Dr. Joseph Mikhael:
Can a patient with type 2 diabetes receive dexamethasone during their induction? Hello everybody. My name is Dr. Joseph Mikhael. I'm the Chief Medical Officer of the International Myeloma Foundation. I have the privilege of hosting a Facebook Live program where I answer questions in real time from patients and their families and anyone else who wants to learn more about multiple myeloma.
There are so many questions that we can't answer them all live, so we've taken some time today to get to these questions. You can ask these questions on any of our social media channels, on Facebook, on Instagram, on X. Just use the hashtag #AskTheIMF and we'll be happy to answer your questions. So let's dive into these questions.
David asks, "The GRIFFIN and CASSIOPEIA trials seem to suggest that adding Daratumumab to triplet induction therapy seems to have greater impact than just triplet therapy alone. Are the results conclusive?"
Well, the short answer is yes. I think we really are seeing a transition in multiple myeloma. Just like we saw a transition when we used to use one drug, then we combined two drugs together, then we combined three drugs together, that now we're really moving towards four drug combinations. It's proving the principle that when we use different mechanisms of action together to fight myeloma, it's more effective than fewer mechanisms of action.
The two trials that David referenced, the GRIFFIN and the CASSIOPEIA study, were studies where we added Daratumumab to the standard three drug or triplet induction regimen of Velcade, Revlimid and Dexamethasone. But interestingly, we're now seeing this in many other studies as well. Not only for patients who are eligible for transplant, but patients who are typically ineligible for transplant as their first-line therapy receiving a CD-38 monoclonal antibody like Daratumumab, also called Darzalex, or Isatuximab, also called SARCLISA, being added to the typical triplets, be it VRD, Velcade, Revlimid, Dexamethasone, or KRD, Kyprolis, also known as Carfilzomib, Revlimid, and Dexamethasone.
Great question, David. Let's move to another question. Here's one that comes from my friend Steve Weinstein, and he says, "Can a patient with Type II diabetes, fasting blood sugar in the 150s, receive Dexamethasone as part of induction maybe at a lower dose?" Well, Steve, you partly answered your own question. The short answer of course is yes, we can use Dexamethasone, but we have to use it a little bit more carefully. So Dexamethasone is this interesting drug that we've had in myeloma for many years, which really boosts the effect of every drug that we use in myeloma. In my clinic, I sometimes say it's like the booster rockets on the shuttle. Really helps things go up, but with time we have to dose reduce it. The challenge with Dexamethasone, of course, it causes lots of side effects, and in particular it can bump up people's blood sugar, especially if they have type two diabetes.
So two things we typically do, one, we carefully monitor the dose that we're giving. Sometimes we start at 40 milligrams, but we may elect to start lower at 20 or 12 milligrams in a patient with diabetes. And then secondly, we monitor their blood sugars carefully, sometimes in conjunction with an expert who manages their diabetes, whether it's their primary care provider or maybe even an endocrinologist. But typically we will with time taper down the Dexamethasone and it makes it a little bit easier, but we want patients even with diabetes to benefit from the Dexamethasone as part of their induction regimen.
All right, let's move to another question. Here's a question from Stacy at the VA, at the Veteran affairs. That asks, "Just finished stem cell transplant in July. My last bone marrow biopsy showed none of the previous 17p." I'll explain what that is in the moment. "Can a person move from high risk to low risk after transplant if their FISH profile changes?"
Well, very quickly as background, we typically divide myeloma into two categories: high risk myeloma and standard risk myeloma. About 25% of patients have what we call high risk myeloma. And there's lots
of different definitions, but the one that Stacy's referencing here is something patients often call the 17p or the 17p deletion. That just means that there is a part of chromosome 17 and all of our chromosomes have a P arm and a Q arm. That's where we get the phrase, "Mind your Ps and Qs," if you're old enough to remember that. The P arm is deleted, and so there's a gene there that's missing. It's called the P-53 gene. It's kind of an important gene. And when that is deleted, then the cancer can be a little bit more aggressive. And that's one of the ways we define high risk. So Stacy's question is if she was high risk before her transplant, but now we don't detect that abnormality, has she been, if you will, downgraded to standard risk?
Unfortunately, we don't really think of it that way. I'm glad to see that it's disappeared because the burden of myeloma is down, but that patient is typically considered to be high risk from then on. By contrast, people can go from standard risk to high risk over the course of myeloma, and that's part of the challenge of myeloma. It can evolve over time and become more aggressive. And one of the ways we look for that is also the phrase that Stacy used, FISH, or fluorescent in situ hybridization. It's a big fancy word. It just means make sure your doctor has gone fishing. What I mean by that is we fish for or we look for certain genetic abnormalities when we test someone's bone for multiple myeloma.
All right, let's move to another great question from Brittany in Ohio, who says, "What would you recommend for a diet in multiple myeloma?" I have to say this might be the most asked question when we do a Q&A with Dr. Joe, and there isn't really a perfect answer. Sometimes we talk about myeloma and we talk about the immunoglobulins or the proteins that it makes. People wonder if there's some kind of special protein diet for myeloma and there really isn't. We do know that there is a connection between obesity and cancer in general and in particular myeloma as a risk factor. So we're very careful to talk to our patients about balanced diets and ensuring that their weight is appropriately managed. But there really isn't a perfect myeloma diet. Obviously everyone has different opinions around this and we want to respect the difference of view and preference of people's eating habits.
But I would particularly emphasize just a couple of things. A balanced diet, as we've said, as recommended by multiple different dietary organizations. In myeloma in particular, we want to make sure our patients stay very well hydrated because of the risk of kidney involvement with multiple myeloma. And then thirdly, being aware of the fact that when patients are on Dexamethasone, it can increase the appetite. So expect and understand that someone's appetite might change a little bit while they're on Dexamethasone. Thanks for that question, Brittany. That was great.
Here's another question from Angela who said, "I had an auto or autologous stem cell transplant. Would it be best to get bone marrow from a healthy person?" It's a really fascinating question and really an important concept for us to think about for a quick moment. So most of our patients in multiple myeloma who are so-called transplant eligible or we feel can go through the stem cell transplant process, get stem cells from themselves.
That's why we call it auto. We collect from patients stem cells and stem cells are really just cells that come from the bone marrow that are like seeds that could grow a new bone marrow. So we take those stem cells out, then we give the patient the high dose of chemotherapy that we want to help get rid of their myeloma with, and then we give them their stem cells back. That's called an auto transplant. I've obviously simplified it for us. The reality is though, however, that those stem cells gave rise to myeloma once. And so when we do an auto transplant, it's not curative. It often puts myeloma in remission for a long time, but the disease will come back. Theoretically, if we could get stem cells from someone else who's healthy, typically a sibling that might match a little bit better, we could have better outcomes in myeloma.
The reality is, historically we've learned that this is very hard to do in myeloma and very, very few patients really benefit from what we call the allotransplant when you get it from someone else. We do
allotransplants in leukemia and lymphoma and other conditions, but we rarely do it in multiple myeloma. It may be considered in very special circumstances. Great question again from Angela.
Here's one from Natalie that says, "Should a patient with multiple myeloma and amyloidosis be treated by an amyloidosis specialist or a multiple myeloma specialist?" That was a great question. For those who may not be familiar, amyloidosis is kind of a cousin disease to multiple myeloma. Well, first of all, there's actually about 30 different types of amyloid. But the one kind of amyloid that's most common in North America is called AL amyloid. And the L refers to light chains because these patients have plasma cells in their bone marrow, just like in myeloma, that make an abnormal protein, in this case a light chain that goes through a conformational change and deposits in an organ.
So to answer this question, I would quickly say that most of us who spend a lot of time doing myeloma also see amyloidosis and vice versa. Now, there are some people that have really hyper differentiated into becoming a amyloidosis doctor or just a multiple myeloma doctor, but we tend to see both. And it really depends on the patient because most patients will either predominantly have myeloma and may have some component of amyloid or predominantly have amyloid, but meet criteria for myeloma, it's not so much that we think of them as two separate diseases together. They're very much connected. But it does reflect, I think, an important principle that we've often shared at the IMF, that when someone has a relatively rare condition like myeloma or amyloidosis, it's very good to be in touch with an expert in that field.
Our community oncologists take wonderful care of our patients, but they also care for all sorts of different tumor types. And with the rapid evolution of multiple myeloma and amyloidosis, it's good to have a connection to a myeloma expert. And we at the IMF can help find you one if you don't have one already.
All right, let's move yet to another great question that says, "When people relapse, does it happen aggressively or slowly?" And the reality is from this great question that Terrence asked, is it can be either. This is one of the challenges of myeloma, is that every patient is unique and is different with myeloma. Sometimes we think of it as multiple myeloma because it has multiple different ways of presenting itself. Sometimes it can grow back very, very quickly and sometimes it can grow back very slowly. Sometimes what we call biochemical relapse, where we just see little changes in blood tests over a long period of time before it grows back. And this speaks to the importance of that ongoing communication with your healthcare team, getting those blood tests done because we want to catch it in the blood before you feel anything.
But also sharing any symptoms you may have that could indicate a relapse with excessive fatigue or bone pain or a change in your bowel habit or in your urinary habit. So these are the kinds of things that we want to look for and that we monitor in patients who have received treatment and have gone into a certain depth of response before the disease relapses. So that's all the questions for today. We hope they were helpful to you, but please feel free to ask many more of them. You can always go to our media channels and use the hashtag #AskTheIMF and we'll be happy to answer your questions. Don't forget also to subscribe to our YouTube channel for the International Myeloma Foundation so you can be up-to-date with the latest information.