Dr. Don Benson, MD, PhD
Ohio State University
Interview Date: September 18, 2015
The world of potential multiple myeloma immunotherapies is growing. Dr. Don Benson of Ohio State University shares his deep knowledge of the field. He reviews the four classes of immune therapies – 1) cellular therapy like transplant and CAR T cells 2) monoclonal antibodies 3) cytokine treatments and 4) vaccines. He first reviews the upcoming monoclonal antibodies, which are expected to be FDA approved soon. Elotuzumab will likely be the first approved before year-end and targets the CS1 protein. On its heels is daratumumab, which targets the CD38 protein. In the field of monoclonal antibodies, he describes two classes – the first stick to the myeloma cells themselves and either kill myeloma directly or flag the immune system to kill them. The second stick to immune cells in the body and can change their function. Can these be used together? Yes! He shares a study to use both kinds of monoclonal antibodies. He also notes that the personalized nature of their use may be critical. As an example as part of a isatuximab trial, he found that for certain patients that showed a certain inhibatory receptor on their cells, 90% of them responded to this immunotherapy while 50-60% of the others in the study responded. He shares that knowing BOTH your genetics and your immune system features will be critical to getting truly personalized care. With these upcoming drugs, he discusses how expanded use and compassionate use programs work and how patients can find more information. He discusses the excitement around CAR T cell therapy, with recently published results in the New England Journal of Medicine showing that this type of treatment may have killed the myeloma stem cell clone – the source of relapse. There is much to learn and be excited about in this important show.
Clinical Trials Discussed in This Show
The Myeloma Crowd Radio Show with Dr. Don Benson
Jenny: Welcome to today’s episode of Myeloma Crowd Radio, a show that connects patients with myeloma researchers. I’m your host, Jenny Ahlstrom.
Now, before we get started with today’s show, I want to let you know that we are now in full swing for our Myeloma Crowd Research Initiative, which is a patient-driven crowdfunding initiative. As patients, we can’t wait for a cure. This is the first time that a united group of patients have teamed up with an expert group of myeloma doctors to select two specific projects to fund for high-risk multiple myeloma. High-risk patients do not respond in the same way to today’s treatments as standard or low-risk patients. We need to find new and potentially curative treatments.
We used an eight-month process to find the best projects and have now selected two to fund. We are raising $250,000 for each project and we need your help. Today, you can go to give.crowdcare.org/mcri and donate or create your own personal fundraising page to share with your family and friends.
What’s very exciting about these two projects is that they are immunotherapies. Today’s show is dedicated to this topic and Dr. Don Benson will give us a very excellent overview of everything that’s happening in this field. It’s very exciting.
It’s also completely fascinating that although these two projects we selected are specifically for high-risk patients, they will be equally effective for low or standard risk patients.
Now, all of the funds raised will go directly to these two projects, so donors will know exactly where their donation is going. And as Gary Petersen, a myeloma patient says, “This is a way we as patients can help save ourselves because we can’t afford to sit back and wait for cure.
We would also like to thank Takeda Oncology as our episode sponsor.
Now, on to today’s show, we are delighted to have Dr. Don Benson with us today to discuss this brave new world of immunotherapies for multiple myeloma. Options are expanding and he will give us important overview and also kind of a deep dive into some other topics that relate.
So, Dr. Benson, welcome.
Dr. Don Benson: Hi, Jenny. Thanks for having me.
Jenny: Well, thank you for joining us on the show. Let me give you a little introduction before we get started. Dr. Benson joined us two years ago, so we have a lot to catch up on in the last couple of years.
Dr. Benson is Associate Professor of Medicine and Coordinator of Education in the Division of Hematology at Ohio State University. He’s a member of the ASCO Committee for the Oncology Training Programs, a member of the Ohio State Residency Training Program, Core Competency Review Committee member and Fellowship Candidate Selection Committee member.
His recent awards include the Henry Kunkel Society for Immunology in 2015, Champion of Family Medicine Award, Gold Humanism Honor Society, Excellence in Teaching Award, Courage to Teach Award, Professor of the Year and ASCO Merit Award to just name a few.
His research emphasis is specifically in immunotherapy for cancer, in particular, multiple myeloma and other blood cancers. His research laboratory performs research seeking to recover or augment normal immune system functions as a means to eliminate cancer cells using a variety of methods like cytokines, antibodies, immnunomodulatory agents and new small molecule targeted therapies.
These studies complement therapeutic clinical trials in the conventional setting and around stem cell transplants. His studies includes early phase I and beyond.
So, Dr. Benson, welcome again.
Dr. Don Benson: Thanks, Jenny. I appreciate it.
Jenny: Maybe you want to begin by just giving us categories of immunotherapies because the list is ever expanding, it seems.
Dr. Don Benson: Sure. It can get very complicated very quickly, and I think there are different ways that we can approach the topic of immune therapy for cancer. I think one way that might make the most sense is by modality or the differences in terms of how these are conceived and created. There’s one general category of immune therapy called cellular therapy and this is a category where stem cell transplant would fall.
Autologous stem cell transplant is a form of cellular therapy when we use a patient’s own stem cells. Donor transplant is a form of cellular therapy. You can maybe think of donor transplant as the ultimate immune therapy in essence because you’re literally taking the immune system from one person and giving it to another.
The other major category of cellular therapies that’s emerged just since we spoke last I think has been the area of CAR T-cells and CAR NK cells or chimeric antigen receptor cells.
There’s a big class of immunotherapy that utilizes monoclonal antibodies, and these are small proteins that are manufactured to do a specific purpose or serve a specific function. So these are proteins that are aimed at antigens that are expressed either on the myeloma cells or immune cells or other targets in the environment, in the cancer environment, each with the different purpose. So there are literally dozens of targets that have been identified in myeloma alone that you could attack with the monoclonal antibody.
They work different ways. Some antibodies are designed intentionally to stick to the myeloma cells themselves and they can cause the myeloma cells to die either directly by sticking to them or by serving as a flag to recruit other immune cells to come and eradicate the myeloma cells. And then there’s a whole second class of antibodies that don’t attack the myeloma cells directly but rather stick to specific immune cells in the body, and in doing so can modulate their function.
So the first wave of these antibodies, and really the first wave of immune therapy in general, have all been attempts to stimulate the immune system or to step on the gas, and so there’s a whole class of those. And then one of the really exciting fields in immunotherapy in general, not only in myeloma but in all cancers, has been the development of antibodies that disinhibit the immune system. So it is kind of a complement of what we just mentioned that these are antibodies that are meant to take the brakes off, to release the immune cells from inhibiting signals. So it’s kind of like taking the safety off of a gun, if you will.
And then there’s the third class of antibodies that target other factors in the micro environment. I just counted this morning there are at least 17 different antibodies in clinical trials right now for myeloma alone with more to come. There’s a whole separate category of immune therapy that’s all vaccine based, and so you can think of these just like vaccines for infectious diseases, for measles or mumps or the flu or whatever. Vaccines are a way to try to teach the immune system what a myeloma cell looks like, so they can kill these cells more effectively, and not only that but keep it from ever coming back again. So there’s a variety of different vaccine strategies that are out there being developed. Some of them are cellular, some of them are protein based. But they all have that same somatic similarity of teaching the immune system how to function better on its own.
And then a fourth big class are cytokine-based therapies. These are drugs that are given therapeutically either to mimic in effect of a signal in our own immune system, or I think the most exciting one right now is an engineered cytokine that’s been designed to have a greater effect or an augmented effect when it’s used to treat cancer. The four big classes are cellular therapies, antibodies, cytokine and vaccines.
And then just to complete the list, some of the drugs that we already have approved, can have immunomodulatory strategies, so thalidomide and lenalidomide or Revlimid, pomalidomide or Pomalyst. And even drugs like Velcade, for example, have all been shown to be able to influence the immune response in addition to their direct anti-myeloma effects. So it’s a very complicated field, it’s a very crowded field, but I think those are good issues actually. There’s an awful lot going on in immune therapy for myeloma right now.
Jenny: Well, it’s exciting to see that there are other options that are being pursued, that are focusing on less chemo and more enhancing your immune system to do its job, as a patient anyway. That’s my opinion.
Dr. Don Benson: I agree with you. I think that it might be helpful to characterize immune therapy in the context of other treatments that we have at our disposal. We have chemotherapy. We have what you could call good old-fashioned chemotherapy and those are drugs like melphalan for example that kills cells that are dividing. We know that in general cancer cells divide faster more readily than normal cells and they provide a target for drugs like melphalan or doxorubicin to kill them because they’re dividing quickly.
The problem with is that is it’s really a nonselective approach. It kills all dividing cells. That’s why people lose their hair. That’s why people get diarrhea. You could actually say close to the same thing about radiation treatment too. It’s a great treatment for myeloma, but it kills a lot of other healthy cells too. There’s a lot of collateral damage with those treatments.
One of the attractive things about immune therapy is that if we can get it right, you can explicitly target the tumor cells using the healthy cells against them.
Jenny: Right, that’s fabulous. Well, in terms of these different categories, the cellular therapy, monoclonal antibodies, vaccines, cytokines and then these existing drugs that we have, is there one you want to start with and we can dive into a little bit more detail?
Dr. Don Benson: Oh boy! How much time do we have? Why don’t we talk about the antibodies first since I suspect the next wave of approvals and availability of these will be the antibodies? And then we should try to save some time to talk about the CAR cell stuff too. There was a great paper in the New England Journal last week for CAR cell therapy for myeloma. I don’t want to limit our conversation on these other topics. They’re just as exiting. But I think we should maybe focus on the antibodies first since there’s a couple that will hopefully be approved soon.
Jenny: Yes, I think so. So maybe you want to talk about those specifically and then when they’re anticipated, how they work and how you would be using them in the clinic.
Dr. Don Benson: Okay, great. So the first one is a drug called elotuzumab, and this is a monoclonal antibody. It’s a small protein that sticks to the surface of myeloma cells. It sticks to a protein that’s had different names over the years. The first name of it was CRACC. It was called CS1 for a while. It’s also called CD319. And most recently it’s been named SLAMF7. But anyways, if someone was to go on the internet they might see any of those associated with elotuzumab. They all reference to the same protein.
Elotuzumab binds to SLAMF7, and in doing so, it serves as a flag for the immune system. It flags these cells that it’s being abnormal and candidates for immune-based removal from the system. Almost all myeloma cells have SLAMF7 on their surface, and so it presents a very ubiquitous target for the immune system to recognize and attract these immune cells to the myeloma cells.
The immune cells have a receptor for elotuzumab so they can recognize when elotuzumab is bound to a target, and that facilitates the immune cell’s ability to kill that cell. The immune cell that does the business end of this arrangement is a class of cells called natural killer cells or NK cells, and they actually were named in the early ’70s specifically as natural killers because of this phenomenon that was observed in the laboratory that these cells could kill tumor cells spontaneously. So unlike other immune cells that need a co-stimulatory signal or need to undergo gene rearrangement or need to be primed in some way, natural killer cells could kill cancer cells very efficiently and very quickly and repeatedly as soon as they recognize the cancer cell as being abnormal. And so elotuzumab works by facilitating that action, that activity.
We have been involved with elo’s development here at Ohio State for a number of years. We’ve worked with it in the laboratory and have also found new ways elo works. Elo actually works to stimulate NK cells as well as identify targets and maybe has a third mechanism too in optimizing the spatial relationships or the interface between NK cells and myeloma cells.
The phase III trial of elotuzumab was published back in June in the New England Journal, and it was a randomized study where half of the patients got Revlimid and dexamethasone and the other half got Revlimid, dexamethasone and elotuzumab and showed that not only was the response rate higher but the remission length was higher and the survival endpoints were improved with the addition of elo.
It’s a very interesting study. We hope that that study would justify its approval in the United States and in Europe. I think even though there’s been almost a decade of research put into elo, we’re still not maybe at a point to say where it would be most effectively used. In fact, we still have an open elotuzumab trial at our institution right now. When it was given by itself without any combination, it had very modest activity, if any. But when given in different combinations, so for example with Revlimid or we published another trial where we gave it with Velcade, we saw additive or even potentially synergistic benefit with these combinations.
So we still have a lot to learn, but elotuzumab, I think, will become the first FDA approved antibody therapy for myeloma and in fact would join probably close to three dozen FDA-approved antibodies for other types of cancers and conditions. So we’re really excited about that one.
Jenny: And when do you expect that?
Dr. Don Benson: Yesterday? It can’t get here soon enough and for a variety of reasons. I think that I would like to see that it would be approved by the end of the year, by the end of 2015. I haven’t heard rumors of an official date yet, but it was granted accelerated approval at the FDA. And like I said, the research showing its benefit is finished and published and is out there. Hopefully it will be not long. Hopefully it will be in the next couple months that elotuzumab will be out and available.
Jenny: That’s great. I have a question – you said that it has been tested with Revlimid and with Velcade. Has anyone tested it with both Revlimid and Velcade?
Dr. Don Benson: Yes, in fact, there is a trial using DRd and elotuzumab and the phase I portion of that was published online anyway. It’s not in print yet. But that four-drug combination is even being studied in newly diagnosed patients now, so there’s limited data that’s been presented in meetings and published so far. But that’s certainly I think where people want to see this drug go is into these multidrug, very effective combinatorial therapies.
Jenny: Yes, it seems to be quite common just to use all these drugs together, and I just was curious about that.
Dr. Don Benson: Yes, there’s a practical advantage with the antibodies because they don’t have the same off-target effects. So they may not be as myelosuppressive, for example, as a traditional chemotherapy drug or even in an immunomodulatory drug or proteasome inhibitors. So adding these on to established backbones could bring added benefit without added risk, if that makes sense, or added side effects.
Jenny: No, it does. The fewer side effects, the better. So that’s the elotuzumab. So elotuzumab targets the CS1 protein, right? Is that correct?
Dr. Don Benson: Correct.
Jenny: And that target was selected because ?
Dr. Don Benson: CS1 was selected because it’s so frequently and so highly expressed. It’s virtually on over 99% of myeloma cells, so it’s a very commonly and richly expressed target on the tumor cells themselves.
And the same could be said about daratumumab too, actually. So you mentioned daratumumab. This is also a monoclonal antibody.
So just for the listeners, any drug that ends in MAB, the letters M-A-B, is probably a monoclonal antibody. And then there’s a really interesting nomenclature as to how they come up with the name of these that is probably more something for Jeopardy question than anything else, but it’s kind of neat. There is a system to how these drugs get their crazy names.
But daratumumab targets another protein on the cell surface called CD38. And kind of the same idea, CD38 is a protein that’s abundantly expressed on myeloma cells and can serve as a target for daratumumab. And the same thing happens, the daratumumab sticks to the surface of the myeloma cells and serves as the flag for the immune system to recruit these killer cells to come get rid of the tumor.
One of the differences though, one of the very provocative difference between elo and dara is that dara by itself, just the act of dara sticking to myeloma cells can cause them to die. So that’s been seen in the results of single agent trials of daratumumab where just the antibody alone has led to clinical responses in a fraction of patients. That’s why I think there’s a lot of excitement around dara in particular is that by itself it has activity without needing to give it with Revlimid or Velcade or even with a steroid, even with dexamethasone.
Jenny: And that’s exciting because it could be potentially much better in combination then once you add it to other things, right?
Dr. Don Benson: Correct. And so dara is another drug — in my opinion anyway — that can’t get here soon enough. There are trial results that are published with dara in the New England Journal and good journals. The company has an expanded access program available now and they’re anticipating — I believe they’re anticipating potential approval in the first quarter of 2016. It’s another drug that I think is really kind of literally changed the landscape substantially for people that have myeloma when it comes out.
Jenny: Can I ask you some questions about the expanded access program? I know some patients who are anticipating some of these like elotuzumab or daratumumab and see them very close to being approved by the FDA and then available in the clinic. They want to get these early. So can you explain what an expanded access program is and then how do patients join these programs or when are they appropriate.
Dr. Don Benson: So this is a great question, especially today in myeloma and cancer in general because there are so many things coming. There are so many things that have promise but are not approved yet and are in that grey area where there’s been documented evidence of efficacy in early trials, but all of the rigorous testing and safety evaluations and follow-up hasn’t been completed yet.
One strategy to meet acute needs, to meet the needs of people right away, is what they call EAP or expanded access programs. Generally, this is a way for a company to provide access to a promising drug that’s not yet FDA-approved but still do it in an orderly manner and still do it in a way that would not only potentially benefit the folks who are getting early access to it, but also potentially aid the speed with which the drug is approved and available to everybody.
So daratumumab has an expanded access program. There is, I think, something like 50 sites around the country that are participating in it. From what I’m aware of, the sites were chosen geographically to try to give the most exposure to the most people. And there’s a very specific list of eligibility criteria for it. In other words, someone who has just been diagnosed wouldn’t be able to go and get daratumumab as expanded access. The reason for that is there’s a lot of good treatment options already out there.
But for example, to be eligible for the expanded access, a patient would have already had to have either Revlimid or Pomalyst. They already had to have Velcade or carfilzomib. I think there’s also a limit on the number of lines of therapy somebody must have had before they’re eligible.
There are some exceptions. If somebody truly has refractory disease and is truly in a difficult situation, there’s language in the protocol to allow access for people who are in dire need. But it’s a way that I think is good for everybody. It’s good for patients, it’s good for regulators and it’s good for the company too because they can set aside resources so they actually have drug available. I mean you have to kind of stop and think practically that if they’re going to give access to 500 people around the country, they better have the drug made, for instance.
Dr. Don Benson: But anyway, that’s active and enrolling now. There’s an expanded access program for elotuzumab as well, by the way. That’s open, I think, around 25 sites around the country if I’m not mistaken along the same principles saying hey, we have a drug that we think is promising. We have a drug with a new mechanism of action, a new class of drugs, a new approach. We think it’s going to be approved. We think it’s going to help improve people’s lives but it’s not quite there yet, and here’s a way that people can get it and know that drug is there and know that they may not only be helping themselves but helping get the drug out to everybody.
Jenny: And I think we’ll have to write a post on that on the Myeloma Crowd site about how you go about that expanded access program or how you apply for that because I think that’s fascinating for patients.
Dr. Don Benson: You know, Jenny, it’s interesting because all of this is out there and I’m sure it’s in areas where people can find it, but you have to know what to look for. For instance, if you go to the website clinicaltrials.gov and type in elotuzumab, you can eventually find the expanded access program and the emails and the contact numbers and the study sites. But if you don’t know clinicaltrials.gov you’re not going to find it.
Jenny: Yeah. It’s not the easiest program. You can find it, but it’s not the easiest.
Dr. Don Benson: They’re out there. You just need to know a little bit as to where to look. If you just type in expanded access you might get 2 million hits.
Jenny: Right. And then as a doctor, when these multiple different types of antibodies come out, how do you decide or determine which patient should get which one? Is it just the presence? Do you measure the presence of the cells and say gosh, you have more CD38 or you have more CS1, somebody has one over the other? Or how would patients kind of raise their hands and say, “I want to do elotuzumab,” or “I want to do daratumumab”?
Dr. Don Benson: Yes, that’s a great question and this is exhilarating because this is finally where the field is. We talked about this two years ago that not all myelomas are the same, and that’s gotten traction that there’s not one kind of myeloma.
So the new idea that I think is going in parallel with all of these immune therapies is that not all immune systems are the same either. So in parallel, as we discover different types of myeloma, we also need to work on trying to figure out differences in patient’s immune systems to match, to truly personalize immune-based therapies literally on an individual basis because there are patients for whom daratumumab will not work and elotuzumab may work great and vice versa. We already have actually anecdotal evidence in patients who have been on clinical trials with one or the other and it’s worked and it’s quit working, and they went on a trial and got the other one and that one has worked.
They’re not mutually exclusive either, so somebody could get benefit from elo for a while and then get benefit from dara or vice versa.
Jenny: And would you ever use them together?
Dr. Don Benson: We have a trial here. To my knowledge it’s the first combinatorial antibody trial where we’re giving elotuzumab with either lirilumab or urelumab, and so before I get too tongue-tied with all of these things
Jenny: Yeah, I don’t want to try to repeat that.
Dr. Don Benson: I’ll tell you the concept behind it. It’s a really provocative concept. So elotuzumab is a drug, is an antibody that sticks to CS1 on the myeloma cells and serves as a target. Lirilumab and urelumab are antibodies that stick to immune cells. And lirilumab is one that we worked on at Ohio State for a decade, and it’s a drug that’s meant to release the brakes from the natural killer cells. It’s a disinhibiting drug that blocks inhibitory receptors on myeloma cells. So half of the patients in this trial get elo and liri together. The other half of the patients get elo with the drug called urelumab, and urelumab is an antibody that functions to augment an immune response. So in other words, once the killer cell is turned on, urelumab is like a turbo charger. It accelerates or it augments their cytotoxic potential.
So the purpose of the study is to ask this scientific question. Which one is better? Is it better to release the brakes or is it better to step on the gas? It’s a bit of an oversimplification, but I think it’s the answer to your question. We’re actually doing these combinatorial antibody studies now in the clinic with patients.
Jenny: Does that study include Revlimid or you’re testing it by itself with these other two things to see if they can work by themselves?
Dr. Don Benson: Right, just by themselves, so no Revlimid, and also guess what, no dexamethasone.
Jenny: Oh, yay! I bet lots of patients would be jumping up and down about that. Yes.
Dr. Don Benson: So that’s really exciting because if you think about combining dara and elo, I think it will be a cool study. The concern is that they’re both tumor targeting and so theoretically could you run the risk of confusing the immune system by giving it two targets at the same time? Or conversely, would it work even better since you’re planting two flags on the same cell?
It’s probably inevitable that trials like that are going to get done. The trial we’re doing with our antibodies is a complementary trial where one antibody sticks to the tumor and one sticks to the immune cell, and can you bring the dance partners together by influencing them both independently?
Jenny: Fantastic. Well, is there anything else you want to cover on monoclonal antibodies before we move on?
Dr. Don Benson: There’s a couple really quickly. There’s one called isatuximab that we should just mention briefly. Isatuximab is also a CD38 antibody similar to dara. It’s a little earlier in its development, but I think down the road it’s going to be a promising drug.
The reason I wanted to bring it up though is to demonstrate that point that you talked about earlier, how do you decide who gets what? With isatuximab, we’ve been participating in its development here at OSU as well as dara and elo. But with isatuximab, we had some data at ASH last year that I think is really where this field needs to go, and so what we did, we have a phase I study, phase Ib study where 31 patients got Revlimid, dexamethasone and isatuximab, and we saw overall something like two-thirds of the patients had a response and some of them were really durable responses and some of them only lasted a few months. So what happened was we looked at all of the proteins on the immune cells that determine self from non-self; in other words, how can the immune cells tell what is their own and what’s foreign, and did genotyping on all of those and looked at the relationships between what is self on tumor cells and what is self on the immune system.
We identified the relationship between KIR, between these inhibitory receptors and self-molecules on the tumor cells, and if the patient had that dyad expressed, if they had that relationship expressed, the chances of responding to isatuximab were over 90%. So if you look at the people with the most durable remissions, they all had this relationship in their immune system.
Now, if they didn’t have that relationship, their chances of responding to isatuximab is only 50% or 56%. I forgot the exact number, but it was half what it was if they had it. And so I think that’s where our field in immune therapy needs to starts heading. I think that FISH and genetics and mutations and tumor biology is critical, we know that already. But in parallel, we have to learn about the immune system, and one day down the road you could conceive of someone the same way that they have gene expression profiling or they have cytogenetics or FISH done, they have an immune panels done, and from that information we can say, “Yes, you need isatuximab or you need daratumumab or you need nivolumab or you need indatuximab,” based not only on their unique myeloma but on their unique immune features. So I wanted to mention isa because of that piece of data.
Jenny: That’s fascinating, and a follow-up question, two follow-up questions. So I know SAR was a CD38. Is that now isatuximab or that something different?
Dr. Don Benson: That’s the same drug.
Jenny: Okay, so I knew the old name but not the new name.
Dr. Don Benson: Yes, isatuximab is formerly known as SAR 650984.
Jenny: Okay. I don’t remember the numbers ever. I remember SAR something.
So in terms of the measurements, how do you measure immune system response? Like what test would you get to try to look to learn that? Because that to me, I’m a huge advocate in understanding the genetics of your disease and everything that you need to be able to request drugs personally or at least know your condition so you can make educated choices about your care. So if there’s something else that we need to know about the immune system, then that would be one more thing to request of your doctor maybe.
Dr. Don Benson: Yes, I think at least on the laboratory side of things we look at the phenotype of the cells, in other words, what proteins are being expressed on the surface of the different immune cell subsets, and then we look at their function too, what are they capable of doing, in a test tube. This adds another layer of complexity to immune therapy for myeloma because we know just the presence of myeloma can affect how the immune system works.
Myeloma cells make cytokines, for example, that can disregulate the immune system, that can suppress the immune system. So there may be windows of opportunity in somebody’s treatment regimen where an immune therapy would work beautifully, and then other windows of opportunity where it may not work at all. Some of that is from the disease and then honestly some of that is from treatment too.
We know for example dexamethasone is profoundly immune-suppressive. We actually just published a combinatorial immune therapy a few days ago where we intentionally had no dexamethasone in the protocol at all. We have another combination immune therapy here that’s open now that intentionally left out dexamethasone because we don’t want to shoot ourselves in the foot with an effective combination that may be attenuated with a steroid on board.
I’m sorry, I don’t know if that answered you question or not.
Jenny: Yes, I think so.
Dr. Don Benson: But it’s something more complicated than just blood counts. I think that’s important. You can’t say, oh, somebody’s white count is 6000; therefore it will work; or somebody’s lymphocyte count is a thousand; therefore, it will work. It’s much more complicated than that.
I think that when have lab meetings here with my group, one of the things we often talk about is these subtle differences in the immune system and how they could be manifest on a day-to-day basis. You could envision these subtle differences being inherited on a bell-shaped curve just like everything else. On one end of the curve are these really striking immune deficiencies, these people who are born with severe immune defects and get sick at an early age and often die from infections as children or young adults. We know that’s true, that chronic granulomatous disease, there is a variety of immunodeficiencies that are heritable.
And since we know that, one of the things we talk about in the lab all the time is that there must be another tail on that bell shaped curve. There must be people on the other end who through whatever means inherited an especially potent immune system and what can we learn from those people that we can take into cancer therapy, what can we learn from those mutations and those single nucleotide polymorphisms that we could take into a therapeutic realm.
I think its overly simplistic to say if your white count is five you can get X, Y or Z, but there’s something deeper about the function and not only that, where somebody is in their treatment and what treatments they have had already and how active their disease is and so on.
Jenny: Well, it just goes to show that you really need to have a myeloma specialist in your corner, I believe, because I don’t a general oncologist can know all the nuances of this regardless. Very few people are even getting genetically tested, and that was available several years ago. So now you’re adding more and different and very cool things to increase your chances of getting a more personalized treatment and you really have to either be your own advocate or find somebody who really knows what they’re doing.
Dr. Don Benson: I think another good example is PD-1. This programmed death receptor 1 is a huge, huge development in immune therapy for cancer and solid tumors and melanoma. Targeting PD-1 on immune cells has been really just an explosion in cancer research and translation.
Jenny: Well, maybe you can explain what that is and how it works for people who aren’t familiar with it.
Dr. Don Benson: Yes, so it’s very interesting. So this whole class of drugs are drugs that target immune cells. They don’t target cancers cells. They actually target proteins on immune cells. And they’re all meant to disinhibit. So we talked about one already. Lirilumab hits inhibitory KIR.
There’s another one. The godfather of this whole realm is a drug called ipilimumab or Yervoy which targets CTLA4. And then there are at least four drugs in clinical trials now for myeloma that target PD-1 or programmed death receptor 1.
PD-1 is an important protein. It keeps your immune system from getting out of control. In the normal setting, if somebody gets an infection or a virus or what have you, PD-1 is a very strong checkpoint to keep you immune system under control so things don’t spin out of control when your immune system is dealing with that infection.
The interesting thing, in 2010, over five years ago, we published that myeloma cells express the ligand for PD-1, and other groups have done this too. It’s not something we did alone.
But what they do basically is capitalize on a normal immune checkpoint as means to evade immunity so that the cancer can continue to grow. So nivolumab and pembrolizumab are two drugs that are already FDA approved in other indications that are being tested to target PD-1 now in myeloma. There’s another one that was previously called pidilizumab, it’s called MDV9300 now. We have that one in a clinical trial here at Ohio State.
The interesting thing with all of these is that by disinhibiting the immune system, you can effect an immune response. You can activate the immune system not by stimulating it but by taking the brakes off. There are other drugs too that target the ligand as well on the tumor cells themselves.
But the interesting thing with this approach is that the hope is that not only is it going to clear the cancer, it’s going to lead to a tumor response but it’s going to lead to the immune system gaining an ability to keep the cancer from ever coming back again. For example, with MDV9300, in the early mouse models of that drug, they would have a mouse, they would give the mouse cancer, they would treat it with this drug, the cancer would go away, and then when they try to give cancer back to the mouse again, they couldn’t do it. The mouse wouldn’t get that cancer again.
So the promise of these disinhibiting antibodies is not only that they’ll help to clear the cancer but then they’ll keep the immune system in a surveillance mode to keep it from ever coming back.
Jenny: That would be amazing. And these are also considered in the monoclonal antibody group that mentioned before. They’re just a different kind, right?
Dr. Don Benson: Correct, these are all different kind of antibodies. So one way to keep them all straight, anything that ends with mab is an antibody. Anything that has a T in it, like indatuximab or rituximab, those are antibodies that are directed against tumors. T is for tumors. And then, any antibody that ends in mab that has an L in it is directed against the lymphocyte or an immune cell, so lirilumab, urelumab, ipilimumab, nivolumab, those are all directed against immune targets.
Jenny: That’s great. Okay. Well that makes sense. And how far along are these compared to like daratumumab?
Dr. Don Benson: Yes, I would say there have been data presented and published with these, although I would say they’re sort of in the second tier, they’re still in the earlier stages of development. They’re being given — like in our study, we’re doing it with Revlimid, but no steroid. There are other studies that have done in with Rev/dex for example or for example in combination with a tumor vaccine.
So there’s single agent data out there, there’s combinatorial data out there but it’s not yet ready, I think, for a big phase III study. It’s coming and it’s inevitable, Jenny. It’s going to happen. It’s just not there yet.
Jenny: And then, hypothetically, I mean further along of course, but you could use this together with — you could use the other monoclonal antibodies for targeting the cancer cells. You could use this one to target the immune cells. Those would be two totally separate targets, right?
Dr. Don Benson: Correct. Or you could envision using one — one of the pieces of conventional wisdom out there is that immune therapies might work better earlier in the disease course because the immune system hasn’t been beaten up yet. It hasn’t been exposed cytotoxics and a lot of steroid and radiation and hasn’t been exposed to myeloma for a long time. So one argument about immune therapy is that they should be given early in the disease course when the immune system might still be resembling a normal immune system.
The correlary to that though is that myeloma evolves over time. We’ve talked before, you and I, about subclones and dominants and how different clones can rise over time and there may be clones that achieve dominance that express PD-L1 and they would prime time for a PD-1 antibody, whereas, others might express abundant MHC and be prime targets for an inhibitory KIR antibody.
So I think that at least an appreciation for the moving target is important when we’re getting to a point to decide on personalizing immune therapies at least with antibodies.
Jenny: And how do you check for PD-1 expression? Where do you find that?
Dr. Don Benson: You can do it several ways. On the lymphocytes themselves you can see it by flow cytometry. You can do it by Western blot as well. For PD-L1, for the ligand on the tumor cells, there’s been a little bit of difficulty in getting a really good grade diagnostic antibody for it, although there’s some out now that you can use for flow cytometry or Western blot. It’s a question you have to ask though. It’s not one that is run routinely on a typical flow panel. It’s something that’s done on a research basis.
Jenny: And so these PD-1 are more in the phase I/phase II kind of stage?
Dr. Don Benson: Exactly.
Jenny: Or just phase I?
Dr. Don Benson: Well, our study is a phase II here.
Dr. Don Benson: But yes, phase I and phase II generally.
Jenny: So they’re both. Do you want to go to the next category? Or is there anything else?
Dr. Don Benson: Yes, we should talk about the CAR cells really quickly because the was just published last week in the New England Journal. And because you guys are funding CAR cell research, this is really important and really exciting.
Jenny: We are!
Dr. Don Benson: CAR cells are exciting because they take the patient’s own immune cells and basically, through genetic modification, teach those immune cells how to kill myeloma cells. They do it by expressing a receptor for a protein on the surface of the myeloma cells, and then they expand these cells in Petri dishes in the laboratory and then infuse them back into the patient, and then the CAR cells or the CART cells, sometimes people call them CART, will go in and eradicate the tumor.
And CAR cells, this whole technology has exploded in the last few years after really dramatic results in different forms of leukemia in both in adults and children. And now there is literally dozens of CAR cells that are being developed for all kinds of different cancers from brain tumors to pancreatic cancer to breast cancer to blood cancers to myeloma.
And just last week in the New England Journal of Medicine, there was a paper published using CART19 cell to treat somebody with multiple myeloma, and these data were also presented at ASCO a few months ago at the big annual meeting.
The patient who is described in the New England Journal paper was a young patient with IgA myeloma who had everything in the kitchen cupboard basically, and they took her to a second autologous transplant and then 12 days later gave her an infusion of CART19 cells. And that was all done over a year ago, and she’s still on a strict complete remission today.
It’s a really cool study for a lot of reasons, not the least of which is her outcome. That’s the coolest one I think, in my opinion. A close second though is how it worked because myeloma cells don’t have the target on them that this CAR cell is directed against them. So this is where it gets really interesting.
Jenny: That’s surprising.
Dr. Don Benson: Yes. The CAR cell that they used is a CD19 CAR cell. And so CD19 is a protein that’s on various B cells, but it’s generally not expressed on myeloma cells. So the fact that it would work at all in myeloma is very provocative, but it did. It clearly worked for this patient. I think for six or seven of the ten who were in the trial, this approach seemed to work despite the target not being on the tumor cell.
Jenny: And why do you think that is?
Dr. Don Benson: Well, there are a couple of explanations. The one that I would like to believe the most is that CD19 is on myeloma stem cells and the CAR cell eradicated her stem cell population and may have cured her disease. There are other explanations that maybe by eradicating other CD19 bearing cells it made the environment inhospitable for the myeloma cells and so they went away. There’s a bunch of other potential explanations to explain the finding, but I think the most interesting one that what we hope is true is that they’ve identified a way immunologically to clear the stem cell niche, the tumor stem cell niche that may be CD19-positive.
So anyway, in the paper it’s really fascinating because unlike other CAR cell trials, she did not have a big infusion reaction, she did not have a lot of toxicities when the cells were given, she tolerated it just fine, and then interestingly the cells persisted for a while and then they went away, whereas in other patients who have been through CAR cells with leukemia they find these cells persisting for a long time in their bloodstream.
Not only that, in this patient, in the New England Journal paper, she eventually recovered CD19 B cells in her bloodstream. So the cells didn’t recklessly kill everything that had CD19 on them, or if they did, the good ones grew back and the bad ones didn’t. So it’s really an interesting publication for a variety of reasons, but I think that you could tie all of those together under this hypothesis that they may have identified a way to eradicate a myeloma stem cell niche with a CAR cell, with an immune approach.
Jenny: That is huge. That is so huge.
Dr. Benson: It’s really cool. It is. It’s really cool. September 10th it was published in the New England Journal, so the timing of our call is awesome.
We have a CAR cell here at Ohio State that is targeting CS1. There’s actually several around the world that targets CS1. There are CAR cells that are being developed for BCMA, for B cell maturation antigen. There was one at the NIH. For example, there are CARs at other institutions that use different receptors and different genetic technology. There’s a CAR for kappa light chain that’s in trials. So I think this whole field is breathtaking with the pace that it’s taken off and really with these sorts of results that we’re seeing.
This is part and parcel of an immune therapy too. It’s very important to say in a forum like this that traditionally, even 20 years ago when I was a student doing immune therapy research that the traditional knock on immune therapy is that the response rates aren’t high, that only 15% or 20% of the patients in trials may respond to immune treatment, and that goes back 30 years in some of the earliest immune therapy studies.
The reason we keep after it is that when patients respond they have durable responses so it’s a phenomenon where it may not work for everybody, and that gets to that idea we’ve talked about all on the call that different tumors, different immune systems. But when it works, it tends to produce a durable response. It tends to produce a very long lasting durable non-relapse survival, which we hope is a cure.
Jenny: Well, maybe we can talk about timing then. I know you mentioned it earlier and the timing might be important where you have these windows of opportunity. What do you see as the most opportune windows of opportunity for applying either the CART cells or the monoclonal antibodies or even the vaccines?
Dr. Don Benson: I think with present day standards of care, I think that the one window that’s most attractive to me at least is in the early period after an autograft, and there are a couple of reasons for that. The first reason is that you’ve cleared out as much myeloma as you can with the tools that we have, so people in the early post-transplant period will hopefully have the least amount of myeloma in their body that they’ll ever have. It’s been maximally suppressed.
And in parallel, people in the early post-transplant period have, you could say, hit the reset switch on their immune system. They have a period of time there where it’s their own immune system, but it’s been redeveloped from the infused autologous stem cells. And these early recovering cells, particularly natural killer cells, even though they’re young, are capable of killing. They’re capable of recognizing tumor and capable of killing tumor.
So I think that at least on the near horizon that the early post-transplant period maybe the most advantageous window. So to point in that CAR cell trial that was published last week, they took this patient to a second autologous transplant before they gave her the CAR cells.
Tumor vaccine, actually, Dr. Borrello’s work that you’re funding too with tumor-infiltrating lymphocytes, I think that’s also in the post-transplant content if I’m not mistaken.
Jenny: Yes, it is. He wants to use the body’s natural ability where you’re regrowing all those lymphocytes as like a double whammy.
Dr. Don Benson: That makes eminent sense to me. That’s really a very opportune time to intervene with immune-based therapies.
Jenny: And how about for people in an existing remission period? I know that won’t happen for early stuff when you’re doing these studies and things because you’re trying to test for safety and effectivity and things like that, but I think people who are in remission but think that it’s probable that the disease is going to come back, I mean it mostly does, is there something that they can do while they don’t have a big tumor burden that’s nontoxic? That would be very appealing, I think.
Dr. Don Benson: I couldn’t agree more, yes. There are trials going on with immune-based therapies for maintenance. So our dual antibody trial that I mentioned earlier has a cohort for post-transplant maintenance for example. Those are situations where, again, the disease has been maximally suppressed. The immune system is at least healthier if not back to health and can you bring a therapy with minimal if any side effects to act not on the tumor but on the immune system to augment the police force, to keep surveillance and keep things in check. So those are active trials. Those are ongoing trials right now.
Jenny: That will be great. And with all this, I don’t know if you want to talk about anything else specifically, but I have some general questions for you. So any other treatment categories you want to talk about before I ask a general questions and I’ll open it up for our caller questions?
Dr. Don Benson: No, let’s keep going.
Jenny: So I guess we kind of covered this a little bit, but how does a doctor decide what to give a patient? And how does the patient choose a clinical trial to participate in? Because it’s so overwhelming. I have several friends who are contemplating which trials do I join right now, and some of it is which trial can I qualify for? But you feel like you’re playing roulette sort of with your health.
Dr. Don Benson: Yes. We talked about this a little bit when we talked about clinical trial participation a couple of years ago. But I think the most important thing is that you need an effective relationship with your provider, and that could be with your physician or it could be with the physician’s nurse practitioner, or it could be with — somebody could get care from a local community setting and have a collaboration with an expert or someone who specifically focuses in myeloma. The setup doesn’t matter, but you need that visceral gut sense relationship between who is taking care of you and what decisions are being made. That’s number one.
Beyond that, I think it depends on where somebody is in their disease history and what kind of myeloma they have. We talked a little bit about the differences between phase I, phase II, and phase III in the past. A lot of phase I trials, even some of the ones I mentioned today, people get a standard of care with a new drug already. So virtually all trials today don’t use placebos or sugar pills anymore. It’s not like you’re going to get in the trial and not get treatment, unless the standard of care is no treatment.
But most trials today are trials where there’s an effective combination already in place and they’re adding an experimental agent to it. So I think that goes back to point number one to be able to say, “Is this right for me right now?” to somebody that you trust and someone who knows your situation intimately frankly.
I think it’s important to say being in a trial you’re going to help everybody else who comes after you, you’re going to help the people in the waiting room and you’re going to help the people who walk in five years from now. But the optimal solution or the optimal outcome is yes, you’re going to help everybody else but you’re going to help yourself too. And with the thousands of trials that are out there right now, I think you need that relationship with your caregiver and potentially more than one, potentially also an advocate who can just be there to bounce ideas off of and say, “Hey, did you consider this or that?”
And then it comes for the practical aspect too of what is somebody willing to do. I’ve had patients who go to North Carolina to be in a trial or I’ve had patients move from other states to Columbus to be in a trial here, like sell their house and buy a house here and move here. Obviously everybody can’t do that, but I think finding the right trial starts with finding the right doctor and somebody who’s willing to say, “I don’t have it but this doctor does over here and I’ll call him for or I’ll call her for you, and you can go over there.”
Jenny: Yes, I think that’s ideal, and I think sometimes it’s rare. I think patients need to have enough knowledge that they trust the doctor but that they can ask intelligent questions as well because you can really maximize the time with your doctor if you yourself are up to speed. And I know a lot of people are trying to do that more so.
Dr. Don Benson: I tell my patients at Ohio State the trials are here for you; you’re not here for the trials. It’s sort of semantic, but it’s not, that the trials are here for patients to participate in them. They can easily go to other places and get very good standards of care from very good doctors, but our trials are here for you. In other words, on the same thought or maybe the other side of that coin is you’re not here just to get a number assigned to you and get a treatment to fill a spot on the study. It’s actually quite the opposite that if we believe a trial is right for you, we’re going to bend over backwards to make that happen, not only for everybody’s benefit but for your benefit.
And I think, Jenny, that most doctors in myeloma feel the same way.
Jenny: Well, I agree.
Dr. Don Benson: I think there’s something about that the community. Yes.
Jenny: It’s a community that is very collaborative, Ive found. They enjoy working together, they like sharing their research and their findings, and they are willing to recommend that you go to see other people if they don’t have what you provide. So I agree.
It leads me to a follow-up question. It just seems like the trick maybe in all these different combinations. So you go through the standard study process where you have the phase I, the phase II, phase III, it gets approved and then how do you maybe speed up this process to know which combinations are going to be the most effective when there are so many more options available? So it’s a blessing and then it’s a challenge at the same time. How do you get through that quickly?
Dr. Don Benson: Yes. I think the easy answer is science. I think that we talked about this too that it’s a blessing that there are so many things in development and there’s so much work going on. But the consequence of that is we don’t have ten years to do a trial and see if that makes people live longer. We need to know sooner than that. You could argue we don’t have two years to see if something makes people live longer, and so trials use other end points like response rate, so out of a hundred people how many people respond to this drug. Or they use remission time or progression-free survival as a surrogate end point for overall survival.
Most of the time these days those things correlate but not necessarily. Just because a drug works for 86% of people doesn’t necessarily mean it’s going to work for the next patient in the waiting room. I think that what I meant by the science always wins is that we need earlier methods to determine effectiveness, and that’s based in science and it’s based in mechanism of action and it’s based in understanding. In immune therapy, it’s based on understanding the relationship between the tumor and the immune system.
In that way we’ll evolve hopefully out of our current phase I, II, III criterion where it’s toxicity and safety and then efficacy, and then it’s about what we have to let’s identify 30 patients where these drug is going to work over 90% of the time and test it. Damn, it worked. Okay. Now, let’s submit for our approval. And yes, you’re going to have a limited label. You’re not going to be able to give it to everybody, but you’re going to be able to give it to people who have an extraordinary chance of it working and then a good chance of it being a durable and effective therapy for them.
Dr. Don Benson: That my soapbox.
Jenny: I like your soapbox. I think faster is better for everyone and I know you have to be cautious about how you do it and go through the process and make sure it’s safe and everything, but faster is always better for people who feel like the clock is ticking.
So my last question will be — maybe it’s not a fair question because it’s like who is your favorite child kind of question — but out of these different strategies or approaches or combinations, which do you see as being potentially curative or the most exciting or promising to you?
Dr. Don Benson: I think that it is not fair because I got a dog in this fight. But actually, I think that the right answer is that if an immune therapy is going to be curative it has to eradicate this notion of a myeloma stem cell clone. It’s a little controversial in how you define that, what it might look like or whether there may be more than one even, whether they’re subclones that cause relapses or drive disease at different points in time. But I think that a curative therapy is one that eradicates that tumor propagating clone or that stem cell niche that people talked about for a while and then they didn’t talk about for a while and now it’s coming back into interest again.
I think the CAR-19 paper that’s in the New England Journal last week is a great example of that. If that’s true that’s how it worked, that gives us a lot of insight as to where we should be going and what we should be targeting with immune-based treatment. Whether that’s with the CAR cell or whether it’s with an antibody or vaccine, it’s unclear to me. I don’t know that I could pick a favorite out of everything we have.
If CD38 for example is expressed by the myeloma stem cells, then dara and isa would be great to integrate into that somehow. But I think conceptually, that’s probably the next step on the horizon is how do we get to that clone of cells that was responsible for all that’s happening and how do we get rid of those.
Jenny: And maybe part of the answer that you just said was it depends. It depends on your immune system and your kind of disease. So maybe that’s just going to depend.
Dr. Don Benson: The lessons are there, the principles are there, the examples are there. You could go even to — I mean it’s controversial to say – but you can go to the realm of allogeneic transplant and say, yes, there’s people who’ve had donor transplants whose myeloma went away and it never come back. It’s certainly not a standard of care, it’s certainly not risk-free, but could you at least ask the question, are there people who have a type of myeloma that’s appropriate for that approach where the risk benefit is mitigated and that might be a curative potential for a fraction of patients.
Are there other subtypes where it’s going to take an antibody or it’s going to take a CAR cell or it’s going to take combinatorial chemotherapy and an autograft with radiation and have a tumor vaccine? Yeah, there are probably subtypes like that too.
Jenny: Okay, great. Well, Dr. Benson, I want to give an opportunity to patients who are calling in to ask a question of you. So if have a question for Dr. Benson, you can call 347-637-2631 and press 1 on your keypad.
While we wait for people to do that I would like to ask a question from a smoldering patient who just said, “How does this all apply to the smolderers?”
Dr. Don Benson: So that’s a great question. Actually, we have a clinical trial here now using daratumumab for people with high-risk smoldering myeloma. I think that there’s a lot of interest right now in using immune-based therapies for people with smoldering myeloma for the same reasons that maybe you can catch the horse before it gets out of the barn. Maybe that’s a setting where the immune system still has some abilities that are lost when the disease becomes active.
So we have a trial with daratumumab. I believe there are trials of elotuzumab as well in a smoldering setting. There have been studies done with the KIR antibody, the inhibitory KIR antibody in the smoldering setting. So that’s a very active area of research actually in immune-based treatment.
Jenny: Well, that’s good to know. And then the vaccine, those are the monoclonal antibodies, right? But in terms of the CAR T-cell stuff or the vaccines, is there any option for them?
Dr. Don Benson: Not that I’m aware of. There was a paper that was published in Blood a few years ago using an NKT cell approach in smoldering myeloma, I believe from the group at Yale where they gave an alpha-Galactosylceramide protein that worked a bit like a vaccine, I guess, to treat people with smoldering myeloma. I think CAR cells are considered too risky for the smoldering setting now. The risks that are involved with the CAR T-cell infusions and side effects and the potential toxicities of CAR T-cells have kept them out of the smoldering setting, at least for the time being, at least until we learn more about what the right target is and the right dose of CAR T-cells is and how frequent people should get them and so on.
Jenny: Great. I had another email question for Pat and he was wondering is for the compassionate use program, do they use the same type of exclusion criteria that they do for clinical trials? Like he’s a nonsecretor, so sometimes he has a hard time getting into clinical trials. Is it the same for the compassionate use or does that not matter?
Dr. Don Benson: It depends. This is a little subtle, but it’s important. The expanded access programs are the not the same as compassionate use programs. They are a sort of in their intent, which is to get a promising drug that’s not already approved to somebody who needs it. A compassionate use program and expanded access program have that intention shared. An expanded access program is a little more structured though in that they do have criteria that have to be met for somebody to be eligible to be in the expanded access program. Usually those are for the patient’s own safety as well as for their own benefit too. We talked a little bit about the criteria for daras study for example.
Compassionate use is a little bit different because an expanded access program is a formal program where the company has drug in hand, they’ve got approval from the regulators to do the study to make the drug available. Compassionate use is more of a one-off. It’s more of an attempt by a patient or a caregiver or a loved one to get a drug that’s not approved to an individual patient, and that process can be very different from an expanded access program.
It’s interesting we were talking before we went on the air about this. There’s actually one company now that’s set up an independent bioethics panel of folks to determine eligibility for their compassionate use program, and it’s, to my knowledge, the first one in the whole industry, the first one in the whole area to do this. It was set up back in April or May of this year to give guidance when patients do come and ask for compassionate use for one of their experimental products.
It’s a board of folks who — obviously some physicians are on there, but it’s led by a bioethicist. It’s not led by somebody from the company or somebody with a vested interest in the drug or the disease or what have you. It’ led by someone whose background is in ethics.
It’s a really interesting approach because it is an understatement to say that it is a difficult situation. But increasingly now, and I think this is a good thing, I think patients are taking control and becoming self-advocates and becoming collective advocates and demanding more speed and more success and all of that is good. But at the same time, if you have two people who are out of options and may benefit from experimental treatment and one of them has a twitter account and one doesn’t, the person who has social media gets 500,000 likes and can take that to a TV show and they can generate a whole lot of disproportionate interest in their cause when the other person might be left behind.
It’s difficult to look at these without kind of a lifeboat ethic them. At least to me, everybody’s life is important. You can sort of leave all the religious and spiritual dimensions out of it if you like and just say, “Well, your life is important because there’s never going to be another Jenny Ahlstrom. You’re unique, so you’re important. And everyone else is too.”
So when it comes down to compassionate use for drugs, that needs to be honored. It seems the way to operationalize that is with ethicists involved and with people involved who are not from the company or from the regulators but from somewhere else.
Jenny: That makes sense.
I’m going to leave you the last word. We have a lot of listeners, but they’re all shy about asking you a question. So I would like to just leave you the last word and if you want to make a comment about just joining clinical trials in general.
Dr. Don Benson: Yes. I think that just to re-emphasize that point that at least in the United States, less than 5% of people with cancer ever participate in a clinical trial. All of the drugs we have today: Revlimid, Pomalyst, Carfilzomib, even thalidomide, even melphalan, even dexamethasone, those are standards of care from people who went into clinical trials before us. And all the ones we talked about today, daratumumab and elotuzumab and CAR T-cells and isatuximab and lirilumab and all of these other drugs are coming because of clinical trials.
So, one of the big rate limiting steps towards a cure is getting these trials done. I think it’s important, for me, for other doctors who might be listening that we not mistake activity with accomplishment, that clinical trial participation is important but participating in the right trial is important.
I think that’s my parting thought or my parting message is to really take the time to find a provider who’s interested in this and interested in you and make it a win-win for not only your own healthcare but everybody else who’s in this with us together.
Jenny: Well, we are just so grateful for all that you’re doing. We’re thankful that you both treat patients and that you’re doing research to really move the bar in these really unique and effective ways. So thank you for all you do every day for us.
Dr. Don Benson: Well, thank you Jenny. I’m grateful for you and all you do.
Jenny: Well, we’re very happy you’re in this field, thinking about myeloma every day.
Dr. Benson, please keep us updated on all that you’re doing. We look forward to seeing your papers at ASH in December as they come out. We’ll be sharing those on the Myeloma Crowd website. If there’s anything that patients can do for you, let us know. We would be happy to do it.
Dr. Don Benson: Very good. We hope we have some really exciting stuff at ASH. We’ll have hopefully some PD-1 data there and we’ll hopefully have some basic science data on how the immune system and myeloma cells interact together. So I’ll let you know.
Jenny: Okay, great. Well, thank you so much.
Thank you for listening to this episode of Innovation in Myeloma on Myeloma Crowd Radio. You can join us next time for our next interview as we learn more about how we as patients can help drive to a cure for myeloma by joining clinical trials.