Tag Archive for: isatuximab

What Emerging Myeloma Treatments Are Showing Promise?

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What Emerging Myeloma Treatments Are Showing Promise?  from Patient Empowerment Network on Vimeo.

Myeloma specialist Dr. Mark Schroeder reviews the latest advances in myeloma treatment, including a discussion of CAR T-cell therapy and bispecific antibodies.

Dr. Mark Schroeder is a hematologist at Siteman Cancer Center of Washington University School of Medicine in St. Louis. Dr. Schroeder serves as Associate Professor in the Department of Medicine. Learn more about Dr. Schroeder.

See More from Engaging in Myeloma Treatment Decisions

Related Resources:

Multiple Myeloma Clinical Trials: Which Patients Should Participate

 Expert Perspective Advances in Treating Relapsed and Refractory Myeloma

 How Does Disease Staging Affect Myeloma Treatment Choices?

Transcript:

Katherine Banwell:

What about emerging therapies for myeloma? What approaches are showing promise? 

Dr. Mark Schroeder:

So, I think the biggest news in myeloma, and across a lot of cancers now, are immunotherapies. We know in myeloma – now we have two CAR T-cells –  

Now a CAR T-cell is engineering your own immune cell called a T cell to express a receptor on its surface that binds to the myeloma, and then those immune cells go and kill the myeloma. That’s a form of immunotherapy.  

There’s two CAR-T cells for treating myeloma after the myeloma has come back four times, has needed four treatments. Those are very active in that line of therapy, and we can see response rates over 80 percent in patients who otherwise weren’t responding to other approved therapies for myeloma.  

On the other hand, there are other immunotherapies that are used earlier in the treatment course of myeloma. One that is not incorporated more frequently for the initial treatment is a drug called daratumumab – it’s an antibody. It’s a protein that binds to the surface of myeloma and stimulates the immune system to react against the myeloma. And so, it’s not a traditional chemotherapy, but it’s using your own immune system to attack the cancer.  

And then a third one that’s probably just as – it looks just as potentially effective as CAR-T cells are called bispecific antibodies. And that would use a protein similar to daratumumab which is an antibody, but it uses parts of antibodies to bind to – it could be two different proteins – one expressed on a T cell, the other one expressed on the myeloma cells. And when it binds, it brings those two cells together and causes your own immune system to attack the myeloma. Those are also very effective, and within the next month or two, there will be a bispecific antibody approved for treating patients with myeloma. 

Katherine Banwell:

Oh, that’s great news. Any others? 

Dr. Mark Schroeder:

Yeah, well – I mean, the other potential – there are other immune cells called natural killer cells that are also in clinical trials for development to attack myeloma, and potentially even engineering those natural killer cells to attack myeloma.  

There are other antibodies; sometimes the antibodies of protein bind a specific target on the surface of the myeloma. I mentioned one – daratumumab – but there is a whole list of others that are in clinical development. The one other antibody – or two, couple of other antibodies that are approved for treating myeloma are isatuximab which also binds to CD38. And another one called elotuzumab which binds to a protein called CS1 or SLAMF7 on the surface of myeloma.  

That’s more information than you probably wanted or needed, but those antibody therapies can be very effective in treating myeloma. There is another antibody therapy that has a payload of a toxin on the antibody, and it binds to BCMA or B-cell maturation antigen.  

That’s the same antigen that the bispecific antibodies as well as the CAR-T cells are targeting on myeloma surface, and so that is potentially one that is approved by the FDA also to treat myeloma.   

Katherine Banwell:

As we close out our conversation, Dr. Schroeder, I wanted to get your take on the future of myeloma. What makes you hopeful? 

Dr. Mark Schroeder:

Well, I am hopeful – just within the last five years, there have been a number of new drugs approved for myeloma. They are approved for later lines of therapy, but they are being moved earlier in the treatment. And within the last 10-20 years, we’ve seen an improvement in the survival of patients with myeloma. As these new therapies are in development, as they’re being moved earlier in the treatment line, I’m very hopeful that survival and potentially cure for this cancer is possible. The only way that we’re going to get to that point is through clinical research and for patients to partner with their physicians and to consider clinical trials because that is the only way that new drugs get approved and are available to other patients with myeloma. So, I’m excited about what is approved; I’m excited about what’s coming through the pipeline to treat myeloma.  

Expert Perspective: Advances in Treating Relapsed and Refractory Myeloma

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Expert Perspective: Advances in Treating Relapsed and Refractory Myeloma from Patient Empowerment Network on Vimeo.

Dr. Abdullah Khan, of Ohio State University Comprehensive Cancer Center – The James, reviews currently available treatments as well as those in development for patients with relapsed or refractory myeloma. 

Dr. Abdullah Khan is a hematologist specializing in multiple myeloma and plasma cell disorders at the Ohio State University Comprehensive Cancer Center – The James. Dr. Khan is also an assistant professor in the Division of Hematology at The Ohio State University. Learn more about Dr. Khan.

See More from Engaging in Myeloma Treatment Decisions

 

Related Resources:

How Does Disease Staging Affect Myeloma Treatment Choices?

 Expert Perspective Why Myeloma Patients Should Weigh in on Their Care Decisions

 Relapsed and Refractory Myeloma Defined

Transcript:

Katherine:

Are there any recent advances in treatment for patients with relapsed or refractory disease?  

Dr. Khan:

Currently and in the past 20 years or so, we’ve seen about 20 approvals for new drugs for patients with multiple myeloma. The way the approval process works it typically looks at the effectiveness of a drug in the relapsed refractory setting first. And after establishing the safety and efficacy, the therapies are moved earlier in the disease course.   

The great example of this are the anti-CD38 monoclonal antibodies daratumumab and isatuximab. They were first approved in the relapsed refractory setting in combination with other antimyeloma treatments. And due to their impressive effectiveness and relative safety, they’re already being used in the frontline setting for patients with newly diagnosed multiple myeloma.   

In the newly diagnosed setting, a commonly cited study is the phase two GRIFFIN trial. And that added daratumumab to the BRd, or bendamustine (Bendeka, Treanda), lenalidomide (Revlimid), dexamethasone backbone.  

And Europe, they completed the phase three study of adding isatuximab, the other anti-CD38 monoclonal antibody to the BRd backbone. And what we’re finding what was very effective in the relapsed refractory setting was actually adding to the efficacy of newly diagnosed treatment regiments. As a side note, these trials – there are also trials looking at daratumumab and isatuximab in the smoldering myeloma phase, so moving it even earlier.  

I think one of the most attractive new targets in myeloma is targeting this antigen called B-cell maturing antigen, and a number of therapies are being developed or are already developed for it. The first approved was belantamab mafodotin, and this is an antibody drug conjugate. 

So, when the antibody binds to BCMA on the multiple myeloma cells, it releases its toxic payload into the myeloma cell. And so, it’s very effective towards myeloma, and no other good cells or fewer other good cells are affected by it. To provide some numbers, in patients with a median of seven prior lines of treatments, meaning their myeloma had relapsed that many times, the response rate was about 30 percent. And a fifth of those patients had VGPR, very good partial response, or better response.  

There are also bispecific antibodies that target this myeloma marker, and we anticipate getting one approved soon in the U.S. called teclistamab. Teclistamab is an antibody that binds both CD3 on T cells of the immune system and B-cell maturating BCMA on the myeloma cells. 

So, the way this antibody kills myeloma is by activating the T cells, the immune system, and directly killing the tumor. So, this was recently published in the New England Journal of Medicine. And in people who were treated with at least five prior lines of therapy, the response rate was about 63 percent, and the median progression-free survival, or the time until the myeloma progressed, was about 11 months.  

We were very active in a clinical trial looking at the effectiveness of another antibody, a bispecific antibody, called Regeneron 5458. In a similar patient population, the response rates were 75 percent in the higher-dose level group, and right now it’s actually a bit too early to tell how long the progression free survival is or the duration of response. 

There are also other bispecifics in development targeting other myeloma markers ssuch as talquetamab, that binds to a marker called GPRC5D, and cevostamab, which binds to a marker called FcRH5. The response rates as single agents in patients with relapsed refractory multiple myeloma are 66 percent and 45 percent respectively. These are all incredible numbers for a single drug in the relapsed refractory setting.