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Diagnosed With CLL? Start Here

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Diagnosed with CLL? Start Here from Patient Empowerment Network on Vimeo.

What do newly diagnosed chronic lymphocytic leukemia (CLL) patients need to know? Expert Dr. Ryan Jacobs explains how CLL occurs and provides an overview of treatment types. 

Dr. Ryan Jacobs is a hematologist/oncologist specializing in Chronic Lymphocytic Leukemia from Levine Cancer Institute. Learn more about Dr. Jacobs.

Download Resource Guide   |  Descargar Guía en Español

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Transcript:

Lisa Hatfield:

There’s a lot going on in terms of novel therapies and new options. But before we jump into all of that, the tool box that’s expanding, can you introduce CLL and provide an explanation of what it is and what that means for a newly diagnosed patient?

Dr. Ryan Jacobs:

So chronic lymphocytic leukemia, or CLL, is the most common chronic lymphoma/leukemia. It is really both most of the time. It presents with what we call lymphocytosis, meaning the white blood cell count, and specifically the lymphocyte count is high or elevated. To call it CLL, to make that formal cancer diagnosis, we can generally take a patient’s blood sample and put it through a fancy machine that we call a flow cytometer, that looks for characteristic markers on the outside of the cells, and if there’s a bunch of those cells, we call that a monomorphic population.

So a bunch of those cells that look the same, and they’re B cells, that’s the type of lymphocyte count they are, and they’re over this threshold of 5,000. Then that is the diagnosis right there, we don’t need an invasive procedure. You generally do not need a bone marrow biopsy or a lymph node biopsy. There is in about 15 percent of cases, the disease presents with just in large nymph nodes, and the white count is normal. We call that small lymphocytic lymphoma. It’s considered an overlap with CLL, and I’ve had many patients that have started off with SLL and then eventually manifest elevated lymphocyte count later in their disease course. So it is considered an overlap, the treatment is the same for both of those disease entities.

So that’s the diagnosis of CLL and how it generally shows up initially. In a nutshell, it’s a cancer of the aging population, average age is 70. I have a lot of patients that ask me, “Why did I get CLL?” And the answer is, “We don’t know.” It’s that way with most cancers, unfortunately, we don’t know why one person gets a cancer and the other person doesn’t.

But it obviously has something to do with the aging effect on the DNA of the B lymphocytes because of how much more common it is as patients get older. 

Lisa Hatfield:

We know that therapies are evolving faster, hopefully faster than patients are relapsing, which is a good thing. So when they do relapse, chances are there will be a new option for this patient. But a CLL cure still remains elusive.

So, Dr. Jacobs, if you can speak to…we’ll just jump right into some of the newer, the novel therapies and things that are being investigated with CLL treatment. If you can just speak to some of those newer therapies, the novel pathways and targets that are currently under investigation with CLL, we’d appreciate that.

Dr. Ryan Jacobs:

Sure. We’ve come a long way in how we are managing this common cancer that’s benefiting a lot of patients. And as mentioned, with this cancer being one that is more common in the older population, we do know that the population of the United States specifically is getting older, there’s going to be more 70-year-olds. So these breakthroughs are helping a growing number of CLL patients.

Before 2014, really outside of a clinical trial, the only way we could treat CLL Is with combinations of chemotherapy and an immune therapy, like a monoclonal antibody called rituximab (Rituxan), that was kind of our first, what we would call targeted treatment outside of chemotherapy that we had, and it was, like targeted treatments are, well tolerated. It was an antibody that targets B cells specifically.

So we were combining it with chemo, we would call that chemoimmunotherapy, and it helped a lot of CLL patients. But for many, those were poor prognostic markers in particular, and those with relapse disease, chemotherapy was not very helpful, and it was quite toxic in many circumstances.

So we’ve been fortunate that since 2014, we’ve had a lot of new treatment options, and they’re targeted therapies. It’s not like non-specific cytotoxic chemotherapy, these are treatments that have been developed with specific targets in mind that are unique to the B-cell neoplasm, the B-cell cancer, the CLL. And the first of these that really changed everything was a BTK inhibitor called ibrutinib (Imbruvica), that we got in 2014.

Initially, we can only use it in the relapse setting, but eventually, in 2016, we could start treating patients as a first line of therapy with ibrutinib.  And then in 2019, we had a newer version of BTK inhibitor, we call those second-generation BTK inhibitors. That drug was acalabrutinib. And it eventually was shown in a head-to-head study to be just as effective as ibrutinib in a relapsed patient population, but it had less side effects than ibrutinib. So in, specifically, atrial fibrillation, hypertension. Cardiac toxicities overall were one that they really focused on in that study.

So as a whole, when we were choosing BTK inhibitors, we were shifting away from ibrutinib, shifting to acalabrutinib, and then just as…earlier this year, we had a third BTK inhibitor, zanubrutinib (Brukinsa), that was approved. It’s also considered a second generation BTK inhibitor like ibrutinib and acalabrutinib (Calquence). It treats CLL in the same way, in how it inhibits BTK or Bruton’s tyrosine kinase, that’s over expressed in CLL cells.

But it also has a favorable toxicity profile when compared head to head with ibrutinib, and now we have two second-generation options between acalabrutinib and zanubrutinib. And it’s not really easy for us to know between those two, which is “better.” When we decide to treat with a BTK inhibitor, we’re usually choosing between those two at this point, and we’re trying to personalize the decision for the patient, and there are some different factors they can get involved in that complicated decision.

Luckily, we are not limited to BTK as a target. I mentioned earlier, we have monoclonal antibody, rituximab like the one I mentioned, but a newer version of rituximab, a more potent version, obinutuzumab. Is one that we have available along with a Bcl-2 inhibitor, venetoclax (Venclexta). That is now, as of 2018, improved in the frontline CLL setting, also approved in the relapsed setting, of course, since 2016.  And we use venetoclax with a monoclonal antibody like obinutuzumab (Gazyva), and together they are a very potent combination that cause pretty rapid cancer cell death, as opposed to the BTK inhibitors that more put the cancer to sleep and require daily dosing indefinitely for as long as the drugs work.

And remarkably, the data on BTK inhibitors tells us that should work for many, many years. They’ve been following some of the patients that got treatment in the first line setting, and eight years out, there’s still more than 50 percent of the patients are free of progression, so they can’t even quote an average response time yet. With eight years of follow-up on the early ibrutinib patients.  The difference with venetoclax combined with a monoclonal antibody like obinutuzumab, is because it causes a more rapid cell death, you can give it on a time-defined schedule. So we tend to give it for one year in the first-line setting and two years in the relapse setting, and the antibody portion is just given for the first six months. 

The BTK inhibitors and venetoclax are oral treatments, so that’s a big win for patients to avoid the infusion center for those treatments, but the IV antibody treatments will still require some trips to the infusion center if you’re doing that combination with venetoclax. For most patients, those two targets are what we’re choosing between, and we try to personalize the decision to the patient. And again, that’s a very complicated discussion on what is “best.” And we use things like the prognostic work-up, medical problems that the patients already have, medicines that patients are on, to help make the best treatment decision for our CLL patients. But those…for in terms of how well that treats the CLL, both of those are considered equivalent options for the large majority of CLL patients.

We’ve got some things on the horizon, but in general, those are two targets that we have at this point. There is for relapsed patients, PI3 kinase inhibitors that are still FDA-approved at this time, that aren’t quite as effective and more toxic, so we sometimes think about using one of those targeted therapies if a patient has already progressed on a BTK inhibitor in venetoclax class. In the future, we are looking towards combining BTK and Bcl-2 inhibitor. Like, for example, there’s been studies already done that I’ve put many patients on, with ibrutinib-venetoclax, and I believe there’s a question about that later.

There’s also an ongoing study that I have opened at my institution that’s looking at acalabrutinib and venetoclax. So taking these two pills together in a time-defined manner, so you don’t have to take the BTK inhibitor indefinitely. And then there are some therapies that have already been improved in other lymphomas, and we wonder if they’re going to have a role in CLL eventually. So we now have bispecific antibodies, so that’s taking a drug like rituximab or obinutuzumab and adding a T-cell engager to it, so it has two targets or it’s bispecific.

And we have that drug, mosunetuzumab (Lunsumio) available in follicular lymphoma and there’s several others in development, and we’ll see how their role comes into play in CLL as well. As well as CAR T-cell therapy, where we take a patient’s T cells and genetically engineer them to attack the cancer. That’s now an approved therapy for many different kinds of lymphomas and multiple myeloma as well.

So we wonder if that’s going to have a role in CLL. But I think for the foreseeable future, it’s going to be looking first at BTK and then Bcl-2 inhibition, or vice versa. And we don’t really know which is better to go first, we think they’re both…they can both be sequenced one after the other. And then maybe it will have some of these other breakthroughs coming in and helping for after patients need something beyond those therapies.

And there’s probably going to be a lot of patients that never need anything beyond those options, those initial couple of targets, because they do so well. I think in the most immediate future, the approval that is going to give us a new great option is going to be for an alternative site BTK inhibitor, or it’s also called a non-covalent BTK inhibitor.

And there’s this drug called pirtobrutinib (Jaypirca), it has been approved in mantle cell lymphoma and likely will get approved in CLL this year. And that drug specifically is a BTK inhibitor that still works even in patients that have, say, progressed on ibrutinib or acalabrutinib or zanubrutinib. That will be a new target available for CLL patients and probably pretty quickly become one of the go-to drugs that we use for relapsed CLL patients that have already been treated with a BTK…with a traditional BTK inhibitor. So growing number of options and it’s really great for our CLL patients. 

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CLL Patient Expert Q&A: Start Here

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CLL Patient Expert Q&A: Start Here from Patient Empowerment Network on Vimeo.

The START HERE program bridges the CLL expert and patient voice, whether you are newly diagnosed, in active treatment or in watch and wait. In this webinar, Empowerment lead Lisa Hatfield and expert Dr. Ryan Jacobs  provide an overview of the latest in CLL, managing CLL side effects and options for CLL progression.

Dr. Ryan Jacobs is a hematologist/oncologist specializing in Chronic Lymphocytic Leukemia from Levine Cancer Institute. Learn more about Dr. Jacobs.

Download Resource Guide   |  Descargar Guía en Español

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Transcript:

Lisa Hatfield:  

Hello and welcome. My name is Lisa Hatfield, your host for this Patient Empowerment Network program. In this important dialogue, we bridge the expert and patient voice 

to enable you and me to feel comfortable asking questions of our healthcare teams with more precision. The world is complicated, as is a cancer diagnosis, but understanding your CLL doesn’t have to be. The goal is to create actionable pathways for getting the most out of CLL treatment and survivorship. Joining me today is Dr. Ryan Jacobs, a CLL expert from Levine Cancer Institute. Thank you very much for joining us today, Dr. Jacobs, we really appreciate you being here and your time and expertise.

Dr. Ryan Jacobs:

Thanks for having me, Lisa.

Lisa Hatifield:

Before we get started, please remember to download the program resource guide via the QR code. There is great information there that will be useful during this program and after. Okay, let’s get started. So, Dr. Jacobs, I’d like to talk about what’s on the chronic lymphocytic leukemia radar, and rather than saying that entire phrase each time, I’m going to refer to it as CLL, because I’m pretty sure I’ll fumble that up. There’s a lot going on in terms of novel therapies and new options, but before we jump into all of that, the tool box that’s expanding, can you introduce CLL and provide an explanation of what it is and what that means for a newly diagnosed patient?

Dr. Ryan Jacobs: 

So chronic lymphocytic leukemia, or CLL, is the most common chronic lymphoma/leukemia. It is really both most of the time. It presents with what we call lymphocytosis, meaning the white blood cell count, and specifically the lymphocyte count is high or elevated. To call it CLL, to make that formal cancer diagnosis, we can generally take a patient’s blood sample and put it through a fancy machine that we call a flow cytometer, that looks for characteristic markers on the outside of the cells, and if there’s a bunch of those cells, we call that a monomorphic population.

So a bunch of those cells that look the same, and they’re B cells, that’s the type of lymphocyte count they are, and they’re over this threshold of 5,000. Then that is the diagnosis right there, we don’t need an invasive procedure. You generally do not need a bone marrow biopsy or a lymph node biopsy. There is in about 15 percent of cases, the disease presents with just in large nymph nodes and the white count is normal. We call that small lymphocytic lymphoma. It’s considered an overlap with CLL, and I’ve had many patients that have started off with SLL and then eventually manifest elevated lymphocyte count later in their disease course. So it is considered an overlap, the treatment is the same for both of those disease entities.So that’s the diagnosis of CLL and how it generally shows up initially. In a nutshell, it’s a cancer of the aging population, average age is 70. I have a lot of patients that ask me, “Why did I get CLL?” And the answer is, we don’t know. It’s that way with most cancers, unfortunately, we don’t know why one person gets a cancer and the other person doesn’t. But it obviously has something to do with the aging effect on the DNA of the B lymphocytes because of how much more common it is as patients get older.

Lisa Hatifield:

Thank you for that overview, Dr. Jacobs. We do have CLL patients who are watching this who are newly diagnosed, they may be in active treatment, they may be in remission, they may be managing their CLL just fine right now in their lives. So we’re along the whole spectrum of CLL, so thank you for that overview. We know that therapies are evolving faster, hopefully faster than patients are relapsing, which is a good thing. So when they do relapse, chances are there will be a new option for this patient. But a CLL cure still remains elusive. So, Dr. Jacobs, if you can speak to…we’ll just jump right into some of the newer, the novel therapies and things that are being investigated with CLL treatment. If you can just speak to some of those newer therapies, the novel pathways and targets that are currently under investigation with CLL, we’d appreciate that.

Dr. Ryan Jacobs:

Sure. We’ve come a long way in how we are managing this common cancer that’s benefiting a lot of patients. And as mentioned, with this cancer being one that is more common in the older population, we do know that the population of the United States specifically is getting older, there’s going to be more 70-year-olds. So these breakthroughs are helping a growing number of CLL patients.

Before 2014, really outside of a clinical trial, the only way we could treat CLL Is with combinations of chemotherapy and an immune therapy, like a monoclonal antibody called Rituximab, that was kind of our first, what we would call targeted treatment outside of chemotherapy that we had, and it was, like targeted treatments are, well tolerated.  It was an antibody that targets B cells specifically. So we were combining it with chemo, we would call that chemoimmunotherapy, and it helped a lot of CLL patients. But for many, those were poor prognostic markers in particular, and those with relapse disease, chemotherapy was not very helpful, and it was quite toxic in many circumstances. So we’ve been fortunate that since 2014, we’ve had a lot of new treatment options, and they’re targeted therapies. It’s not like non-specific cytotoxic chemotherapy, these are treatments that have been developed with specific targets in mind that are unique to the B-cell neoplasm, the B cell cancer, the CLL.

And the first of these that really changed everything was a BTK inhibitor called ibrutinib, that we got in 2014. Initially, we can only use it in the relapse setting, but eventually, in 2016, we could start treating patients as a first line of therapy with ibrutinib (Imbruvica). And then in 2019, we had a newer version of BTK inhibitor, we call those second-generation BTK inhibitors. That drug was acalabrutinib (Calquence). And it eventually was shown in a head-to-head study to be just as effective as ibrutinib in a relapsed patient population, but it had less side effects than ibrutinib. So in specifically, atrial fibrillation, hypertension. Cardiac toxicities overall were one that they really focused on in that study. So as a whole, when we were choosing BTK inhibitors, we were shifting away from ibrutinib, shifting to acalabrutinib, and then just as…earlier this year, we had a third BTK inhibitor, zanubrutinib (Brukinsa), that was approved. It’s also considered a second-generation BTK inhibitor like ibrutinib and acalabrutinib.

It treats CLL in the same way, in how it inhibits BTK or Bruton’s tyrosine kinase, that’s overexpressed in CLL cells. But it also has a favorable toxicity profile when compared head to head with ibrutinib, and now we have two second generation options between a acalabrutinib and zanubrutinib. And it’s not really easy for us to know between those two, which is “better.” When we decide to treat with a BTK inhibitor, we’re usually choosing between those two at this point, and we’re trying to personalize the decision for the patient, and there’s some different factors they can get involved in that complicated decision. Luckily, we are not limited to BTK as a target. I mentioned earlier, we have monoclonal antibody, rituximab (Rituxan) like the one I mentioned, but a newer version of Rituximab, a more potent version, obinutuzumab (Gazyva). Is one that we have available along with a Bcl-2 inhibitor, venetoclax. That is now, as of 2018, improved in the frontline CLL setting, also approved in the relapse setting, of course, since 2016.

And we use venetoclax with a monoclonal antibody like obinutuzumab, and together they are a very potent combination that cause pretty rapid cancer cell death, as opposed to the BTK inhibitors that more put the cancer to sleep and require daily dosing indefinitely for as long as the drugs work. And remarkably, the data on BTK inhibitors tells us that should work for many, many years. They’ve been following some of the patients that got treatment in the first line setting, and eight years out, there’s still more than 50 percent of the patients are free of progression, so they can’t even quote an average response time yet. With eight years of follow-up on the early ibrutinib patients. The difference with venetoclax combined with a monoclonal antibody like obinutuzumab, is because it causes a more rapid cell death, you can give it on a time-defined schedule. So we tend to give it for one year in the first-line setting and two years in the relapse setting, and the antibody portion is just given for the first six months.

The BTK inhibitors and venetoclax are oral treatments, so that’s a big win for patients to avoid the infusion center for those treatments, but the IV antibody treatments will still require some trips to the infusion center if you’re doing that combination with venetoclax. For most patients, those two targets are what we’re choosing between, and we try to personalize the decision to the patient. And again, that’s a very complicated discussion on what is “best”. And we use things like the prognostic work-up, medical problems that the patients already have, medicines that patients are on, to help make the best treatment decision for our CLL patients. But those…for in terms of how well that treats the CLL, both of those are considered equivalent options for the large majority of CLL patients. We’ve got some things on the horizon, but in general, those are two targets that we have at this point. There is for relapsed patients, PI3 kinase inhibitors that are still FDA approved at this time, that aren’t quite as effective and more toxic, so we sometimes think about using one of those targeted therapies if a patient has already progressed on a BTK inhibitor in venetoclax class.

In the future, we are looking towards combining BTK and Bcl-2 inhibitor. Like for example, there’s been studies already done that I’ve put many patients on, with ibrutinib-venetoclax, and I believe there’s a question about that later. There’s also an ongoing study that I have opened at my institution that’s looking at acalabrutinib and venetoclax. So taking these two pills together in a time-defined manner, so you don’t have to take the BTK inhibitor indefinitely. And then there’s some therapies that have already been improved in other lymphomas, and we wonder if they’re going to have a role in CLL eventually. So we now have bispecific antibodies, so that’s taking a drug like Rituximab or obinutuzumab and adding a T-cell engager to it so it has two targets or it’s bispecific. And we have that drug, mosunetuzumab (Lunsumio) available in follicular lymphoma, and there are several others in development, and we’ll see how their role comes into play in CLL as well. As well as CAR T-cell therapy, where we take a patient’s T cells and genetically engineer them to attack the cancer. That’s now an approved therapy for many different kinds of lymphomas and multiple myeloma as well. So we wonder if that’s going to have a role in CLL.

But I think for the foreseeable future, it’s going to be looking first at BTK and then Bcl-2 inhibition, or vice versa. And we don’t really know which is better to go first, we think they’re both…they can both be sequenced one after the other. And then maybe it will have some of these other breakthroughs coming in and helping for after patients need something beyond those therapies. And there’s probably going to be a lot of patients that never need anything beyond those options, those initial couple of targets, because they do so well. I think in the most immediate future, the approval that is going to give us a new great option is going to be for an alternative site BTK inhibitor, or it’s also called a non-covalent BTK inhibitor.

And there’s this drug called pirtobrutinib, it has been approved in mantle cell lymphoma and likely will get approved in CLL this year. And that drug specifically is a BTK inhibitor that still works even in patients that have, say, progressed on ibrutinib or acalabrutinib or zanubrutinib. That will be a new target available for CLL patients and probably pretty quickly become one of the go-to drugs that we use for relapsed CLL patients that have already been treated with a BTK…with a traditional BTK inhibitor. So growing number of options and it’s really great for our CLL patients.

Lisa Hatfield:

Thank you for that overview again, Dr. Jacobs. It does sound like there are a lot of new therapies coming out, especially for relapsed patients, super exciting for them. And this is actually a great time to jump right into questions. We have many questions from patients that different patients have submitted. But first, I want to remind everybody that this program is not a substitute for medical care. Please consult with your medical team for advice on your own condition or disease. And, Dr. Jacob, I was taking notes as you were talking, because you had spoken a little bit about a combination of the BTK inhibitor and Bcl-2 inhibitor with venetoclax. And I did a little research last night before I talked with you, and it sounds like that is something that the CAPTIVATE trial is investigating. 

So that’s exciting, and a patient asked about that, what that trial is. And it’s music to my ears as a cancer patient to hear something like “fixed duration,” it’s also investigating a fixed duration so patients and have maybe a bit of a medication vacation. So can you speak to that trial a little bit and explain what it is a little bit on how that might benefit patients with CLL?

Dr. Ryan Jacobs:

Yeah. So one of the best elements of treating with venetoclax is that it produces a deep level of remission in many patients. In fact, when given with the monoclonal antibody obinutuzumab, to CLL patients receiving that treatment as a first line of therapy for their CLL, about three-quarters of CLL patients will get to so deep of a remission that we call them minimal residual disease-negative. And that’s a blood test or a bone marrow test, but more easily done as a blood test, where we can look to a sensitivity of one in 10,000 white cells and determine if there’s any CLL in those 10,000 cells. We can actually go deeper than that, but we say, we call patients negative if they’re less than one in 10,000. And so 75 percent of patients will get to that depth of remission just with obinutuzumab for six months along with venetoclax for a year. So when researchers saw that, they recognized that we could probably stop treatment in those patients getting venetoclax because venetoclax yields these deep responses. And then the next kind of thought was, well, could we give a BTK inhibitor with venetoclax, but also over a defined treatment timeline and maybe get some of the remarkable benefits of treating with a BTK inhibitor but not get stuck being on therapy for years and years.

So the CAPTIVATE study was the first really to, in a large Phase II manner, look at that combination in a younger patient population, it was for patients 70 and younger. And it wasn’t in a high risk or anything, it was all comers. But they did have to be 70 and younger and getting treatment as a first-line therapy. So the combination was very effective. As of the last American Society of Hematology meeting in December, four years of data was reported and a large percentage of patients were still free of progression, over 80 percent still free of progression. And that’s three years off therapy at that point.

It was well-tolerated, not many patients had to come off due to toxicity. It was, in fact, less than 10 percent had really significant toxicities requiring discontinuation. So it was a well-tolerated effective treatment.

I do have one of those studies to open at my institution, the acalabrutinib-venetoclax combination, it’s called the MAJIC trial, and it is a large Phase III study that if it’s successful, I think would lead to the approval of giving those two drugs together. But then the extra credit question is, who should get the combination and who should get the drugs separately? And we don’t have an answer for that right now, and that’s a long topic of debate among CLL specialists.

Lisa Hatfield:

Great. Well, thank you. So for that trial you spoke of that you’re conducting right now, is that…is it only relapsed patients who are eligible for that? Or is that for front-line therapy?

Dr. Ryan Jacobs:

No, this is a first-line therapy that the MAJIC study is.

Lisa Hatifield:

Oh good. That’s promising for patients too.

Dr. Ryan Jacobs:

And it has a really good comparator arm, so that won’t be a problem that the standard arm on that study is venetoclax plus obinutuzumab, so it’s comparing against one of our best treatments, and so we really will get the answer of does it look better to use the BTK with the Bcl-2? Or is it not really that much better than just giving an venetoclax with obinutuzumab? And then the one obvious element that I didn’t mention that would be nice for most patients in addition to being efficacious and well-tolerated is if you could get an all-oral combination. Of course, venetoclax with obinutuzumab, you’re still getting quite a few infusions with the obinutuzumab over the first six months. So that’s a lot of time in the infusion center that you could avoid with just the combination of two oral targeted agents. So that would be a breakthrough for patients too, I think.

Lisa Hatfield:

Well, you commented also on something that’s really important for patients to know, and that is that if you go into a clinical trial, you won’t be given nothing for cancer clinical trials, you’re going to be given the standard of care or whatever it’s being compared to. So for patients who are considering that.

Dr. Ryan Jacobs:

That’s a Phase III. Yeah, for Phase III. If you go on an earlier phase trial, you know exactly what you’re getting. There’s usually not any randomization for earlier phase studies, you just get the intended treatment.

Lisa Hatfield:

Okay, great. Well, thank you so much for explaining that. So we have some pretty specific questions, and we have a patient who wrote in and asked, “What is the difference between IGHV-mutated and IGHV-unmutated CLL? And can you talk about treatment considerations for those?”

Dr. Ryan Jacobs:

Yeah. So that’s part of a bigger discussion around the prognostic work-up of CLL and not all CLL is the same, and we’ve done a really good job of figuring out tests to separate out the CLL patients that tend to behave more aggressively and respond to certain kind of therapies, versus those that are more of what we call indolent or slow growing and respond to other kinds of therapies. I do want to say, I haven’t mentioned it yet, we still don’t treat CLL if it’s not causing any problems. And about half of patients get diagnosed as sort of an accident, and they get a blood test for something else, and their white count is elevated, and that leads to a diagnosis, but they feel fine. We still leave those patients alone. Even with these good treatment options we have, we recognize that there are a select percentage of CLL patients that don’t ever need treatment, and so we don’t just want to start treatment in everybody.

But I do still like to check this prognostic work-up, even if I’m not going to start treatment, but I make sure and ask the patient if that’s what…iIn line with what they want. But certainly, if you’re going to start treatment, you’re required by guidelines to check a prognostic work-up, and I would really encourage the CLL patients tuning in to ask their oncologist, “What is my prognostic work-up?” if they’re going to start treatment.  Because of the oncologists, unfortunately, that have to deal with lots of other cancers, maybe don’t always know the right test to send. I’m very spoiled in that I get to just treat lymphoma and specifically focus a lot of my research in CLL and get to stay up with all this. I don’t know how a general oncologist keeps up with everything, honestly.

But the big three tests are going to be the FISH analysis, fluorescence in situ hybridization. And then IGHV mutational analysis, and then also a TP53 mutation analysis. And I don’t really have time to go through all of those, but IGHV is the question I get a lot. “What is that?” It’s one of these rare findings where it’s actually normal to have a mutation at the IGHV. IGHV stands for immune globulin heavy chain variable region, and it is usually mutated in B lymphocytes because it’s part of the process of a mature lymphocyte that is able to make a lot of different kinds of antibodies. And it undergoes somatic hypermutation, is what it’s called, as the B cell matures. Generally in oncology, the more mature a cancer is, the less aggressive it behaves and usually the easier it is to manage, and that is the case with CLL. So think of an unmutated IGHV CLL cancer as a more primitive or a more immature cancer clone, and as such, it is harder to treat.

In about half of patients will be found to be unmuted at the IGHV and historically, all we had was chemo and we knew these patients weren’t going to respond for near as long as the IGHV-mutated patients were to chemo. What’s nice is, with our targeted treatments, particularly the long-term data with the BTK inhibitors, it doesn’t look like it matters whether you’re mutated or you’re unmutated. So that’s one of the really great things with our new treatments for CLL, is it has, the people that have benefited the most are the ones that were doing the worst, so that’s great. It’s not just the patients that were already doing well, that are doing even better.

Lisa Hatfield:

So I just want to take a step back and kind of looking at this through the lens of a newly diagnosed CLL patient. You’d mention that sometimes you don’t treat every CLL patient. So is there something, if you find a patient who does not need treatment, is there something you tell the patients as far as regular monitoring? Will you monitor them to see if it progresses to the point where it requires treatment?

Dr. Ryan Jacobs:

Yeah. And we’re fortunate that this is a blood cancer that most of the time we can follow with a simple blood count and follow the white count, follow how the…follow the health of the bone marrow by looking at things like anemia, low red cell count, or a low platelet count that we call thrombocytopenia. So that’s the easiest thing to follow, but I’m also talking with my patients and examining my patients. I want to know if their length nodes are causing them a lot of pain, because we should treat that, there’s no reason they should live in pain.I want to know if they’re waking up drenched in sweat all the time, if their quality of life has been really affected by that. Or are a dramatic amount of fatigue that we can’t explain by some other cause. And I also, of course, examine the nodes myself and make sure that there’s no alarming findings there. So that’s really what’s involved with checking on a CLL patient that’s on active surveillance, that’s what we call it. And there’s a list of criteria that the oncologist should know in terms of deeming who needs treatment and who doesn’t. And so we’re kind of following the same rules, so to speak, in terms of who gets treated for CLL.

Lisa Hatfield:

Okay, thank you. So we have a patient who asked a series of questions here, and I think you already…you spoke pretty well to the role of the BTK inhibitors in treating CLL. I’m going to kind of clump these together.  So I guess three questions. What treatments do you think are the most beneficial for patients whose CLL has relapsed? What are the poor prognostic indicators for CLL? And along the same lines, what are the high-risk genetic markers for CLL?

Dr. Ryan Jacobs:

It’s a little more complicated discussion in the first line setting because both are options. At this point in time, we haven’t been…at least those that are, I would say, staying up to date on the CLL data, we have not been using chemotherapy for a long time. So most of the relapsed patients will have seen either one of the BTK inhibitors or venetoclax. And so what we do in the second-line setting is just use the other option that they haven’t seen. The data tells us, when you look at what treatments are being prescribed, most patients are going on BTK inhibitors, and they have been around longer than venetoclax in general. So for a lot of patients, that relapsed treatment is going to be venetoclax. Because that has the best data in terms of treating patients that have progressed on a BTK inhibitor like ibrutinib or acalabrutinib or zanubrutinib.

In the near future, we’ll have pirtobrutinib (Jaypirca) and so maybe, maybe some will get that drug before venetoclax, and that’s probably okay. And so we’ll have that additional option. The complicated patients, and I’ve alluded to this, or what do we do after BTK and Bcl-2? What are we left with? I mentioned PI3 kinase, that’s not a great option. There’s still stem cell transplant out there for young patients that are running out of options. Clinical trial is really what I would like to emphasize there.  If you’re a patient that can get to a high volume referral cancer center with a CLL specialist, I would do that. If you have seen BTK inhibitor and venetoclax and are looking for other options.

Lisa Hatfield:  

Great, thank you. So the next question is actually a really good question, I think we can broaden it a little bit. But the question is, “How can I ask my doctor to make sure I am being tested for serum markers?” And more broadly, I think a lot of patients are a little bit nervous about asking questions of their doctor, because they don’t want to feel like they’re questioning their expertise or doubting them. So how in general can we ask our doctor questions if we hear something? Or how we approach our doctor with those types of questions?

Dr. Ryan Jacobs:

So I mentioned asking your doctor, “What’s my prognostic markers?” I think this is probably the easiest way to get that information. And your doctor should be checking those. The question comes up like, what are the “high-risk” markers? We talked about mutated versus unmutated. Thankfully, our novel treatments that doesn’t seem to matter. Same goes with…there’s on FISH there used to be, if you found three copies of chromosome 12, that’s called trisomy 12, that doesn’t seem to matter With our newer treatments. A deletion at chromosome 11, again, used to not do as well with chemo. Novel therapies…doesn’t seem to matter. The one that is still potentially affecting outcomes, even with our novel treatments, are chromosome 17 aberrations, which stately are rare in the initial diagnostic setting. That or a TP53. A deletion at 17p or TP53 mutation probably is only going to be around 10 percent of patients or so. And in the relapse setting though, that number goes up because of the more aggressive cancers emerge, we call that clonal evolution. So maybe in the 20-ish percent range. These patients, we tend to prioritize indefinite therapies first, because it seems like these patients do better if you keep treatment going, as opposed to interrupted therapies like venetoclax. And so we tend to treat those patients with a drug like acalabrutinib or zanubrutinib first and then think about the venetoclax later for those patients.

Lisa Hatfield:

Okay. Okay. And just to clarify, for patients too, I know that a lot of cancers, there are discussions about the 17 deletion, 17p, and then also the TP53 gene. So if I understand correctly, the TP53 gene is housed on chromosome number 17. So if that is missing, then that patient may be missing that gene, that is considered a tumor suppressor gene, which we want. Is that correct?

Dr. Ryan Jacobs:

Right. So it’s either missing, which is what we see on FISH with a deletion, or it can be mutated and that’s the next gen sequencing, and often it will be both in those patients.

We think with indefinite, there’s some really good data that was just released with zanubrutinib. When they looked at 17p-deleted patients, there’s some long-term follow-up with ibrutinib-treated 17p-deleted patients. With chemo these patients would only get about a year or so, but we’re getting maybe even close to normal outcomes with long-term BTK. But we do know if you just give them a year of venetoclax and obinutuzumab for six months and then stop, they do relapse quicker than the other patients. So they relapse after about four years. As opposed to with five years of follow-up with that first line venetoclax approach, there are 62 percent of patients are still free of progression.

Lisa Hatfield:

Oh wow, okay. Thanks for explaining that too. I know that that chromosome 17 and the TP53 gene, that’s talked about in a lot of different cancers and it often come up, “How are those connected?” So thanks for just describing that a bit. So this patient is asking, “For patients who may be eligible for BTK inhibitors, are there specific comorbidities that might contribute to adverse side effects?”

Dr. Ryan Jacobs:

Yeah, so we screen…all BTK inhibitors have some cardiac toxicity. They have been shown with the second-generation BTK inhibitors to have less cardiac toxicity than ibrutinib, specifically atrial fibrillation. So if you have atrial fibrillation, maybe that’s a reason why you might go on venetoclax first as opposed to a BTK inhibitor. But it’s not a contraindication to getting a BTK inhibitor if the atrial fibrillation is under good control.  Other cardiac risk factors would include difficult to control hypertension at baseline, or heart failure. These are all things that might make us think twice about using a BTK inhibitor as our first therapy, because venetoclax has no cardiac toxicities. The other thing to consider is BTK inhibitors all to a degree have, and I describe it to patients, like an aspirin-like effect on the platelets. They do interfere with the platelet binding, which so universally, patients will know to varying levels some easier bruising.

And if patients are on, because of say, they’ve had a heart attack in the past and they’re on aspirin at baseline, or what would even be more concerning if they were on a drug like Plavix because they’ve had a stent placed, that would be something that would really concern me and would definitely push me more towards venetoclax, that again, doesn’t have those anti-platelet interactions. Also, patients who are on blood thinners because of a history of blood clot or atrial fibrillation, there is the potential increased risk for bleeding and bruising there as well. None of these are absolute contraindications, they’re just all what goes into the blender, if you will, of putting lots of information in and coming up with the best treatment decision as personalized for the CLL patient. We’re blessed to have multiple options, but it does make it more of a challenge to find the “best” option.

Lisa Hatfield:

Yeah. Thank you for that. We have several questions from a couple of patients regarding side effects. So the question, “How long will my side effects of my CLL treatment last? And what can be done to reduce those?” And specifically, a patient is asking if there’s a connection with CLL and gastrointestinal issues?

Dr. Ryan Jacobs:

So all of the treatments, including venetoclax, the BTK inhibitors, will have diarrhea listed as a possible side effect. It’s usually low grade. But generally, I have found the gastrointestinal toxicities abate some over time. So if they are present earlier, if you’re able to stick with therapy, they do tend to get better. For the once daily meds, I encourage those patients to try to take the drug in the evening. The GI tract tends to be less active later in the day, and you can sleep off some of the potential gastrointestinal issues. So I’ve had success there. Sometimes we have to lower the dose to just find the best dose to help mitigate some of these. There’s the antidiarrheals that can help if you need them. Imodium. I had a patient I saw earlier this week that Imodium didn’t really work, but good old Pepto Bismol did the trick from time to time. So certainly though, if the gastrointestinal issues are significantly affecting quality of life, we need to come up with a new plan, whether that’s reducing the dose or changing to a different option. Specifically, what’s nice about the BTK inhibitors is they all have data that show if you’re having problems with one, you can switch to the other and likely not have the same problem occur. So that’s nice.

Lisa Hatfield:

Have you ever seen any uncharacteristic side effects several times in your practice? Anything really unique? I’m just curious about that.

Dr. Ryan Jacobs:

Yeah. There’s always the patients, they can have a more severe form of maybe, of a more common side effect, like the…we were talking about diarrhea, I’ve had a patient that actually had a difficult, with venetoclax, had difficulties with the stool incontinence. So that was kind of a severe form of that. It wasn’t so much diarrhea that was the problem. But we were able to ultimately mitigate that with a dose reduction. I would say the way, particularly if it’s an unusual side effect, the best thing to do is to take a break. If it’s a serious side effect that needs to be addressed and it’s affecting quality of life or causing problems, take a break from the treatment. If you take a week off these treatments, particularly venetoclax, taking breaks doesn’t matter. We like not to take long breaks with the BTK inhibitors. But if you take a week off, these drugs don’t have very long half-lives. So if the issue is not getting any better and you’ve been off of treatment for a week, it’s unlikely that that issue is coming from the treatment. So that’s a way I try to sort through some…particularly if they’re unusual side effects sometimes. And certainly, if we deem that the issue is connected to the treatment, I’ll usually try lowering the dose before just giving up.

Lisa Hatfield:

Okay. Thank you. A patient had asked, and I love this question because I often wonder myself when I get up in the morning, my bones are creaking and popping, “How do you know the difference between,” this patient’s talking about fatigue. How does a patient discern, “Well, this is fatigue from my cancer or my treatment,” versus just normal aging? Whether it’s fatigue or bruising or any side effect.

Dr. Ryan Jacobs:  

Yeah. Fatigue is a really…I had an attending physician when I was in my training that said, “Treating fatigue makes me fatigued.” But it’s hard. If it’s really the only problem the CLL patient is having, it can be. All those other problems I had mentioned earlier, the low red cells, the low platelets, the painful nodes, the night sweats, I with close to 100 percent certainty know I can fix those with treatment.Fatigue, I’m not as confident when that’s the only issue that a patient’s having. I try to differentiate between fatigue from other causes and old age, and specifically to CLL. 

They try to put it as a metric and say, if you’re having to spend half the day or more just lying around and you’re not able to do your normal activities of daily living, like that’s a severe level of fatigue and treatment should be considered.I’m looking for somewhat of a precipitous decline, not necessarily just kind of the gradual fatigue that you might more relate to aging. The problem with treating fatigue is you’ll look, if you look at the possible side effects of all of these medicines I talked about, fatigue will be a potential side effect.So you’re sometimes trading one problem and getting another, or maybe the fatigue does get better, but then the patient has some different side effect that’s even worse than the fatigue. So it’s hard to really help when fatigue’s the only issue. But certainly, I have helped some patients with fatigue. We don’t have a test that we can do to know for sure is the fatigue coming from the cancer, or is it coming from something else. 

Lisa Hatfield:

Great. Well, that wraps up our program for today. Thank you so much for joining us, Dr. Jacobs.  I am Lisa Hatfield from Patient Empowerment Network.

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Emerging AML Treatment Classes Showing Promise

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Emerging AML Treatment Classes Showing Promise from Patient Empowerment Network on Vimeo.

What therapies are in development for acute myeloid leukemia (AML)? Dr. Ann-Kathrin Eisfeld discusses the latest research for AML treatment, including menin inhibitors and CAR T-cell therapy.

Dr. Ann-Kathrin Eisfeld is Director of the Clara D. Bloomfield Center for Leukemia Outcomes Research at The Ohio State University and a member of the Leukemia Research Program at the OSUCCC – James. Learn more about Dr. Eisfeld.

See More From INSIST! AML

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Transcript:

Katherine Banwell:

Are there therapies in development that are showing promise for patients with AML? 

Dr. Eisfeld:

There are so many of those. It’s hard to count. And this makes me very happy. There are exciting and again, targeted drugs.  

Once drug class is called menin inhibitors, which we – which were just published that show high promise.  

And again, very difficult to treat several groups of patients who harbor chromosome changes in MLL genes in here. So, that is a very exciting option.  

And there’s very exciting treatments with respect to what you call antibodies – monoclonal antibodies that attacks the surface proteins that are being checked regularly. And one of those, for example, is called magrolimab. And that has even promise in these high-risk leukemias or adverse risk leukemias.  

And then we are not there yet, but I’m sure we will be in the not too near future. There are also multiple trials that are looking at what we call CAR-T cells. But patients might have heard about for lymphomas or acute lymphoblastic leukemias. AML is a little more tricky with respect to those. 

But we’ve seen pre-clinical studies that look really exciting. And I think it’s just going to be just a little more fine-tuning to make those easier, available, and more targeted for AML patients. And I’m very much looking forward to seeing those come more onto the market.     

Katherine Banwell:

You mentioned the new menin inhibitors. Who are they right for?  

Dr. Eisfeld:

We try to find out more, but definitely for patients that have been shown to be beneficial for patients who have chromosomal and rearrangements of the MLL gene or KMT2A gene. And there’s also good data on patients who have NPM1 mutations.  

Even though we know – and these are mutations who harbor this kind of genetic change – have now a plethora, which is a great, of treatment options. 

Because we know even conventional chemotherapy has been working decently well in them. We know that venetoclax also is supposed to work very well in them. But again, the data on the menin inhibitor with respect to NPM1 mutations is very exciting. 

AML Treatment Approaches | Factors That Impact Options

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AML Treatment Approaches | Factors That Impact Options from Patient Empowerment Network on Vimeo.

What factors are considered when choosing an AML treatment approach? Dr. Ann-Kathrin Eisfeld explains how shared decision-making comes into play when deciding on a therapy and reviews the options available to treat AML.

Dr. Ann-Kathrin Eisfeld is Director of the Clara D. Bloomfield Center for Leukemia Outcomes Research at The Ohio State University and a member of the Leukemia Research Program at the OSUCCC – James. Learn more about Dr. Eisfeld.

See More From INSIST! AML

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Transcript:

Katherine Banwell:

With all the new tools that are available, what other factors do you consider when working with an AML patient to choose a treatment approach for them?  

Dr. Eisfeld:

The most important aspects are what we call – and this is – I’m glad that you bring this question up because I feel you have to think of – and that was what we’ve been talking about – called disease-associated factors. This is everything in the leukemic cell. They – how does a leukemia looks like? How does the blast look like? What changes are there?  

That’s the biggest part of what I would call patient-associated factors: the patient age, the patient performance status, actually the patient. In every – because I think, sometimes, we forget about it. But we just look at all the molecular testing.  

But even if – for example, there would be a patient with a very good risk leukemia, where I think, “Oh, this leukemia should respond very well to an intensive chemotherapy.” 

If the patient cannot tolerate chemotherapy or – and I see it more often than I would wish for patients who are young who have a great performance status, but they just cannot – they – their family reasons. Small children sometimes – they just cannot be away for so long. This all comes into consideration. So, it’s really important because we all work together as a team. And the right treatment for the leukemia might not be the right treatment for the patient.  

And for most cases, however, I think, it will only work if one stands with a whole heart with both physicians, and patients, and family. Because it’s a long journey behind the care that’s being given. And so, this is a joint decision-making, and there are different options that can be done. Of course, I would not advise something where I would think there are no chances of success.  

And so, this has to be an open discussion. But this is – it’s very often a very tough treatment to communicate that and see what are the goals of each patient? That will be most important for treatment and decision-making.     

Katherine Banwell:

What types of AML treatment classes are currently available?  

Dr. Eisfeld:

This is a very good question. The most classic treatment class is intensive chemotherapy. This is just because people might have heard the names. It is called 3 + 7 or 7 + 3, which refers to one weeklong impatient chemotherapy treatment. But you get one chemotherapy for seven days. And the first three days, you get a second treatment as well.  

That’s why it’s called three in seven in here, but it’s a total of seven days. So, we have intensive chemotherapy. And there are different flavors of it. But this is usually the backbone. The second class is what I would call a targeted inhibitor. And here we can look at two different aspects. We have targeted inhibitors for a specific DNA mutation that are found. And specifically, one are called IDH or FLT3 mutations.  

And these are pill forms that I usually by now combined with a third drop class which is called hypomethylating agents. And I will go through in a moment.  

But these are pills that really only work in patients and carry that genetic change. They have very, very low toxicity and very high chances of working. So, that’s why this testing is so important to see if one is one of the 15 percent of AML patients carrying an IDH mutation – 15 percent isn’t low. And a similar rate carries a FLT3 mutation.  

And then there is also going to target inhibitors. That is targeted because it is against what I would call a pathway. The gene that is commonly activated in acute leukemia – and this is called BCL-2 and the drug is called venetoclax (Venclexta).  

This is now stormed through the acute myeloid leukemia world in just a few years ago and has been approved as a front-line treatment option for several patients, especially for those who are older. And we know that even patients who respond usually favorably to chemotherapy, some of those also respond well to venetoclax the Bcl-2 inhibitor. The benefit is that this treatment in many cases if it works, can be done as an outpatient in here and has very often lower complications.  

It is actually has so good results that I – sometimes it seems too easy. So, we actually advise patients to still try to get – the first time they get the treatment, do it at a center where it’s done more commonly. Because it sometimes – don’t underestimated the power of a pill. And it’s still a very, very powerful drug. So, doing it in a controlled setting – because if cancer cells break down, they break down and can create all sorts of trouble.  

So, that is really something – for several leukemias, it can be concerning. And again, now the treatment group would be called hypomethylating agents. The names are azacitidine (Vidaza) and decitabine (Dacogen). And they act in a very different way. They try to change the epigenetics like methylation patterns. And often, if it is an untargeted way of the tumor cells and they can be used alone.  

Or very often by now in combination with the targeted inhibitors that I was just mentioning. These are infusions that can be done either over five, seven, or 10 days depending on the combination treatment. And for patients, as I mentioned before, that don’t respond well to many other options to those patients with a complex karyotype. This is, for example, a scenario where patients can just receive this as their only therapy.          

Katherine Banwell:

What about stem cell transplant? You didn’t mention that.   

Dr. Eisfeld:

Yes. That would be the next one. So, stem cell transplant always comes as an option, which I would call as a maintenance therapy. Again, two aspects. We have two different end goals.  

First is get rid of some leukemia. Second is to make sure it stays away. And as soon as the leukemia is in complete remission, depending on the performance status – the agent. Again, in multiple different things. It’s not an easy decision. 

At that time, there has to be a conversation. And that always involves a leukemia physician and a transplant physician very often. These are different providers that goes for the risks and benefits. Where the question is if I only continue to do chemotherapy – because it’s never only once. You would always have to repeat your chemotherapy. What is the likelihood that the leukemia comes back, and does it outweigh the risks that comes with the stem cell or bone marrow transplant that comes in here. But for many leukemias, especially for young patients and for patients with higher risks, this is the only chance of a cure. That is the most curative and only curative attempt for many leukemia attempts.  

Katherine Banwell:

Where do clinical trials fit into the treatment plan? 

Dr. Eisfeld:

That is the absolute backbone. We always have to think about that. 

Everything – all the treatment options that I mentioned – have been clinical trials, just very, very short time – very few years ago. So, every patient that comes to a leukemia or a cancer center, clinical trials will be discussed if they’re available. Because they will provide a special opportunity to have even more fine-tuned treatments – either newer agents. And I think what is very important to mention is that all clinical trials that are available would give the option of the best standard of care.  

And then the hope that a patient wouldn’t be getting any of the best standard of care options that are approved. The hope is that the new agent or added agent in many cases would even do better.  

It’s also important that there’s a lot of additional monitoring during the trial. I think it can be seen in two ways as two parts of a coin. In one way, it may be additional visits to the hospital or additional blood draws that are necessary to be sure that the medications are safe, and that researchers and conditions can learn about it. But on the other hand, it also gives you this extra bit of being looked after and really getting checked in and out, making sure that all organs are functioning that everything is just going fine. And many patients appreciate this a lot. And they have this pair of extra eyes on them all the time.  

Katherine Banwell:

Dr. Eisfeld, what therapies are available for AML patients who relapse or don’t respond to initial therapy? And is this treatment approach different from those who are newly diagnosed?  

Dr. Eisfeld:

Most of the time, the treatments available at relapse are the same available at the first diagnosis. Just because we know now that, for example, if you have a molecular marker that, for example, is available, it would act with also relatively high chance of relapse upset. However, at relapse, the most important thing I personally would do is consider a clinical trial even stronger than in the first mindset. 

 Because it means that the leukemia outsmarted current treatments very often. So, usually what we would be doing is see if there is a targeted inhibitor or a cell mutation FLT3 or IDH, which I would personally always prefer to go in MLL rearrangement now for the new menin inhibitors where one would go with the same option as if it would have been their diagnosis. But if not to really consider clinical trials is a strong urge. 

Katherine Banwell:

Should patients or should relapsed patients undergo genetic testing again? Is it necessary?  

Dr. Eisfeld:

Yes. At any time. Yes. Because we know that the leukemia changes. And you just can think about it in the way is that the cells that are surviving treatment, they’ve become smart. There was so much poison. There was so much treatment put on them. 

And the ones that survive might have a quiet additional chromosome change as additional gene changes. And even if a genetic change has not been present at time of diagnosis, the reason the cell has survived might have been that it has now one of these changes that came up on a later time during treatment or while the cell is hiding somewhere to come back. 

Making Treatment Decisions | Understanding Common Myeloma Therapies

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Making Treatment Decisions | Understanding Common Myeloma Therapies from Patient Empowerment Network on Vimeo.

What are common myeloma therapies, and when are they used? Dr. Ashley Rosko outlines the factors that impact treatment decisions and reviews available therapies including stem cell transplant, proteasome inhibitors, immunomodulatory therapies, and monoclonal antibodies.

Dr. Ashley Rosko is Medical Director of the Oncogeriatric Program at the Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Rosko.

Download Resource Guide

See More From INSIST! Myeloma

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Transcript:

Katherine:

We know that multiple myeloma patients have a number of options and that many available therapies are used in combination. 

So, I’d like you to walk us through the options that are available. 

Dr. Rosko:

So, I’m going to start by how the best way that I can frame out when we talk about newly diagnosed versus patients when they have relapse. So, there are therapies that are available for patients that are FDA-approved when they are newly diagnosed with the cancer, and there are therapies that are approved only when a cancer has acted up again or relapsed. 

So, I’ll kind of frame it from patients who are newly diagnosed. And then, I also will talk more about relapsed therapies and what we’re able to offer to patients. So, in first, when we talk about treatment options, we frame treatment based on a couple things. So, one is, we talk extensively about the disease biology. So, that plays an important role in how we decide which treatment the patient should get. 

And then, the second part about how – I would probably say there’s about four main parts. And so, disease biology is one, and another thing has to do with the patient characteristics. In terms of the patient’s overall health prior to developing cancer, and also how the cancer has impacted their health in terms of everyday activities. Whether or not a person has really slowed down quickly, whether they’ve been in the hospital, and how it’s impacting their organs. Because that plays a role in terms of what we’re able to give patients.  

If a patient has advanced kidney failure, which can sometimes happen, or if you have to focus more on protecting their bones and if there’s concern about fractures and things like that. And then independent of patient characteristics in terms of overall health, the last part I talk to patients about is their own preferences. It’s a hard thing to talk about, shared decision-making in a cancer that most people have never heard about, but there is certainly – when we talk about options and there are, it’s important to talk about shared decision-making in terms of what’s most important to them and where they – and most patients will say, “Well, I just want the best medicine.”  

And I say to them, “Well, you know, we have lots of options, and that’s the best thing about it, but we also want to be cognizant of the real world, of giving best options,” and for example, Many of my patients – so, I’m at The Ohio State University, I’m here. And a lot of patients travel. I have a lot of older patients that I care for, and they’re very independent with travel. And I want to make sure that whatever therapies we’re getting for them, that we can do this in such a way that maintains their lifestyle.  

So, the beginning part of a treatment, it is broadly described as – when we talk about someone who was diagnosed with this, it’s this thing called induction. So, induction is when we give anywhere from two to four medications to be able to control their cancer and put it into remission. And we know that the cancer is in remission because, like we started out the conversation with Dr. Cottini, myeloma makes proteins. Oftentimes, it makes proteins, those proteins are not nutrition proteins but are cancer proteins that we can track in the blood. 

So, we can check them every month and to make sure that the patients are having a really good response, and as such, we’re able to define that they’re responding to their treatment. Because they have a beginning stage in induction, which they’re given treatment, and then the goal is to put patients put in remission.  

Depending on the overall health of the patient, a standard of care for most patients diagnosed with multiple myeloma is to undergo an autologous stem cell transplant. An autologous stem cell transplant is not a transplant in which you’re getting cells from your brother or sister and they’re being donated to you. They are your own stem cells. We get them out of you when your bone marrow is free of disease, and then we would admit you to the hospital for a more intensive therapy and give them back. 

That is often the standard of care for patients newly diagnosed with multiple myeloma, and it is recommended for most patients. Some patients get – I like to think of it as a stem cell transplant not at the time of their initial diagnosis, but later on at the time of relapse, or some patients are not candidates for a transplant or elect not to have a transplant. And all of these options are very personalized to the patient. It’s very hard to say that this is exactly what we do. 

Because it’s a strategy where it requires a lot of shared decision-making to make sure that we’re getting good disease control, good quality of life, and deep, deep remissions for our patients. So, then, if a patient gets a transplant, there’s a period of recovery, and then patients go on a pill most often, a maintenance pill that they stay on for indefinitely. 

Myeloma is also a cancer which has perpetual therapy. Very different than many other cancers, where there’s a beginning and an end, myeloma for the most part is perpetual therapy, where you get some form of therapy at higher dosages versus lower dosages over a period of time.   

So, I’m going to talk broadly about the classes of drugs that we have and how we use them to be able to define therapy. 

So, the first class of drugs are called proteasome inhibitors. Just like many other cancers, we use different types of drugs to be able to target different aspects of a cancer cell’s growth cycle.  

So, very similar to how we do other drugs, these are very specific to the cancer cell, and they’re very targeted. So, unlike some of our other kind of classic chemotherapies, many of these medicines that I’m going to talk about are very targeted at the cancer cells without causing too many other problems. 

So, proteasome inhibitors include drugs like bortezomib (Velcade), which is given as a shot, carfilzomib (Kyprolis), which is given as an IV, or ixazomib (Ninlaro), which is given as a pill. They have different indications, but they’re the same class of drugs.  

The next class of drugs is called immunomodulatory drugs, or iMiDs. This includes things like lenalidomide (Revlimid), pomalidomide (Pomalyst). Those are the most common, and then we sometimes use the drug that the original iMiD drug, which is called thalidomide (Contergan). 

These are all pills that patients take, and so that’s oftentimes very nice for patients to be able to provide therapy at home, very well-tolerated. The next class of drugs are called monoclonal antibodies. On a cancerous cell, there is a marker. 

And so, we use monoclonal antibodies to be able to target the marker on the cancer cell. What that means is very specific. To that cancer cell, so, the most common target is the CD38, that’s a marker on one of the cancer cells. And we use a drug called daratumumab (Darzalex), that can be given as an IV or a subcutaneous agent, or another drug called isatuximab (Sarclisa). We also have other markers on the plasma cell. There’s a marker called SLAMF7, which we have other drugs called elotuzumab (Empliciti), which is often used for patients more in the relapse setting. 

How Do Myeloma Test Results Influence Prognosis and Care?

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How Do Myeloma Test Results Influence Prognosis and Care? from Patient Empowerment Network on Vimeo.

Key testing is important for understanding myeloma, but how do results impact care and treatment? Myeloma experts Drs. Ashley Rosko and Francesco Cottini discuss how test results can affect care options and encourage patients to discuss results with their healthcare team.

Dr. Ashley Rosko is Medical Director of the Oncogeriatric Program at the Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Rosko.
 
Dr. Francesca Cottini is Assistant Professor in the Division of Hematology at the Ohio State University Comprehensive Cancer Center. Learn more about Dr. Cottini.

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Transcript:

Katherine:

Dr. Rosko, what do the results of these tests tell you about prognosis? 

Dr. Rosko:

Yeah, I think this is a really important question. And, in my experience, when we encounter a patient newly diagnosed with myeloma, it is like drinking from a firehose in terms of the amount of information that we are reviewing and the amount of information that we are discussing with the patient and with their family. And oftentimes, we talk about this piece of these cytogenetic abnormalities, and we talk about – but I really encourage your patients and anyone who is listening in today to really take a deeper dive. 

Because sometimes it’s helpful as, one, you’re navigating a new cancer diagnosis, but that’s challenging in and of itself. And then, two, talking about a cancer, multiple myeloma, that is – most people don’t know so much about multiple myeloma, unlike breast or colon or lung cancer, and so I really encourage patients and their caregivers. And a lot of times this happens, where we’ll go over all the cytogenetic abnormalities, we’ll talk about how it plays a role in their overall treatment trajectory, and their prognosis, but also good just to circle back and say. 

Settling into what this diagnosis is, oftentimes, people on first time treatment. And then even sometimes months or even years into their diagnosis, they stop and they come back and they say, “Can we talk about this FISH data?  

Can we talk about what changes that I had within the DNA? What does this mean?” And that’s not uncommon at all.  

So, I really feel like for many people that are on the call here today, I think it’s important to say it’s okay to go back to your physician and say, “I’m learning more about this, now that I’m more familiar with what this diagnosis is, can we talk about these FISH changes, or can we talk about the stage of my cancer?” Because I think it’s oftentimes an overwhelming period of time to have a new cancer diagnosis. And I also want to just give permission to everyone on the call that it’s okay to go back and ask questions, even if it’s been months or years.  

So, having high-risk mutation can upstage a cancer and in the absence of high-risk mutations can downstage a cancer. So, what that really means is saying, “These biologic changes that are happening in the cancer cells give a sense of what we anticipate that the trajectory is going to be when someone is diagnosed.” 

Now, it’s imperfect. I feel like cancer just generally is unpredictable, and there are many things that we try as clinicians. And especially with the experience that we have, to say, “This is what we anticipate the course will be like you, in terms of response, in terms of the cancer being quiet.” As you all know, multiple myeloma is not a curable cancer right now. And for all patients, when they’re diagnosed, they’re often able to get disease control and be able for that cancer to be put in remission. And we do focus on remission. 

I think that’s also something that I talk to my patients about. Even though we can’t cure it, we can certainly control it, and that’s a big part of what we do. So, when we get good disease control, we’ll talk more about next therapies, but that is how Dr. Cottini – Dr. Cottini is a wonderful scientific investigator and knows all of the latest and greatest when it comes to different mutations that are identified within cancer cells. We partner very closely with her in terms of  scientific investigation and how the mutations that were newly identified, too, play a role in terms of response to treatment, and how we’re able to best treat them. 

Katherine:

Thank you for that. Dr. Cottini, do you have anything to add as far as what type of questions patients should ask their healthcare team about test results?  

Dr. Cottini:

I mean, I think Dr. Rosko already pointed out the most important things. So, multiple myeloma is a rare disease, and it’s not as intuitive to understand as breast cancer, lung cancer, prostate cancer. 

So, it’s really important as a patient to understand which tests are we ordering. Why are we ordering? How do we monitor the disease? Because that’s one of the most important questions the patient asks, because for different types of solid tumor, we get imaging, and we know that the tumor is growing or not. Where, for us, we look at the markers I had described previously. And sometimes, we maybe see small changes in the markers that are very concerning and worrisome for the patient, but sometimes they are not. So, I think asking questions about the testing and how we treat them and monitor the disease is a very important part of being a good applique for itself.  

Accessing Personalized Myeloma Treatment | What Patients Should Know

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Accessing Personalized Myeloma Treatment | What Patients Should Know from Patient Empowerment Network on Vimeo.

Myeloma experts Dr. Francesca Cottini and Dr. Ashley Rosko provide an overview of the latest advances in essential testing for myeloma and explain how results could affect care and treatment decisions. Drs. Cottini and Rosko also review available myeloma therapies and their hopes for the future of patient care.

Dr. Francesca Cottini is Assistant Professor in the Division of Hematology at the Ohio State University Comprehensive Cancer Center. Learn more about Dr. Cottini.

Dr. Ashley Rosko is Medical Director of the Oncogeriatric Program at the Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Rosko.

Download Resource Guide

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How Does Essential Testing Affect Myeloma Care and Treatment?

Transcript:

Katherine:

Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today we’re going to discuss how to access personalized care for your myeloma and why it’s vital to insist on essential testing.  Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Let’s meet our guests for today. I’ll start with Dr. Ashley Rosko. Dr. Rosko, welcome. Would you please introduce yourself? 

Dr. Rosko:

Hi everyone. My name is Ashley Rosko. I’m an associate professor at the division of hematology at The Ohio State University. 

I’m also the medical director of the oncogeriatric program here at The James and one of the myeloma physicians here at Ohio State. 

Katherine:

Thank you. Also with us is Dr. Francesca Cottini. Dr. Cottini, would you please introduce yourself to the audience? 

Dr. Cottini:

Sure. My name is Francesca Cottini. I am an assistant professor in the divisions of hematology at The Ohio State University. I see patients with multiple myeloma, and I also run my own lab where I focus on multiple myeloma basic research. 

Katherine:

Thank you both for taking the time out of your busy schedules to join us today.  

It’s no secret that it’s important for patients to take an active role in their care and treatment decisions, and I’m sure many viewers here today are doing just that. So, Dr. Rosko, let’s start with this question: Why do you think it’s essential that patients advocate for themselves and insist on better care?  

Dr. Rosko:

Yeah, so I think when it comes to uncommon diseases like multiple myeloma –  

Although we’re talking a lot about it here today, myeloma is an uncommon cancer, and when it comes to rare cancers, it’s really important for you to get care at either a comprehensive cancer center or a place where there is expertise specifically in multiple myeloma. 

And the reason why that’s so important, it’s recommended through the NCCN guidelines and other standing guidelines is because myeloma is a very – it’s a shifting and changing landscape when it comes to both treatment regimens, diagnosis, and there’s a lot of moving parts and pieces.

Such as, there is an uncommon cancer that when diagnosed, we do recommend that patients and with their caregivers and with their families and support be able to seek expertise care for these uncommon cancers. We work often in collaboration with our community team, but we would not be able to care for myeloma if it were not for our community partners. 

And so, it’s really, really important for patients oftentimes, when there’s been such a diagnosis, they can come to a comprehensive cancer center for a consultation or to be able to get a second opinion oftentimes. And then continue to get care locally. It really provides this overall guidance on the management and diagnosis of uncommon plasma cell disorders, and we’re happy to do that. 

Katherine:

Thank you for that. It’s helpful as we begin our discussion. Part of accessing more personalized care starts with test results. Dr. Cottini, what testing should take place following a myeloma diagnosis?  

Dr. Cottini:

So, once somebody is diagnosed with multiple myeloma, there are different types of tests that we need to get. Some are blood tests, some are urine tests, some are bone marrow tests, and others are just different types of imaging. So, the reason for all these tests is because multiple myeloma can kind of go everywhere and can cause the damage to different types of organs. 

So, if we look at blood tests, usually you would see that you get the complete blood count, so we can count the number of red blood cells, white blood cells, and platelets. And then we’ll look at kidney function, through a chemistry profile, calcium levels, multiple myeloma can affect bone cells can affect kidneys. And then, you will see some more sophisticated tests that are really important for the diagnosis of multiple myeloma but also for monitoring and seeing if you’re actually responding to the treatment or you are progressing. 

These two tests that you can see are kind of difficult to say, but very important and needs to be remembered. So, one is called serum protein electrophoresis with immunofixation. And the other one is free light chain assays. 

And the practicum with these two tests is we can identify the specific marker of the multiple myeloma cells and it is either something monoclonal protein or M-protein or kappa light chain numbers. And as I said before, these numbers can be monitored. So, in response to the treatment, they should go down. And then, unfortunately, if we see progression, they might go up again. 

And then, urine tests can also give the same type of numbers. Usually, we have our patient keep the urine for 24 hours, for a day, and we can see if there’s monoclonal proteins or light chains there, too. Then there is a least favorite test of all of them that is the bone marrow testing. So, this is very important for us, because it’s where most of the myeloma cells stay. So, we need to have a look at the bone marrow.  

We need like a piece of the bone and some of the liquid tissue to look at specific characteristics of the myeloma. And then, I said before, the myeloma can go to bones, so we need to kind of get some imaging of the bones. These are usually a set of X-rays – it’s called skeletal survey – to see if there is any area that is abnormal or at risk of fractures.   

Then, we are also looking at PET scan, which is a more sophisticated test that is based on sugar consumption. We know that myeloma cells and all cancers enjoy sugar, so with the PET scan, we can see visually where the myeloma cells are in the body.

Katherine:

What is cytogenetics? 

Dr. Cottini:

So, this is a really interesting question. So, cytogenetics, or FISH tests, are tests that practical tests allow us to look at the chromosomes of the multiple myeloma. 

So, everybody has 46 chromosomes, right? Multiple myeloma cells can have more of them or less of them. So, they can have – some myeloma cells have 17 chromosomes instead of 46. So, cytogenetics in the karyotype counts how many chromosomes there are. And then, there is another type of test that is called FISH test, or fluorescence in situ hybridization – I get all the difficult names – that practically look at specific area of chromosome. It can tell us if some areas of chromosomes are lost. That’s what you can read as deletions, or practically missing pieces of chromosomes.  

Or there are extra pieces of chromosomes. These are the amplification gains. Or if there are different pieces of chromosomes that stick together. And these are the translocational chromosomes. And all of these data are important for deciding for knowing how aggressive or difficult to treat the myeloma. 

Katherine:

Dr. Rosko, in many other cancers, we’ve been hearing about targeted therapies and immunotherapies. In some cases, a specific mutation or chromosomal abnormality may indicate that a particular treatment may be effective. Are we there yet in multiple myeloma care? 

Dr. Rosko:

Yeah, so, myeloma care is always a little bit different. So, myeloma, being a blood cancer, is different than other solid tumors and how we treat it is also a bit different. So, unlike solid tumors, in which we look at the size of a cancer and then if it’s in different places in the body. In multiple myeloma, it being a blood cancer, just by definition it’s throughout the body. So, we have to be able to estimate or stage cancers differently or stage myeloma differently. And it is based upon the cytogenetics that Dr. Cottini just outlined to you.  

So, to get back to your question, Katherine, I didn’t forget about, how do we define treatment, how are some of these therapies being defined specifically and personalized for persons with multiple myeloma? And we do do that. And it is based a lot upon the DNA of those cancer cells and whether or not they’ve acquired what I would call a standard-risk changes or whether or not they’ve acquired a biology that makes them tend to act more aggressively. Now, again, these DNA differences – not all cancers follow the book, and not all therapies are unique to these. 

But what it does help us to do as clinicians to say, “Well, we have standard risk mutations within these cancer cells, and then we can define oftentimes how many drugs a patient gets when they’re newly diagnosed. Just like many other cancers, our treatments for multiple myeloma can be a combination of pills or shots. And then, if patients carry mutations that tend to act more aggressively, we tend to be very aggressive with their upfront therapy. For many patients, we’d receive three medications. Patients with more aggressive disease biology may receive four medications. 

And it’s very unique upon many characteristics. It’s not only based upon the cancer cells’ DNA but also the health of the patient. The health of the patient really defines also the ability to tolerate treatment. So, many patients are – myeloma has a lot of heterogeneity to it, where some patients with myeloma can’t believe that they could possibly have this cancer. 

You know, it’s really kind of picked up subtly, with blood abnormalities. And then some patients with myeloma come into the hospital very very sick, with having kidney damage or having infection. And it runs the gambit between being asymptomatic really and having patients coming in quite unwell. That also influences our treatment decisions. So, when we think about the question about whether we have different immunotherapies or targeted therapies based upon the genetic changes within the myeloma cancer cells, the answer is yes, we do shape therapy that’s tailored around the type of abnormalities within the cancer cells. 

But unlike some cancers, where if the cancer cells carry a specific marker, we give a specific drug, that’s not quite where we’re at with multiple myeloma, in terms that providing therapy is saying, “If you carry this mutation, this is what you should get.” 

So, it’s a very long answer to say to you that we do personalize therapy based upon changes within the DNA, but we also base it upon how fit the patient is and how their health was prior to developing cancer. 

Katherine:

Thank you for that. Dr. Cottini, what mutations or abnormalities are you looking for? 

Dr. Cottini:

So, as Dr. Rosko said, and as I quickly previously mentioned, so there are different types of DNA tests that we can do. One is this FISH test, and that’s a standard test. It’s usually done practically everywhere. And it practically tells us if there are specific deletions or changes. 

And we don’t really have yet a specific medication that we know works for specific abnormalities. But all this information is important to decide, as Dr. Rosko said, number of drugs, and maybe that can be helpful in the future when hopefully thanks to the research, we will be able to say, “Based on this abnormality, you would benefit more from this type of treatment.”  

There are other types of tests. One is called DNA testing, so we look at the mutation. So, really to point to small changes of a particular gene. This is done not routinely, but I think it can still give lots of good information. And there are lots of genes that are normally myeloma, that has potential drugs that have been studied, those with multiple myeloma and any other type of cancer. 

Katherine:

Yeah. Dr. Rosko, what do the results of these tests tell you about prognosis? 

Dr. Rosko:

Yeah, I think this is a really important question. And, in my experience, when we encounter a patient newly diagnosed with myeloma, it is like drinking from a firehose in terms of the amount of information that we are reviewing and the amount of information that we are discussing with the patient and with their family. And oftentimes, we talk about this piece of these cytogenetic abnormalities, and we talk about – but I really encourage your patients and anyone who is listening in today to really take a deeper dive. 

Because sometimes it’s helpful as, one, you’re navigating a new cancer diagnosis, but that’s challenging in and of itself. And then, two, talking about a cancer, multiple myeloma, that is – most people don’t know so much about multiple myeloma, unlike breast or colon or lung cancer, and so I really encourage patients and their caregivers. And a lot of times this happens, where we’ll go over all the cytogenetic abnormalities, we’ll talk about how it plays a role in their overall treatment trajectory, and their prognosis, but also good just to circle back and say. 

Settling into what this diagnosis is, oftentimes, people on first time treatment. And then even sometimes months or even years into their diagnosis, they stop and they come back and they say, “Can we talk about this FISH data? Can we talk about what changes that I had within the DNA? What does this mean?” And that’s not uncommon at all.  

So, I really feel like for many people that are on the call here today, I think it’s important to say it’s okay to go back to your physician and say, “I’m learning more about this, now that I’m more familiar with what this diagnosis is, can we talk about these FISH changes, or can we talk about the stage of my cancer?” Because I think it’s oftentimes an overwhelming period of time to have a new cancer diagnosis. And I also want to just give permission to everyone on the call that it’s okay to go back and ask questions, even if it’s been months or years.  

So, having high-risk mutation can upstage a cancer and in the absence of high-risk mutations can downstage a cancer. So, what that really means is saying, “These biologic changes that are happening in the cancer cells give a sense of what we anticipate that the trajectory is going to be when someone is diagnosed.” 

Now, it’s imperfect. I feel like cancer just generally is unpredictable and there are many things that we try as clinicians. And especially with the experience that we have, to say, “This is what we anticipate the course will be like you, in terms of response, in terms of the cancer being quiet.” As you all know, multiple myeloma is not a curable cancer right now. And for all patients, when they’re diagnosed, they’re often able to get disease control and be able for that cancer to be put in remission. And we do focus on remission. 

I think that’s also something that I talk to my patients about. Even though we can’t cure it, we can certainly control it, and that’s a big part of what we do. So, when we get good disease control, we’ll talk more about next therapies, but that is how Dr. Cottini – Dr. Cottini is a wonderful scientific investigator and knows all of the latest and greatest when it comes to different mutations that are identified within cancer cells. We partner very closely with her in terms of  scientific investigation and how the mutations that were newly identified, too, play a role in terms of response to treatment, and how we’re able to best treat them.  

Katherine:

Thank you for that. Dr. Cottini, do you have anything to add as far as what type of questions patients should ask their healthcare team about test results?  

Dr. Cottini:

I mean, I think Dr. Rosko already pointed out the most important things. So, multiple myeloma is a rare disease, and it’s not as intuitive to understand as breast cancer, lung cancer, prostate cancer. 

So, it’s really important as a patient to understand which tests are we ordering. Why are we ordering? How do we monitor the disease? Because that’s one of the most important questions the patient asks, because for different types of solid tumor, we get imaging, and we know that the tumor is growing or not. Where, for us, we look at the markers I had described previously. And sometimes, we maybe see small changes in the markers that are very concerning and worrisome for the patient, but sometimes they are not. So, I think asking questions about the testing and how we treat them and monitor the disease is a very important part of being a good applique for itself. 

Katherine:

Thank you. Dr. Rosko, I’d like to move on to treatment. We know that multiple myeloma patients have a number of options and that many available therapies are used in combination. 

So, I’d like you to walk us through the options that are available. 

Dr. Rosko:

So, I’m going to start by how the best way that I can frame out when we talk about newly diagnosed versus patients when they have relapse. So, there are therapies that are available for patients that are FDA-approved when they are newly diagnosed with the cancer, and there are therapies that are approved only when a cancer has acted up again or relapsed. 

So, I’ll kind of frame it from patients who are newly diagnosed. And then, I also will talk more about relapsed therapies and what we’re able to offer to patients. So, in first, when we talk about treatment options, we frame treatment based on a couple things. So, one is, we talk extensively about the disease biology. So, that plays an important role in how we decide which treatment the patient should get.  

And then, the second part about how – I would probably say there’s about four main parts. And so, disease biology is one, and another thing has to do with the patient characteristics. In terms of the patient’s overall health prior to developing cancer, and also how the cancer has impacted their health in terms of everyday activities. Whether or not a person has really slowed down quickly, whether they’ve been in the hospital, and how it’s impacting their organs. Because that plays a role in terms of what we’re able to give patients.  

If a patient has advanced kidney failure, which can sometimes happen, or if you have to focus more on protecting their bones and if there’s concern about fractures and things like that. And then independent of patient characteristics in terms of overall health, the last part I talk to patients about is their own preferences. It’s a hard thing to talk about, shared decision-making in a cancer that most people have never heard about, but there is certainly – when we talk about options and there are, it’s important to talk about shared decision-making in terms of what’s most important to them and where they – and most patients will say, “Well, I just want the best medicine.” 

And I say to them, “Well, you know, we have lots of options, and that’s the best thing about it, but we also want to be cognizant of the real world, of giving best options,” and for example, Many of my patients – so, I’m at The Ohio State University, I’m here. And a lot of patients travel. I have a lot of older patients that I care for, and they’re very independent with travel. And I want to make sure that whatever therapies we’re getting for them, that we can do this in such a way that maintains their lifestyle.  

So, the beginning part of a treatment, it is broadly described as – when we talk about someone who was diagnosed with this, it’s this thing called induction. So, induction is when we give anywhere from two to four medications to be able to control their cancer and put it into remission. And we know that the cancer is in remission because, like we started out the conversation with Dr. Cottini, myeloma makes proteins. Oftentimes, it makes proteins, those proteins are not nutrition proteins but are cancer proteins that we can track in the blood. 

So, we can check them every month and to make sure that the patients are having a really good response, and as such, we’re able to define that they’re responding to their treatment. Because they have a beginning stage in induction, which they’re given treatment, and then the goal is to put patients put in remission. 

Depending on the overall health of the patient, a standard of care for most patients diagnosed with multiple myeloma is to undergo an autologous stem cell transplant. An autologous stem cell transplant is not a transplant in which you’re getting cells from your brother or sister and they’re being donated to you. They are your own stem cells. We get them out of you when your bone marrow is free of disease, and then we would admit you to the hospital for a more intensive therapy and give them back.  

That is often the standard of care for patients newly diagnosed with multiple myeloma and it is recommended for most patients. Some patients get – I like to think of it as a stem cell transplant not at the time of their initial diagnosis, but later on at the time of relapse or some patients are not candidates for a transplant or elect not to have a transplant. And all of these options are very personalized to the patient. It’s very hard to say that this is exactly what we do. 

Because it’s a strategy where it requires a lot of shared decision-making to make sure that we’re getting good disease control, good quality of life, and deep, deep remissions for our patients. So, then, if a patient gets a transplant, there’s a period of recovery, and then patients go on a pill most often, a maintenance pill that they stay on for indefinitely. 

Myeloma is also a cancer which has perpetual therapy. Very different than many other cancers, where there’s a beginning and an end, myeloma for the most part is perpetual therapy, where you get some form of therapy at higher dosages versus lower dosages over a period of time.  

So, I’m going to talk broadly about the classes of drugs that we have and how we use them to be able to define therapy. 

So, the first class of drugs are called proteasome inhibitors. Just like many other cancers, we use different types of drugs to be able to target different aspects of a cancer cell’s growth cycle.  

So, very similar to how we do other drugs, these are very specific to the cancer cell, and they’re very targeted. So, unlike some of our other kind of classic chemotherapies, many of these medicines that I’m going to talk about are very targeted at the cancer cells without causing too many other problems. 

So, proteasome inhibitors include drugs like bortezomib (Velcade), which is given as a shot, carfilzomib (Kyprolis), which is given as an IV, or ixazomib (Ninlaro), which is given as a pill. They have different indications, but they’re the same class of drugs.  

The next class of drugs is called immunomodulatory drugs, or iMiDs. This includes things like lenalidomide (Revlimid), pomalidomide (Pomalyst). Those are the most common, and then we sometimes use the drug that the original iMiD drug, which is called thalidomide (Contergan). 

These are all pills that patients take, and so that’s oftentimes very nice for patients to be able to provide therapy at home, very well-tolerated. The next class of drugs are called monoclonal antibodies. On a cancerous cell, there is a marker. 

And so, we use monoclonal antibodies to be able to target the marker on the cancer cell. What that means is very specific. To that cancer cell, so, the most common target is the CD38, that’s a marker on one of the cancer cells. And we use a drug called daratumumab (Darzalex), that can be given as an IV or a subcutaneous agent, or another drug called isatuximab (Sarclisa). We also have other markers on the plasma cell. There’s a marker called SLAMF7, which we have other drugs called elotuzumab (Empliciti), which is often used for patients more in the relapse setting.  

Katherine:

Dr. Cottini, I’m wondering if you could briefly go over CAR T-cell therapy and bispecific antibodies. 

Dr. Cottini:

Yes, of course. So, these are all our new therapeutic approaches for patients. And these are types of treatments that are given to patients that already went through their induction, they went into remission, maybe they had a bone marrow transplant. And then, after a couple of years or months, unfortunately the disease came back, and they need the new and different treatment options. So, these two strategies, CAR T and bispecific antibodies, really rely on the T-cells, on the immune cells of the patient.  

And they all focus and target a specific marker on the plasma cells, but they work a little bit differently. So, the bispecific antibodies – and we have different antibodies.  

Some are approved by the FDA, some are just in clinical trials trials. They practically recognize something that is on the plasma cells, on the myeloma cells, that can be BCMA, GPRC5D, or other targets. So, at the same time that I am able to get close by the T cells, the immune cells, and in this way, practically there is both the antibodies and also the immune cells which is activating and getting rid of the cancer cells. 

So, these are infusions. Often, they’re done initially in the hospital and then in the outpatient setting. Sometimes it’s even every week, every other week or so.  

CAR T are different strategies, and it’s a very smart way of trying to get rid of the cancer cells. So, practically, these are T cells.  

So, these are immune cells from you, from the patient. And they are practically taken and then brought to a very specific and clean facilities where these T cells are modified in order to be able to recognize the cancer cells.  

And then these cancer cells are sent back to us and then practically they are given into the veins to patient, and then there is this kind of reaction of these T cells, which are very peppy and aggressive to be able to kill all the remaining cancer cells. So, these are all the new strategies. 

Obviously, we are kind of like in the early process, but these are very promising therapies I think we’ll be maybe moved up front even with diagnosis in the next 10, 20 years, we don’t know. 

Katherine:

I want to thank you both so much for your thoughtful responses. And as we close out the program, I’d like to get a final comment from each of you. What are you excited about in myeloma research, and why should patients be hopeful? Dr. Cottini?  

Dr. Cottini:

So, I think that especially if we look back especially at where myeloma was 20 or 30 years, I think we have made so many progresses, and there is really hope for our patients. I’m very passionate about research. That’s what I do. That’s why I read paper, I publish paper, and I think that it’s the heterogeneity of our disease is huge, and it’s difficult to tackle. But we as researchers, as physicians are the ones that can look at these changes, and find new therapies for our patients. So, I think that research is the way to go to be able to finally cure our patients. 

Katherine:

Dr. Rosko? 

Dr. Rosko:

Yeah, I mean I go Dr. Cottini’s sentiments. The multiplying therapies for myeloma really provides our ability to prescribe and make myeloma more of a chronic illness for our patients. I think it’s really important to allow patients to get really good targeted therapy personalized to them. Of course, we all are looking forward here to deep remissions. We want to be able to do that in such a way where we have good quality life for our patients. 

I think, importantly, as part of this program does here, we have to create access. So, most of myeloma is treated in the community, and most myeloma is diagnosed in older adults. And I really think how important it is, we talk about clinical trials, and being able to get our patients on to clinical trials, and to be able to get more knowledge about the disease process of pathogenesis, which I think is just really pivotal. 

So, I’m excited about personalizing therapy to the individual’s health and really being able to increase access to all of these novel therapies that we have. For patients, often at specialized cancer centers, but I’m really interested in how we can increase reach and access for all of these advances in myeloma research to every patient no matter where they’re at. 

Katherine:

Well, thank you both for joining us today. And thank you to all of our partners. To learn more about myeloma and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us.  

What Should You Know About Emerging Myeloma Treatment Options? Resource Guide

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What Should You Know About Emerging Myeloma Treatment Options? from Patient Empowerment Network on Vimeo.

With myeloma treatment and research advancing quickly, it’s important to stay up-to-date on the latest therapies. Myeloma expert Dr. Jeffrey Matous reviews new and emerging myeloma treatment approaches, how these therapies work, as well as the potential risks and benefits of each option. Dr. Matous also shares resources for learning about myeloma and how to access better care.

Dr. Jeffrey Matous is a myeloma specialist at the Colorado Blood Cancer Institute and the assistant chair in myeloma research for Sarah Cannon Research Institute. Learn more about Dr. Matous.

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Related Resources:

What Are the Phases of Myeloma Treatment

 What Is CAR T-Cell Therapy for Myeloma?

 Tools for Choosing Myeloma Therapy

Transcript:

Katherine:

Hello, and welcome. I’m Katherine Banwell, your host for today’s program. Today’s webinar is about advances in myeloma treatment and how emerging therapies may affect your care decisions.  

Before we get into discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining me is Dr. Jeffrey Matous. Dr. Matous, welcome. Would you please introduce yourself? 

Dr. Matous:

Thank you very much, Katherine. I’m Dr. Jeff Matous, and I am physician at the Colorado Blood Cancer Institute, and also, the Assistant Chair in Myeloma Research for Sarah Cannon Research Institute here in Colorado. 

Katherine:

Thank you so much for taking the time to join us today. 

Dr. Matous:

It’s a pleasure. 

Katherine:

Before we get into our discussion, would you share with the audience how the field of myeloma has changed over the course of your career? 

Dr. Matous:

It’s unbelievable. I mean, I started treating myeloma back in the days of VAD, vincristine (Oncovin), doxorubicin (Adriamycin), dexamethasone (Decadron) 96-hour pumps with 40 pounds of dexamethasone that we put into patients, and wow. We didn’t have much else. We didn’t know how long to treat people, and then, in the 2000s, we have the revolution of all the new therapies, and it just keeps going and going and going. It really is an exciting to be in this field. 

Katherine:

Yeah. Let’s begin by sharing some advice for navigating myeloma care on a basic level. First, what testing should take place following a myeloma diagnosis? 

Dr. Matous:

Well, I think even before that, Katherine, I always tell my patients that an educated patient, like the people that are on this webinar, are the best patients, and so, when I meet a patient for the first time, we spend a lot of time educating patients even before we delve into a lot of the testing. 

And I refer them to excellent resources out there. Examples of these are the International Myeloma Foundation, or the Multiple Myeloma Research Foundation.  

There are others, of course, and so I really encourage my patients. In fact, I usually show them how to navigate these sites. And then, we get into testing, and testing in myeloma is multifaceted, because myeloma can affect patients in so many different ways. For example, it involves radiology studies to look for bone disease, urine work to see if the kidneys are affected by myeloma, a lot of blood work, and then, we also do a lot of testing to make sure that we understand the whole health of the patient, because that comes into play so much when we’re making treatment decisions in myeloma. 

Katherine:

Yeah. What factors impact treatment decisions? 

Dr. Matous:

Well, there are so many. One of the key ones is fitness, and fitness is a term that myeloma doctors use and rely on tremendously. 

And fitness, more or less, falls into a couple different categories. It’s more complex than that, obviously, but generally speaking, it’s too old or too frail, or young and vigorous and I stress to my patients that vigorous or frail is not determined by chronological age. It’s determined by your physiologic age. That’s really critical, so determining what your patient’s overall fitness is, is really important in myeloma. And then, we have to assess the risk of myeloma. I think we’ll talk about this a little bit later, because not all myeloma is the same and we treat myelomas differently depending on risk, certainly. And then, patient preference is a huge part, because there are so many ways to treat myeloma these days that we explore options with the patients and sometimes patients have pretty strong opinions about, you know, one type of treatment or the other, for example. 

Katherine:

What advice do you have for patients and caregivers related to working with their healthcare team in choosing a therapy? 

Dr. Matous:

Yeah. I think the big thing is to do some research on your own, but really, ask questions when you see your physician. I mean, ask questions about, for example, what are my treatment options? Are there clinical trials that might be available to me? What’s on the cutting edge in myeloma? What are the standard therapies? What are the pros and cons? And a question I often counsel patients to ask when they’re seeking other opinions is if you had 100 people like me and you treated them this way, how many would do well and how many would not do so well, and prognosis, and so forth. And then, the other thing I think is really important sometimes is gauging how experienced your physician is in treating myeloma, because we actually have data that shows that patients who are treated in myeloma centers actually fair a little better than those who are not. 

Involving a myeloma expert in your care doesn’t necessarily mean you have to get your care at that center. It just means you may want a myeloma expert on your team. Pretty much every doctor I know welcomes a myeloma person on their team, because the field is so rapidly evolving. It’s really hard to keep up with for a lot of people. 

Katherine:

Yeah. That’s great advice, Dr. Matous. Thank you. Stem cell transplant is often considered for myeloma patients. Can you talk about who this treatment option might be appropriate for? 

Dr. Matous:

Absolutely, so we’ve known for decades that, what I call high-dose chemotherapy, also called stem cell transplant, is a very effective and very potent treatment of myeloma and we’ve shown that time and time again in clinical trials, including some recent ones that are published just in 2022.  

And so, high-dose chemotherapy and stem cell transplant is not for everyone. You have to be fit enough to undergo it, and this is not age determined. It’s fitness determined. And then, a lot of people live a long way from centers that perform high-dose chemotherapy and stem cell transplants. 

If patients have to travel hundreds of miles, then sometimes that comes into play. Hey, I just can’t do this. I can’t get the time off, and uproot, and bring a caregiver, and travel 300 miles to get this care, so sometimes that comes into play. Physician bias definitely comes into play. We know that some physicians are stronger proponents of high-dose chemotherapy and stem cell transplant, and I fall into that category, but we have other physicians that may not even bring it up as an option to their patients. We know, for example, that African Americans and other minorities are notoriously under-referred for high-dose chemotherapy and stem cell transplant. A lot of decisions go into that, and again, this is one of those situations where if you’re transplant-eligible, that means you’re young and vigorous, and on paper, a candidate. You want to go, at the very minimum, consult with physicians that do high-dose chemotherapy and stem cell transplant and hear about that option. 

Katherine:

Yeah. You mentioned high-risk myeloma earlier. How do you determine if a patient is high risk or low risk? 

Dr. Matous:

Absolutely, so this is not uniformly agreed upon among myeloma doctors, but in general, we assess risk based on a few different things. One is called staging, and we stage myeloma unlike any other cancer, so it’s not staged like breast cancer, or lung cancer, or prostate cancer. It’s staged according to something called R-ISS, RISS, and you get, basically, a one, two, or a three.  

Those are your stages, and in general, if your stage three, you have higher risk disease, but even more than that, we’re beginning to understand how myeloma cells misbehave at the genetic level, and we know that there are certain genetic findings inside the myeloma cell that can convey higher risk features. It’s important to stress to patients that these are not genetic findings that they were born with or can pass on through hereditary. 

These are findings that occurred during the life of the patient that occurred by chance and developed inside that cell that turned into myeloma, and those are the genetic changes that we’re talking about. And we know that certain of these genetic changes confer higher risk disease. And in general, Katherine, if I see 100 people with myeloma, about 85 of the 100 will fall into what I call a standard risk category and about 15 percent will fall into what we call the high-risk category. 

Katherine:

Okay. That’s really good to know. Thank you. There are several treatment classes for myeloma, such as immunomodulatory therapy and proteasome inhibitors, for example. And they’re often used together.  

So, what is a combination therapy and why is it used so frequently for myeloma?  

Dr. Matous:

Absolutely, so with learned over the years in myeloma that combining different types of drugs that work in different ways, we call those classes, so different classes of drugs, combining them together is the optimal treatment for myeloma. 

And back in the day, we used to use two drugs. Then, we learned that three drugs are better than two drugs, and now, we have data that four drugs are better than three drugs. And so, we bring in drugs from all kinds of different categories for our patients. And we even know that for the non-transplant-eligible patients, for the older patients, for example, that combining drugs from different classes is really, really important to get the best outcomes. And in general, the three classes that we use – the four classes that we use when we’re treating myeloma patients initially include the immunomodulatory drugs, and examples of those are lenalidomide, also called Revlimid. pomalidomide, also called Pomalyst.  

Thalidomide’s (Thalomid) an older drug, but we still occasionally use it.  

And then, we have the proteasome inhibitors. Examples of those are bortezomib (Velcade), carfilzomib (Kyprolis), and to a much lesser extent, there’s one called ixazomib (Ninlaro). And these days, we know that CD38 antibodies are really important and really getting their foothold into the initial treatment of myeloma.  

Examples of CD38 antibodies are daratumumab (Darzalex) or isatuximab. And then, usually, we combine these treatments with steroid medicines to sort of increase the effectiveness of the regiments. That’s how – those are the classes that we use when we’re treating myeloma. 

Katherine:

Okay and have you learned about adding one treatment to another to another through clinical trials or is trial and error? 

Dr. Matous:

Absolutely. We would not be where we are right now without the conduct of clinical trials. I always tell my patients by the time something’s approved in myeloma, and we had things approved in 2022, the field is already moving past that in clinical trials. It’s unbelievable. So, I’ll give you an example. When daratumumab, one of these antibodies, got approved by the FDA, already when it got approved by the FDA, we knew through clinical trials that were being conducted that combining it with other types of medicines was far more potent. 

And we have countless examples of this, so yeah. Absolutely, so every treatment that we use in myeloma, we discovered and developed through a clinical trial. And I always encourage my patients strongly to consider clinical trials, and then, we have to explain, because when patients hear clinical trials, and I could be deviating a little bit here, Katherine.  

They often think about experimentation and testing things that are unproven. In myeloma, we occasionally do that, but far and away, the overwhelming majority of our clinical trials are testing agents that we know are effective. We’re just trying to figure out what the best combination is and make sure that it’s safe for patients. 

Katherine:

Yeah. Dr. Matous, some of our viewers may have already been through some therapy at some level. Let’s dive into new and emerging treatment. CAR T-cell therapy has been approved for myeloma patients and it’s certainly a hot topic right now. Can you tell us about this treatment and who it might be right for? 

Dr. Matous:

Absolutely, so these T-cell therapies in myeloma are really exciting, and basically, how they work is T cells are cells that normally, in our body, they’re part of our immune system. When they see something foreign, usually, it’s a foreign infection or some kind. T cells go into kill mode and take out the foreign invader, and they’re supposed to do this with cells that are thinking about turning into cancer, but for various reasons, cancer cells can escape the T cells, and then, kind of brainwash the new system to say, hey. It’s okay if we coexist with you. No big deal. We’ll just hang out together. Okay? And that’s not okay. And so, in CAR T-cell therapy, what we do is we take the patient’s T cells.  

We remove them from the blood with a procedure called apheresis, which is a machine that many patients might be familiar with through their stem cell collections. 

It’s the same machine. And we collect these T cells. Then, they go to a laboratory where they are genetically modified in the laboratory using very sophisticated techniques to become myeloma killers. And we tell – we educate the T cells to become myeloma killers. We grow them up in sufficient numbers, and then, we return them to the patient. We just, basically, put them back in the patient’s bloodstream in the vein and they go and they are really effective at killing myeloma cells. And that’s CAR T-cell therapy, so it’s an amazing immune therapy. It’s way more complicated than I laid out, of course, but that’s the general thought behind it. 

Katherine:

What are the risks of this therapy? 

Dr. Matous:

Absolutely, so we have a lot of patients who come and ask about CAR T-cell therapy and think that it’s the same thing as getting daratumumab in the clinic or carfilzomib in the clinic.  

Get it and you’re on your way. Far from that, and so, CAR T-cell therapy has a lot of risks. The risks fall into a few different categories. The first risk is called CRS, which doesn’t stand for what you think it stands for. It stands for Cytokine Release Syndrome. This occurs when the T cells recognize the myeloma cell and kill it, and when they do this, a lot of substances get released in the body that can cause a lot of symptoms, like fever, or low blood pressure, or low oxygen, and this requires specialized management to shepherd people through this.  

This almost always occurs in about the first week of the treatment after the patients receive the CAR-T cells. In addition, patients who receive CAR-T cells can have what’s called neurologic toxicity that falls into many different categories. It can be something as simple as a headache, or a transient or temporary difficulty, you know, saying words or being confused, or in the most severe situation, even a seizure. 

This requires a lot of close monitoring for neuro toxicity. In addition, we know that patients that get CAR T-cell therapy are, for quite a while after they receive the CAR-T cells, an increased risk for infection. It’s very suppressing of the immune system, immunosuppressive. And lastly, a lot of our patients who go through CAR T-cell therapy have low blood counts for a long time and they have to be monitored for this, might need transfusions, or some different therapies. It’s a complicated therapy for sure. 

Katherine:

Yeah, so what questions should patients be asking their doctor when considering CAR T-cell therapy? 

Dr. Matous:

I think the first thing, of course, is am I a candidate, because the commercially approved CAR-T cells, there are very specific criteria for who’s a candidate, who could receive it. Okay, and then, you want to know, one, if you’re a candidate. Two, what the risks and benefits are. 

Three, are there alternatives besides CAR T-cell therapy. Is it too early or too late to do this? Should we think about maybe another clinical trial or one of the T-cell redirecting antibodies, for example? You want to ask those questions for sure. These treatments are tremendously expensive, of course, and so that may come into play, as well. You want to know what the experience of the center is with CAR T-cell therapy, I think, and then, you also want to know are there clinical research studies for which you might be eligible to have CAR-T cells, not just commercially available ones, because we have two that are commercially available right now, and we have scores of CAR T-cell treatments that are still in clinical trial. [22:32] 

Katherine:

Yeah. Well, thank you for that, Dr. Matous. 

I know many viewers will appreciate all of this information. Let’s switch gears now to another therapy we’ve been hearing about; bispecific antibodies. One has been recently approved for myeloma, teclistamab, so let’s start with what are bispecific antibodies and who might they be right for? 

Dr. Matous:

And strap on your seatbelt, because there’s a whole bunch of them coming, I think, for approval. So, the T-cell redirecting antibodies, it’s a different strategy for trying to get your T cells, the patient’s T cells, to attack the myeloma cells. And in CAR T-cell therapy, it’s a single infusion. That’s the treatment. And the bispecific antibodies that I often call T-cell redirecting antibodies, because they redirect the T cells to the myeloma cell, these are given over a continuous period and it might as long as you tolerate it, as long as it’s working. It might be for a year. And they are given either under the skin as a subcutaneous injection, or in the vein. 

And there are many, many different of these T-cell redirecting antibodies, the bispecific antibodies. How they work, I just do this with my patients. I hold up my hand and I say the bispecific antibodies have two hooks on them, and one hook recognizes the T cell and latches onto the T cell, and the other hook latches onto the myeloma cell. And then, what it does, it brings the T cell in proximity to the myeloma cell. Then, the T cell says “Oh, aha. I’m supposed to kill this myeloma cell,” and usually does it. Now, the part that connects the T cell and these bispecific antibodies is always the same. It’s CD3. However, the part that sticks on the myeloma cell, there are different targets, and you referred to teclistamab (Tecvayli), which was approved by the FDA, and that attaches to something on the outside of a myeloma cell called BCMA, BCMA. 

But we know that other bispecific antibodies that can attach to different markers or antigens on the outside of the myeloma cell and affect the same change, and so, I think these are going to be coming fast and furious. 

Katherine:

Who’s this class of treatment right for? 

Dr. Matous:

I think – well, again, the FDA approval right now is for people who have seen pretty much everything. You know, you’ve had a lot of treatments. You’ve seen all the different classes of the myeloma drugs, but in our clinical research trials right now, we’re testing these as an initial therapy, in second-line therapy, after stem cell transplants. They’re being tested pretty much in every scenario right now in clinical trials, so right now, it’s when you’ve exhausted the normal treatments and you’re considering CAR T-cell therapy, or you’re considering getting treated with a drug called selinexor (Xpovio), or looking at another clinical trial. That’s when it’s the time to ask about the bispecific antibodies. 

Katherine:

What are the risks and benefits of this therapy?  

Dr. Matous:

The risks are pretty similar to the risks from CAR T-cell therapy, so Cytokine Release Syndrome. That usually occurs during the first week. Neurologic toxicity is, I think, less frequent with the bispecific antibodies, but infections and low blood counts definitely a concern with these bispecific antibodies, requires a lot of monitoring without any doubt.  

Now, the other thing about the bispecific antibodies, there’s, right now, they’ve been in the realm of the larger centers, so myeloma centers is where people have been getting these bispecific antibodies, but there’s absolutely no question in my mind that these bispecific antibodies are going to be available through almost every general hematology, oncology practitioner’s office, but not for a while. The docs that aren’t used to giving these medicines are a little – they’re being quite cautious rolling them out in their practices right now. There are still a lot of questions as these roll out, and so, right now, I think teclistamab is still largely unavailable outside myeloma centers, but that’s going to change, I think, even over 2023 and definitely into 2024. 

Katherine:

Okay. That’s really good news. For patients who want to know more about bispecifics, what questions should they be asking their healthcare team? 

Dr. Matous:

Again, the same thing is – the same questions. Well, teclistamab is approved by the FDA. What other bispecifics are there? What about combinations? What about clinical trials? And then, that’s what you want to ask for sure. Then, how often do I need to come in the office? With teclistamab, the answer is weekly.  

If they say for how long, it’s until it quits working or you have side effects, and then you can’t take it anymore. That’s the way the FDA label is. And so, it’s a big commitment to go on these treatments, but they’re effective. You ask me about the effectiveness of these drugs and, essentially, all the studies with these different bispecifics, including teclistamab, have been studied initially in people who have seen every myeloma treatment. They’ve had an average of about six different myeloma treatments. 

They’ve seen all the drugs. They’re not working anymore. They’re in trouble. They’re in a pinch, and roughly, seven out of ten people have dramatic responses to these bispecifics when they’re treated, which we’ve never had anything like this at all in the myeloma world. 

Katherine:

Wow. Do the side effects go away at some point? 

Dr. Matous:

The side effects are completely manageable. Yeah and you can – by and large, you can adjust the bispecific, either the schedule or different things, to make these completely tolerable for patients. 

Katherine:

Okay. 

Dr. Matous:

Very few patients on our trials, with these bispecifics, who we have not been able to manage and, pretty much, handle all the – any side effect that occurs. 

Katherine:

Okay. That’s good. Are there other emerging myeloma therapies that patients should know about? 

Dr. Matous:

There are a bunch of other therapies. Looking at in myeloma, for sure, and a lot of these other therapies are – they’re exploring the same pathway where the proteasome inhibitors work, but in a little different way. 

And proteasome inhibitors, again, just to refresh your memory, are  Velcade or bortezomib, Kyprolis or carfilzomib, and there are different drugs that work in this area that are being explored. And also, for the immunomodulatory drugs, there are different what are called cell mod or cell-modifying drugs that are being developed. Also, at our recent hematology meeting last December where all the blood doctors get together, there was a lot of research presented looking at using different cells for attacking the myeloma, for bringing back an old friend, interferon, to fight the myeloma through a new sophisticated way. The field is just really going at breakneck speed right now. 

Katherine:

Where do clinical trials fit into myeloma care? 

Dr. Matous:

I’m biased, Katherine. I think in every step of your myeloma journey you should ask about a clinical trial, because clinical trials might be appropriate as initial therapy, second-line therapy, third-line therapy, post-transplant maintenance therapy. There are clinical trials available, pretty much, at every phase of myeloma care, and so, I think it’s important that you here about your clinical trial options when you’re talking with your physician. Now, for some folks, it’s going to be hard to get on a clinical trial. You might be a long way from a center that does very many clinical trials, but you should always, always ask about it and there are many resources for researching clinical trials that are out there, right? One example is you can call The Leukemia & Lymphoma Society and they have counselors on the phone that can guide you toward clinical trials. You can go to clinicaltrials.gov. You’re paying for it. Might as well use it and search clinical trials there. It’s a pretty easy site to use, as well. 

My answer is at every phase of your journey, whenever you’re considering a treatment or a new treatment for myeloma, you want to know what your clinical trial options are. 

Katherine:

How can patients and care partners stay informed about the latest myeloma research? You mentioned a couple of websites. Are there others? 

Dr. Matous:

There are. There are a bunch of these that are out there, right? There’s the Myeloma Crowd. There’s – you know, this webinar. The Leukemia & Lymphoma Society in the Rocky Mountain area, we have, every year, a blood cancer conference that we put on free for patients through The Leukemia & Lymphoma Society that reviews new goings on in the field of myeloma, so there’s a lot of information out there and just a little bit of effort on the web. You can find great resources. Again, the ones I mentioned earlier I think are my top ones. Particularly, the IMF, the International Myeloma Foundation, because the physicians who run that and the people who run that, they made sure that everything that’s on there is entirely believable. 

Katherine:

Yeah. Okay. Let’s get to a few audience questions that we received before the webinar. Kendall writes, “I’m in the maintenance stage following initial diagnosis and treatment. At first relapse, is it appropriate to push for stronger treatment in hopes of a cure?” 

Dr. Matous:

Yeah, so the answer to that has changed. The answer is yes, and so, the – it used to be said in myeloma that your best treatment was your first treatment. Then, if you relapsed, that the treatments didn’t work as well, and the remissions did not last as long. Throw it out, so now, we get multiple chances to get really deep remissions in patients, and we should be every bit as greedy when we’re treating relapsed disease, at least initially, as we are when we treat disease at the very beginning. We know, for example, that there are many second-line therapies. I’ll just throw out some examples – daratumumab, pomalidomide dex, daratumumab Revlimid dex, daratumumab Velcade dex.  

Not to mention, the T-cell therapies that can put patients in remissions that are so deep that we can’t even find myeloma cells using very sophisticated molecular techniques, so be greedy. 

Katherine:

Yeah. Okay. Good advice. PEN community member, Greg, sent in this question. “Can you discuss any future or potential changes to using stem cell transplant for myeloma patients?” How would you counsel patients who do not want to pursue a transplant as a treatment option? 

Dr. Matous:

So, for stem cell transplant in myeloma, for years, it’s been the standard of care for suitable patients. And every couple years, I liken this to that game we used to play called King of the Hill growing up where stem cell transplants, King of the Hill, and everyone tries to knock stem cell transplant off the hill. And so far, it really hasn’t happened. And so, transplants still, I think, an important part of the overall care for suitable patients. 

For patients who are eligible and safe enough to undergo transplant. However, not all – now, will this be challenged in the future? And the answer is – I think the next challenger, and this will be a serious challenger, will be CAR T-cell therapy. And so, we have to figure out if CAR T-cell therapy or the bispecific antibodies are safe enough to give at the beginning and as effective as stem cell transplant and what the long-term side effects, how they might differ, as well, so that question is going to be tackled in the myeloma word, but it’s going to be several years until we have an answer there, for sure.  

So, for my patients who are otherwise candidates for stem cell transplant, but who don’t want to do it, usually, I’ll say, “You may change your mind in the future. In myeloma, it’s important to keep all your options open and you should at least discuss with the transplant center collecting and freezing away your stem cells for a rainy day to keep that option open to you.” So, even you’re thinking of not doing it, it might be a good idea, it probably is a good idea, to harvest and store your stem cells at a transplant center. 

And then, if you’re not going to do transplant up front, they key is to stay on prolonged maintenance therapy.  

We know that that’s one of the keys for making survival as long as possible in patients who don’t do a transplant is to continue on ongoing maintenance therapy as long as possible. Don’t curtail your therapy just because you’re not doing a transplant. 

Katherine:

Right. Okay. Well, thanks for that, Dr. Matous.  

Those were all great questions. Please continue to send them in to questtion@powerfulpatients.org and we’ll work to get them answered on future programs.  

So, Dr. Matous, as we close out the program, we’ve definitely learned that the field of myeloma is advancing very quickly. Would you share with us why you’re hopeful? 

Dr. Matous:

Yeah. It’s because for – I’ve been doing this quite a while and I always used to tell my patients if you just hang around. 

If you stay in the game, something else is going to come that we don’t even know what it is right now that’s going to impact your life, your quality of your life, the longevity of your life, and be a good treatment for you. And so far, that’s been the case. And right now, with the T-cell therapies, I’m really, really excited about how they can impact the cure of our patients. I also think that the basic research that’s going on in myeloma right now, and this is done by the real smart scientists, not the clinicians like me, but the really smart people that work in the laboratory. Learning how myeloma cells misbehave at very amazing levels, and when we learn that, it almost always results in a treatment that benefits our patients.  

And so, I think that we have every reason to be optimistic for our patients with myeloma, because of all the treatments that are coming out that we know about, that we know are around the corner, and for those that we don’t even have an idea what they are yet. 

Katherine:

Yeah. Well, it seems like there’s a lot to be hopeful about in myeloma care. Dr. Matous, thank you so much for joining us today. It’s been a pleasure. 

Dr. Matous:

Well, the pleasure’s been mine. I love talking to myeloma patients and I would just encourage you to keep getting all the information you can. The field’s moving really fast. Just keep up with it and don’t lose hope. 

Katherine:

Yeah. And thank you to all of our partners. To learn more about myeloma and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us.  

Is There Financial Assistance for Myeloma Patients?

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Is There Financial Assistance for Myeloma Patients? from Patient Empowerment Network on Vimeo.

Can myeloma patients access financial assistance for their care? Expert Dr. Benjamin Derman shares information about available support and resources to reduce the financial burden on patients.

Dr. Benjamin Derman is a hematologist and oncologist specializing in multiple myeloma at the University of Chicago Medicine Comprehensive Cancer Center. Learn more about Dr. Derman.

See More from Engaging in Myeloma Treatment Decisions

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The Role of a Myeloma Specialist on Your Care Team

 How Can You Engage in Your Myeloma Treatment Decisions? Resource Guide

 Expert Advice for Newly Diagnosed Myeloma Patients

Transcript:

Katherine:

One final question for you. Jennifer asks, “Many new medications for treatment were mentioned. And I’m sure these could be expensive. What are the options to make these available financially for patients who need them?”  

Dr. Derman:

That’s a really good question, and one that we don’t yet have great answers to. As a physician, I don’t receive compensation based on the drugs that I prescribe. And so, I do know – I often have a good sense of what these drugs cost. A lot of the costs that are passed along to patients typically revolve around oral therapies. Even patients who are on Medicare, or sometimes especially patients who are on Medicare. And looking at some of the policy changes that seem to be coming down the pike that include capping Medicare out of pocket costs for medications will be a huge benefit to our myeloma patients.  

It’s important to familiarize yourself with different organizations and the financial support that may be available. Just to name a few, and you’re not limited to these, but The Leukemia & Lymphoma Society does a really great job in providing financial support to patients. But there are definitely other programs that can be contacted for this.  

And also, a lot of the pharmaceutical companies will actually have patient assistance programs as well. Sometimes it’s as simple as asking your provider, and typically they will have their team look into this for you. But we’re fortunate to have a team of pharmacists and my nurses as well who are used to doing this kind of thing. So, it’s important to look into those as well.

How Can Myeloma Patients Cope With Fatigue?

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How Can Myeloma Patients Cope With Fatigue? from Patient Empowerment Network on Vimeo.

Fatigue can have a big impact on daily life for people with myeloma, so how can this common symptom be managed? Expert Dr. Benjamin Derman shares insights about why fatigue occurs, advice about treatment timing, and recommended adjustments to optimize energy levels.

Dr. Benjamin Derman is a hematologist and oncologist specializing in multiple myeloma at the University of Chicago Medicine Comprehensive Cancer Center. Learn more about Dr. Derman.

See More from Engaging in Myeloma Treatment Decisions

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What Factors Affect Myeloma Treatment Decisions

 How Is a Myeloma Patient in Active Treatment Monitored?

 Expert Advice for Newly Diagnosed Myeloma Patients

Transcript:

Katherine:

Craig sent in this question prior to the program. “My primary side effect is fatigue.” And you just mentioned that. “What advice do you have for planning activities through the day?”  

Dr. Derman:

So, this is a very common side effect that we see. In part, it can be from the disease itself. And if that’s the case, it’s going to get better as treatment works. In other cases, it’s due to the treatment itself. And sometimes there are controllable aspects. If it’s a pill, let’s say, where you can control the timing of when you take it. I often tell patients, “Take the drug at night. Because if it makes you tired, at least you’re going to be going to sleep at that point.” 

I do think making sure that you have a good night’s sleep is important. I think making sure that you keep your day-night cycles. So, even if you feel fatigued and you’re at home, it’s not good to be having the windows closed and not being exposed to the outdoors at all. You need light during the day. That’s a normal human need. We do the same thing when patients are in the hospital, and it’s very easy to get your day and night cycles messed up.  

And the other thing too is planning periods of the day when you know that your activity level is going to be, or your energy level is going to be higher, and planning your activities around those times. I think those are at least some important things that we can do.  

Myeloma Maintenance Therapy | What Patients Need to Know

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Myeloma Maintenance Therapy | What Patients Need to Know from Patient Empowerment Network on Vimeo.

What should myeloma patients know about maintenance therapy? Expert Dr. Benjamin Derman discusses the role of maintenance therapy, data presented at the 2022 American Society of Hematology (ASH) meeting, and the role of minimal residual disease (MRD) testing in myeloma care.

Dr. Benjamin Derman is a hematologist and oncologist specializing in multiple myeloma at the University of Chicago Medicine Comprehensive Cancer Center. Learn more about Dr. Derman.

See More from Engaging in Myeloma Treatment Decisions

Related Resources:

How Can Myeloma Patients Cope With Fatigue

 What Are the Phases of Myeloma Treatment

What Are the Phases of Myeloma Treatment?

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Transcript:

Katherine:

When a patient goes into remission, they’re often placed on a maintenance therapy. What’s the role of maintenance therapy in myeloma care?  

Dr. Derman:

Yeah. So, maintenance, just to specify, is typically something that we call a long duration of usually, less intensive therapy after a more intensive schedule of therapy. So, the most common area that we talk about maintenance is after, let’s say, an autologous stem cell transplant, which came after induction therapy that I mentioned.  

But for patients even who don’t go to a stem cell transplant, they can also go on maintenance therapy. So, when we think about the frontline setting, which in this case would be induction transplant maintenance, the most commonly used drug is a single agent lenalidomide (Revlimid). And that’s been shown to have survival benefits not just in keeping the disease away, but also helping patients live longer. So, maintenance therapy does seem to carry some real importance. One of the things though that we don’t know, is really how long patients need to be on maintenance therapy.  

So, we can all accept I think in the myeloma field, if there’s one thing we can agree on, is that maintenance is important. But the question is, what makes up that maintenance therapy? And then how long? Those are questions we don’t really have the best answers to. And actually, one of the areas that I do quite a bit of research in is about this, how long do patients need to be on therapy?  

So, we recently published some – we presented at ASH this year in 2022, some recent data, at least a preliminary data on patients who had really deep responses, and who we stopped their maintenance therapy after at least one year – but the average was about three-and-a-half years on maintenance therapy – to see if the disease would actually be at risk of coming back.  

And so, what we’re finding is that even in the first year, about 85 percent of patients did not have their disease come back after stopping therapy. So, maintenance therapy is certainly important, but I think we still have to figure out how long patients need to be on that therapy.  

Katherine:

Right. And I can imagine that each person, each patient is different, and some – the maintenance therapy would work really well for them for a long period of time. For others, not necessarily.  

Dr. Derman:

Yeah. I mean, a lot of it comes down to the risk there of the patient’s myeloma. And what I mean by that is – so, somebody has explained to me previously, and I really like the analogy that myelomas are kind of like people. They have different personalities, and they give first impressions. And sometimes your first impression of a myeloma may end up being wrong. You thought it was going to be really hard to treat and you found out that it actually responded pretty nicely to therapy. And other times, it’s the other way around.  

But for the ones that give us a bad first impression, we’re going to be treating those patients typically more aggressively. At least that’s my personal approach. And I take that all the way through from induction, to transplant, even into maintenance therapy where I mentioned already, most people will prescribe a single drug as maintenance therapy. But for those patients, I’m typically going to be prescribing more than that. Or I will continue more aggressive therapy for longer. So, that’s where you have to sort of adapt your therapy in some cases to the patient and their disease characteristics.  

Katherine:

Related to maintenance therapy, we received this question before the program. How do doctors feel about maintenance breaks if you are MRD-negative? Or in a very good response?  

Dr. Derman:

So, I want to be very careful about how I respond to this. Because what I’m going to say is, there’s currently no data to tell us that patients should stop. I mean, in part that’s, you should stop therapy. In part that’s what I’m hoping that we can answer with our study. There’s another large cooperative group study trying to answer this as well, about the duration piece and whether people can stop.  

So, a very good partial response signifies at least a 90 percent reduction in the tumor, in the myeloma, but not 100 percent.  

And there’s also a complete response, which means there’s no detectable disease by conventional methods in the bone marrow or in the blood, but that there can still be microscopic or low levels of cancer cells which we call minimal residual or measurable residual disease. Also called MRD.  

So, MRD negativity is a not so nascent field now, where we are trying to quantify small amounts of cancer cells that may still be present. And the theory is that the presence of residual disease at a small measurable level is what’s ultimately responsible for myeloma relapsing.  

We used to think like, “Oh, a patient is in a complete response. That’s amazing. Let’s clink our champagne glasses. Let’s celebrate.” And there’s still cause for celebration for that. That is a great achievement. But we know that that doesn’t mean we can rest on our laurels. If there is MRD-positive disease, then the disease, it can likely come back. And that’s where suppression of the disease with something like maintenance therapy with lenalidomide is probably helping a lot.  

Katherine:

Yeah. 

Dr. Derman:

But let’s say we have people who don’t have detectable disease, the question is, can they stop? And like I mentioned, we’re trying to answer that question. I would say right now, there’s no recommendation for that. I can’t say in good faith that you should be doing that, unless it’s as part of a clinical trial, which is what we’re hoping to answer.  

What Is Known About the Risk of Myeloma Relapse?

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What Is Known About the Risk of Myeloma Relapse? from Patient Empowerment Network on Vimeo.

Myeloma relapse is common, but what is known about the the probability of relapse? Expert Dr. Benjamin Dermain explains the significance of clinical trial data and the important role of blood work, including monitoring M-spike and light chain levels.

Dr. Benjamin Derman is a hematologist and oncologist specializing in multiple myeloma at the University of Chicago Medicine Comprehensive Cancer Center. Learn more about Dr. Derman.

See More from Engaging in Myeloma Treatment Decisions

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What Are the Treatment Options for Relapsed/Refractory Myeloma

 Relapsed and Refractory Myeloma Defined

Relapsed and Refractory Myeloma Defined

 Expert Perspective Advances in Treating Relapsed and Refractory Myeloma

Transcript:

Katherine:  

Is research being done to determine the likelihood of relapse and when that might occur?   

Dr. Derman:  

Yeah. I mean, we can look at clinical trial data for regimens that have been tested in the relapsed or refractory setting and say, “Okay, we know that this three drug regimen typically gives patients a year before the disease comes back.” Or “This one gives two-and-a-half years or three years.” So, that’s one piece.  

But when you think about who – if you wanted to know ahead of time, “Okay, a patient with high-risk disease, they’re likely not to have as good of a response.” But nobody knows ahead of time the exact amount that they’re going to relapse.  

But one of the things that we focus on, part of the reason that patients get a good amount of blood work when they have myeloma and they’re on therapy is that we have a measure in the blood, or we have several measures in the blood, where we can monitor for relapse. So, we can look at the abnormal proteins, what we call paraproteins in the blood. Either as the M-spike, is what it’s called, or light chains. We look at both of those to see if there are increases in those numbers over time.

When a patient’s responding, those numbers come down. When a patient is losing response and their disease is progressing, that’s when we start to see those numbers go up. And that’s often an indication that we need to switch treatment, even before a patient develops symptoms related to their myeloma.   

What Are the Treatment Options for Relapsed/Refractory Myeloma?

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What Are the Treatment Options for Relapsed/Refractory Myeloma? from Patient Empowerment Network on Vimeo.

What do relapsed/refractory myeloma patients need to consider when choosing a treatment approach? Expert Dr. Benjamin Derman explains the impact of previous therapies on options, various treatment classes available, and why combination treatments may be optimal.

Dr. Benjamin Derman is a hematologist and oncologist specializing in multiple myeloma at the University of Chicago Medicine Comprehensive Cancer Center. Learn more about Dr. Derman.

See More from Engaging in Myeloma Treatment Decisions

Related Resources:

What Are Current Myeloma Treatment Approaches

 Myeloma Induction and Consolidation Therapy Defined

Myeloma Induction and Consolidation Therapy Defined

 Making Myeloma Treatment Decisions at Every Stage of Care

Transcript:

Katherine:

Unfortunately, relapse is common among myeloma patients. Or it may be that a treatment stops working, and so the person’s myeloma becomes refractory.   

When considering a treatment for relapsed or refractory myeloma, are there different questions that patients should be asking their healthcare team?  

Dr. Derman:

Yeah. I mean, that’s a great question. I think part of it is every patient’s journey with myeloma ends up being quite unique, in part because we don’t have a lot of consensus in terms of how to treat myeloma. So, I may choose one regimen, but the other doc down the street is going to recommend a slightly different one. And now, they all have efficacy. No one’s going to be recommending something that’s not good, right? But what it means is that the journey, the number of therapies, the types of therapies that a patient has received are all going to be quite different than the next.  

So in part, sometimes the past therapies are going to dictate what options are available.  

So, I mentioned some different classes of therapies. The proteasome inhibitors, there’s a certain number of those. The immunomodulatory iMiDs, there’s a certain number of those. The CD38 monoclonal antibodies, there are those. And then there are a few other drug classes as well. 

And if we’re using three or sometimes four drugs at a time for each what we call line of therapy, meaning each time a patient changes treatment – right? Eventually, we’re going to have gone through a number of treatments that now the patient would be – their disease would be resistant to. And so, you don’t really – it’s not really going to be prudent or wise to go back to therapies that didn’t work previously.

And so, we start mixing and matching, and we come up with regimens that we think are going to hopefully throw a curveball to the myeloma to really try to get rid of it again. That’s what I mean by it’s dictated by past therapy.  

Key Questions to Ask Your Myeloma Doctor About Induction Therapy

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Key Questions to Ask Your Myeloma Doctor About Induction Therapy from Patient Empowerment Network on Vimeo.

What key questions should you ask your myeloma care provider when choosing induction therapy? Expert Dr. Benjamin Derman discusses factors that are important for patients to consider when making treatment decisions along with their care team.

Dr. Benjamin Derman is a hematologist and oncologist specializing in multiple myeloma at the University of Chicago Medicine Comprehensive Cancer Center. Learn more about Dr. Derman.

See More from Engaging in Myeloma Treatment Decisions

Related Resources:

What Are Current Myeloma Treatment Approaches

 Myeloma Induction and Consolidation Therapy Defined

Myeloma Induction and Consolidation Therapy Defined

 Making Myeloma Treatment Decisions at Every Stage of Care

Transcript:

Katherine:

Let’s share some tips for having that conversation. I’d like to start with induction therapy, which is the first line of treatment for patients. What questions should patients ask when choosing therapy early in their diagnosis?

Dr. Derman:

Yeah, that’s a great question. And it’s of course – it’s really the patient priorities I would say. So, one of the things that I like to discuss with patients is, number one, what are the things that they value? And that’s a hard question to ask without any qualifiers.

So, one of the things that I often ask patients to think about is the – first of all, the number of visits to the medical center. Certain therapies are weekly, certain therapies may actually decrease in frequency overtime. So, if that is something, it’s hard to travel, it’s hard to get someone to take you or to come yourself, or you just don’t want to be in the clinic as much – right? If that’s your number one priority, there are going to be certain therapies that are – or regimens that may be better suited for that patient. If somebody says, “I don’t care how many times I have to come, my goal is the deepest response possible,” you can think about things from that standpoint.

I mentioned side effects. What are the things that are scary to you personally, as a patient? Some people may look at that neuropathy, as I mentioned, and say “No way. That sounds horrible. I can’t do my job.” Other people would say, “I already have some cardiac issues. I don’t want to take that risk.” Right? So, there are different side effects that we have to take into account.

Especially when it comes to talking about transplant, there is not just the acute issues that we have to deal with in terms of side effects, but also long-term immunosuppression. Meaning the immune system is suppressed, and there’s a risk of infections, and it’s going to be higher than if you had not gotten a transplant. So, those are at least some of the things that I encourage patients to be thinking about.

I would also say, on top of that, patients may be approached about clinical trials. And I work at a university where we really value enrolling patients in clinical trials. But that they do come with some inconveniences as well, even though I think they really help to advance the field forward, and sometimes offer patients options they wouldn’t normally be able to get. But there are typically more visits associated with that, more evaluations, more blood draws, more bone marrow biopsies, so those are things that you really have to take into account.