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Published on December 21, 2020
Multiple Myeloma Expert Discusses the Promising Future of Blenrep
Belantamab mafodotin (Blenrep) is an exciting new drug that has the potential to quickly change the treatment landscape of multiple myeloma. The recently approved therapy is currently being tested in combination with existing myeloma drugs, and clinical trials are seeing promising results. But how exactly does this new drug work, and what impact will it have on multiple myeloma treatment in the near future?
Leading multiple myeloma expert Dr. Paul Richardson, MD, Clinical Program Leader and Director of Clinical Research for the Jerome Lipper Multiple Myeloma Center at Dana Farber Cancer Institute joins us in this segment of our Answers Now series to share information on the groundbreaking new therapy, give insight into the clinical trials happening now and share his predictions on the emergence of Blenrep combination therapies in 2021. Patient Power co-founder Andrew Schorr guides the discussion on these new treatment advancements and other myeloma news from ASH 2020.
This program is sponsored by GlaxoSmithKline. This organization has no editorial control. It is produced by Patient Power, and Patient Power is solely responsible for program content.
Transcript | Will Blenrep Improve Myeloma Treatment Options in 2021?
Andrew Schorr: Hello and welcome to Patient Power. I'm Andrew Schorr in California. Joining us from the Dana Farber Cancer Institute is a frankly, world famous multiple myeloma expert joining us again on Patient Power and that is Dr. Paul Richardson. Dr. Richardson, welcome back to Patient Power. What's your title there?
Dr. Richardson: Well thank you very much, Andy. I serve as the Clinical Program Leader and as the Director of Clinical Research for the Jerome Lipper Multiple Myeloma Center and it's a privilege to be with you and it's a privilege to be here discussing some of the excitement around ASH. And again, thank you so much for having me.
Andrew Schorr: Sure. Well, thank you. I want to ask you about a specific drug, and it's been in a number of studies all called the DREAMM studies, trying to look at different combinations of where this drug fits in. First of all, what is this drug? How is it different in adding it to the multiple myeloma options? And then what are you trying to figure out with these studies to see how it works best?
What is Belantamab Mafodotin (Blenrep)? Will it Improve Treatment Options for Multiple Myeloma?
Dr. Richardson: Well, Andrew, as always, great question. It's belantamab mafodotin-blmf (Blenrep). Belantamab is the fun part of it, that's the antibody that targets BCMA and mafodotin is the warhead. That's a chemotherapeutic that's delivered to the tumor cell by the antibody.
Now DREAMM-1 provided us with a response rate just from the antibody alone of around 60% in that early phase study. And we also identified a dose and schedule. In DREAMM-2, led by my colleague, Dr. Sagar Lonial, actually from Emory. Sagar and us and others involved in that large study were able to demonstrate that there was a very solid response rate, but critically in a very sick population of patients. These were the so-called triple class resistant group of patients who have relapsed refractory myeloma and who have been typically what we call penta-exposed. What that means is they've had all the five major drugs that we have in myeloma and so therefore once these treatments have failed them, they're in a position of real need.
And what we showed was actually, whereas we showed 60% in DREAMM-1 as a response rate, a little bit lower, around 35% in DREAMM-2, but again, a much sicker, more vulnerable population. And what was really exciting was the duration of response in responding patients at a very well tolerated dose was around 11.3 months. So, to see a duration of response from off the shelf antibody that you just administer in the clinic of 11.3 months, in this particular cohort of patients, part of DREAMM-2, was really encouraging. DREAMM-2 was the sort of starting point of the approval and the accelerated approval then followed.
One of the challenges of belantamab mafodotin or Blenrep is keratopathy. It without a doubt causes challenging issues for the eye with blurry vision and this can occur in two thirds, up to 70% of patients in fact. The good news is the vast majority of it is mild to moderate and manageable. There is however, an important subset where it's more challenging and so we're working very hard to figure this out and minimize it, but it does appear to be dose and schedule dependent. And so in fact, if you can minimize the dose and adjust the schedule from every three weeks to perhaps longer, this side effect becomes much less of a challenge.
And the most important thing is that if you combine belantamab mafodotin with other drugs, things can really improve. And that's what's been so exciting. And we have the DREAMM-6 led by Dr. Ajay Nooka, from Emory where Ajay has shown really nice data with a higher response rate from that approach. And obviously, my colleague Dr. Suzanne Trudel from the Princess Margaret presented at ASH, really nice data on the combination of belantamab mafodotin with pomalidomide (Pomalyst). And so we're seeing the consistency of response from the belantamab plus standard drugs. And very importantly, we're working hard to figure out how to minimize the keratopathy. And in that spirit, we also presented some of our studies that are ongoing and one in particular that I'm very directly involved with is DREAMM-5.
In this particular study, we're trying to be even more ambitious. What we're doing is combining not only belantamab with actually an approved drug, isatuximab (Sarclisa), that's a CD38 targeted antibody. And that arm of the trial is in development right now. But we are already comparing belantamab mafodotin to belantamab combined with two antibodies and just a pill. And the pill is particularly interesting. I want to call it niro for short, N-I-R-O because nirogacestat is how you say it. I can never pronounce it. I apologize.
But anyway, niro is a pill that targets actually a thing called gamma secretase. And we know gamma secretase controls the expression of BCMA. And simply by combining belantamab mafodotin with a pill that's very well tolerated, it's actually a pill that was originally explored in of all things, Alzheimer's disease and was shown to be safe in Alzheimer's. Obviously, a safe drug because that's a vulnerable population, but unfortunately didn't work terribly well. Anyway, gamma secretase inhibition however, does matter to our patients because it up regulates BCMA expression and as a result of that can make belantamab work even better.
It's an ambitious study DREAMM-5. We're trying to do many things at once as it were, but frankly, I think it's the wave of the future because what we're trying to do is answer questions quickly because as all of our patients know with relapse refractory myeloma, time is of the essence. And so therefore these are very, I think, important platforms going forward.
Andrew Schorr: Wow. Thank you. Right. You're doing a lot of DREAMM studies sort of simultaneously adding to data and I appreciate that you're excited about this approach. And just so we're clear, BCMA is a target on the myeloma cells.
What is BCMA?
Dr. Richardson: Absolutely. Yes, great question, Andy. BCMA is what we call B-cell maturation antigen, and just as its name implies, it's a mature marker of a differentiated plasma cell. In the context of myeloma ontogeny, if you will, it's quite a long way down the maturation pathway, but it's definitively vitally important. It's clearly associated with resistance and survivorship of the tumor cell to establish therapy. Targeting BCMA is hugely important. As we know from not only the CAR T experience, which is looking so promising now, but also actually from the bispecific T-cell engagers, which really and again, the data at ASH were quite amazing in my opinion. Really exciting data from the BCMAs.
Andrew Schorr: Wow. You as a researcher, you're going after myeloma from a number of different directions. The DREAMM studies will give you information on new combinations and you have these other approaches you've alluded to. I think the news for myeloma patients, even people who've had many other treatments is more promising than ever.
Dr. Richardson: It is very promising. I think what we need to be very clear though, out of fairness to our patients with relapsed refractory myeloma and importantly their families, this is a very challenging area. Myeloma is extremely difficult to treat in the relapsed refractory setting and we deal with a patient population of exquisite unmet medical need, who are patients with highly resistant disease in whom this really matters. Really it's so good that we have so many options in development because we need every one of them.
Andrew Schorr: All right. Well, it certainly steps in the right direction and Dr. Paul Richardson, thank you to your peers who are involved in these studies and helping lead the way. Thank you so much for your dedication to patients, Dr. Paul Richardson from Dana Farber Cancer Institute.
Dr. Richardson: Thank you, Andy. My privilege. Thank you.
Andrew Schorr: I'm Andrew Schorr. Remember, knowledge can be the best medicine of all.
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