials in future?

Right now there are several dozen trials with each antibody ongoing and, like I said, we’re going to be starting to see readout from some of these studies in the next year, year and a half.