Chronic Leukemia Q+A - Fall 2023
Program held November 2023
Physician experts addressed patient and caregiver questions on a variety of topics, including treatments, side effects, watch and wait and more.
Speakers

Adam Kittai, MD
The Ohio State University

Nicole Grieselhuber, MD, PhD
The Ohio State University

Watch the video (captioning included)

Chronic Leukemia Q&A
Wednesday, November 29, 2023
Dr. Adam Kittai, The Ohio State University Comprehensive Cancer Center
Dr. Nicole Grieselhuber, The Ohio State University Comprehensive Cancer Center
Kevin Radelet:
We're honored today to have two esteemed panelists, Dr. Nicole Grieselhuber and Dr. Adam Kittai are both assistant professors in the division of hematology at the Ohio State University Comprehensive Cancer Center. Dr. Grieselhuber attended medical school at Washington University in St. Louis and completed her residency in internal medicine and fellowship at Ohio State in hematology and also in oncology at Ohio State. While she is an expert in all forms of hematology, she is particularly well-versed in CML, which is great for today's Q&A session.
Dr. Kittai specializes in treatment of chronic lymphocytic leukemia, CLL and Richter syndrome. He attended medical school at the Sackler School of Medicine at Tel Aviv University, did his residency at George Washington University and fellowship in hematology and oncology at Oregon Health Sciences University.
They're both members of various professional organizations including the American Society of Hematology, the American Society of Clinical Oncology, and the American Association for Cancer Research. So please welcome Dr. Grieselhuber and Dr. Kittai. Thank you both for joining us today.
Dr. Nicole Grieselhuber:
Oh, it's a pleasure to be here.
Kevin Radelet:
Well, we're going to kick it off and get right to it. I guess a general question to start is can you explain the difference between chronic and acute leukemias?
Dr. Adam Kittai:
I'm going to give this one to Nicole because I think her disease specialties span both acute and chronic.
Dr. Nicole Grieselhuber:
Thank you, Adam. So there's a lot of different ways of classifying leukemias, so they're all cancers of the blood. And one of the major ways that we think about them are one, what type of cell within the blood has become cancerous? And so broadly speaking, we think about myeloid and lymphoid malignancies, just reflecting the specific origin of the cell that has become cancerous. So I'm more of a myeloid expert and Dr. Kittai is more of a lymphoid expert.
And then within each of those categories, there are leukemias that develop very suddenly, very quickly over a period of weeks. And often patients are quite ill when they first present. And typically the acute leukemia is, it's a very immature cell in the bone marrow that has become cancerous. In chronic leukemia it's whether they're myeloid or lymphoid, it's a more mature cell that accumulates in the blood, in the bone marrow. And so those cancers don't tend to present quite aggressively. Not the patients can't have difficulty with the disease or its treatment, but it tends to be a much slower presentation and particularly in the CLL patients, sometimes people may live with their cancer for many years and not need any treatment.
Kevin Radelet:
Okay. Are there any new and effective treatments for CLL?
Dr. Nicole Grieselhuber:
I'm going to give this one to Adam.
Dr. Adam Kittai:
I'll take that one. Yeah, so there's always exciting developments within chronic lymphocytic leukemia. So I think the two new agents that are likely to be approved for the treatment of CLL in the next year are pyrotinib, which is a new kind of BTK inhibitor. And lisocabtagene maraleucel, which is the type of CAR T-cell therapy that you may have heard about a lot in the news. And so these are two agents that we're really excited about having in CLL that we expect to be approved in the next year.
So pyrotinib and liso-cel are both likely to be approved after someone has received one of the approved BTK inhibitors, ibrutinib, acalabrutinib or zanubrutinib and venetoclax, the BCL-2 inhibitor, which is really an area of unmet need for patients with CLL because we don't have good or effective therapies currently approved in that setting. And both of these drugs have shown really good efficacy and really work after patients use those two frontline agents.
Kevin Radelet:
Great. Same question for CML. Are there new and effective treatments that are out there?
Dr. Nicole Grieselhuber:
Yes, there are. And so CML is very fortunate. So they're actually at the moment six tyrosine kinase inhibitors that are approved for CML treatment in the US. There is also a seventh drug that has a different mechanism of action that is not a kinase inhibitor. Already, there are a lot of treatment options for patients. Four of these drugs are approved in the frontline setting, meaning the first drug that patients take. The most recently approved one is a drug called asciminib, which has a different mechanism of inhibiting the BCR-ABL protein.
And it's been approved for patients that have developed resistance to other CML therapies, particularly those that have a certain resistance mutation, but it's currently being studied for newly diagnosed patients in the hopes that it may perhaps work better to get the CML under control. And it might be better tolerated in it. So those studies are ongoing and I think that that's very exciting.
The other area that's quite new in CML, we have learned in probably the last five years or so, five to 10 years, that there's a population of patients that can actually safely stop their TKI if their BCR-ABL PCR has been very low or undetectable. And so that's another area that I think is really exciting for patients to know that they're not necessarily committed to taking a medication for life.
Kevin Radelet:
Okay. Dr. Kittai, a question on CLL. Is there a significance in a substantial decrease over the last year in the vitamin D level of a patient diagnosed with CLL about a decade ago? The patient has not been under CLL treatment but has been taking in anti-allergy medicines to thwart serious allergic reactions.
Dr. Adam Kittai:
I would say that vitamin D being low is not associated with CLL, it's not associated with treatment to CLL. Having your vitamin D at a higher level using supplements is something certainly that you could talk to your primary care doctor about. There are a lot of different ailments that are associated with having a low vitamin D, so I do encourage my patients to take supplements to increase their vitamin D level, but it's not an essential component to patients with CLL, it's not associated with the disease or treatment.
Dr. Nicole Grieselhuber:
I'm going to, I guess jump in and make one comment. I think this raises a important issue for any patient with a chronic leukemia, whether it's CLL or CML because fortunately many patients with chronic leukemias live for a very long time. It's very important that patients do all of their routine medical care. So checking vitamin D levels would fall into that. But also things like blood pressure, if you have diabetes, having that under good control, cholesterol being under good control, getting other cancer screenings like mammograms, colonoscopies at the appropriate ages, all of those things are important.
And I think sometimes people can get very focused on the cancer, but it's equally important to manage all of the other medical conditions or prevent medical conditions that are not related to the cancer in order to really treat the whole patient.
Dr. Adam Kittai:
And also on that note, making sure that you maintain your exercise regiment so you're physically optimized in order to get treatment. And also having a good round diet is also very important because as Dr. Grieselhuber just mentioned, some patients put that aside to focus on the cancer. And as if you're living a long time, you really have to make sure that you're taking good care of yourself and we often forget about that. The other thing I always tell my patients is the healthier they are going into treatment, the better they're going to tolerate treatment and the better they'll do overall.
Kevin Radelet:
In regards to diet. Are there certain foods that they should avoid?
Dr. Adam Kittai:
Nothing in particular. So I do recommend the Mediterranean diet just because there's a lot of data out there about how it has good effects on cardiovascular risk and a lot of our drugs in CLL can affect your heart. So overall, I think just a good solid, well-rounded diet is the best for you. I will say that there are certain foods that can't interact with medications, specifically grapefruits, and we talk about Seville oranges. So if you are taking a drug for your cancer, you should ask your pharmacist if there's some foods that you should avoid because it can interact with the ability to absorb the medication as well.
Kevin Radelet:
Okay. What is the latest treatment and research on treating CMML? The patient is currently being treated with the Vidaza four days a month every four weeks.
Dr. Nicole Grieselhuber:
So I can definitely take this one. So CMML is chronic myelo monocytic leukemia. And so this is a chronic leukemia that is very different and distinct from CML and really in my mind is an unmet need. So in this leukemia specific type of blood cell called monocytes, accumulates in the blood and the bone marrow. Patients similar to CML often have enlargement of their spleen, sometimes will have more systemic symptoms like fevers, night sweats, weight loss and that sort of thing. It's a comparatively rare leukemia and historically it was lumped in with other types of blood cancers in clinical studies. And so Vidaza or the generic name is Azacitidine, is a fairly standard treatment for myelodysplastic syndromes and for elderly patients with AML, acute myeloid leukemia. And CMML got roped in and included with those studies. So Vidaza and decitabine are fairly standard treatments.
The unfortunate thing is that less than 40% of patients will actually respond to that. And the number that have a remission is about half of that. And so clearly there's a need for better treatments. In the last 10 years, there has been a real move in the field to have specific studies for CMML, just those patients. And there have been just in the last couple of years, some precision medicine studies that have opened where there's an attempt to match patients based on the genetic markers of their cancer. And so clearly there's a lot of work to be done, but I think that the field is really recognizing that patients with CMML really deserve to have the same attention in terms of clinical trials and the same targeted treatment options that the other leukemias do.
Kevin Radelet:
Okay. Back to CLL. This is a lengthy question, but what's the latest research on taking drug holidays from ibrutinib for CLL? The patient has been on the drug for almost five years. Mild side effects, dosage gradually reduced at the patient's request to 140 milligrams a day. White blood counts normal and steady, but after five years with some side effects and with the dosage gradually reduced to the 140 milligrams, is there still a good reason to switch to acalabrutinib?
Dr. Adam Kittai:
So that is a loaded question with a bunch of different things that we can talk about. So I think let's talk about drug holidays and when to switch to the second generation BTK inhibitors. So in terms of drug holidays, there's been some good research that shows that patients who stop a BTK inhibitor, who have good disease control can be off therapy for two years. And I have some patients who've gone further than that as well. I think it really depends on how good the disease control was when the patient stopped the drug. Typically, I really try to get at least a year in if not two before considering stopping. And I really don't stop unless someone develops a significant adverse event. So in general, I still recommend continuing the BTK inhibitor if at all possible. But if someone has to stop because of an adverse event and their disease is well controlled, I usually quote my patients around two years that they could probably be off therapy for.
There was a recent study that was presented at our international workshop for CLL conference a few weeks ago that was out of the British group that looked at patients who stopped ibrutinib after being on a median time around six years. And the vast majority were still not needing treatment after a year or two after stopping. So drug holidays, coming off therapy for adverse event is certainly something that you definitely could do.
Now in terms of dose reductions and when to squish to a second generation BTK inhibitor, in general, if someone's on ibrutinib and they require a dose reduction, I don't dose reduce anymore, I just switch them. And the reason why I just switch them is for two reasons. Number one, there's good data that shows that patients who are dose reduced for their ibrutinib do worse. So it's really important to maintain the dose of 420 if at all possible.
And the other set of data that is important is that now that we have two phase 2, phase 3 trials that show that our second generation BTK inhibitors, acalabrutinib and zanubrutinib are safer than ibrutinib. So in general, someone needs to stop ibrutinib for a toxicity or needs to dose reduce for a toxicity, I usually just go ahead and switch them to the acalabrutinib or zanubrutinib. And they usually tolerate one of those two drugs just fine.
And so in general, the summary point here is that it's okay to have a drug holiday. Usually patients can last for around two years off of drug if they have good disease control when we stop. And have a very low threshold to switch to the second generation BTK inhibitors for patients who are on ibrutinib, especially if they're requiring a dose reduction.
Kevin Radelet:
Great. Are there long-term side effects from Calquence?
Dr. Adam Kittai:
Yeah, so the long-term side effects of the BTK inhibitors are pretty much the same throughout all the different classes, with some of them having more of a higher prevalence for these side effects than others. So the main side effects I watch out for, or the main side effect I watch out for is hypertension. So hypertension is the only side effect that increases over time with the BTK inhibitors. And so really paying close attention to your blood pressure, having high blood pressure over a long course of time can really lead to significant cardiovascular disease, especially for these patients who were on these BTK inhibitors for years.
The other side effects that we watch out for which don't tend to increase over time but still have a incidence about the same for every single year that you're on it are going to be atrial fibrillation, easing bruising and bleeding and joint pains. And so in general, those are not cumulative toxicities. They can occur at any time. Typically, they occur within the first year or two of therapy, but I have seen late occurrences as well. But hypertension is the big one that I really try to attention to for patients who are on the acalabrutinib, zanubrutinib or ibrutinib over time.
Kevin Radelet:
Can you share with us who decides what mutations are tested for in myeloid panels?
Dr. Nicole Grieselhuber:
So that's a very, I guess broad question. And the mutations in myeloid malignancies, that could easily be an hour long talk in and of itself. And so I think that there's different panels. Some institutions like OSU have their own in-house testing panel. There's a variety of commercial labs that oncologists in the community may send out their patient's blood or bone marrow for those tests. I would say at this point the field has really settled on, there's probably about 50 mutations that we commonly test for in myeloid malignancies in general. I don't know that it's quite as important for CML, for CMML. That information does give us some idea about how aggressive the patients' leukemia is likely to be.
And I think also this is very much a moving target. And so there may be mutations that at this point in time we don't really know how they affect the prognosis or there's no medication specifically targeting them. As soon as either of those things change, the mutations that are not commonly looked for start to be incorporated.
So this is something that is a continual process in the field of deciding what are the important genes to look at.
Dr. Adam Kittai:
There's something else to add on that too. It actually is date specific to some extent as well. So for instance, in Ohio there's a certain law, if I'm correct, that basically states that insurance companies will pay the same for testing for one mutation as they do for 50. So that's why at OSU we have all of our mutational panels are all 50 genes, and those are specifically picked by our hematopathologist as being the most important within the specific disease that we're testing in.
And so whenever either me or Dr Grieselhuber put in the order to test these [inaudible 00:23:39] panels, we specifically state what the disease is that the patient has in order to select the right panel that's specifically created to test. But I know other states don't have a limitation in that way and they can test up to 300, 400 mutations, but as Dr Grieselhuber said, some of these mutations we don't even know what to do with, and we're not even sure if they're actionable or if they matter In terms of a patient's prognosis.
Kevin Radelet:
Can you UMRD be achieved even after a dose reduction in venetoclax as part of V plus O?
Dr. Adam Kittai:
Yeah. So I'll tackle this question, and I think this might be actually a pertinent question for CML too in terms of patients who need dose reductions in getting to a molecular remission. But in terms of CLL, the regimen of venetoclax plus obinutuzumab is given for one year in the frontline setting. And how it was designed in the clinical trial was to give it for one year. And the question here is, can patients get undetectable measurable disease, which means that we're unable to detect the CLL using the modern detection labs that we have, if they have a dose reduction in the Venetoclax. I would say that we don't really have great data on this. We do have good data about dose reductions and not as good outcomes with BDK inhibitors, but we don't have as much data for venetoclax.
Anecdotally, I've had some patients who do reach undetectable minimal residual disease even with a dose reduction for venetoclax. So I think it's important to try to maintain the max dose of Venetoclax at 400 milligrams if at all possible. But if a dose reduction is needed, a dose reduction is needed. Because remember, the reason why we're dose reducing somebody is because they're having a toxicity. And
if you don't reduce the dose, you may have to stop the drug altogether and it's better to continue the drug at a lower dose than it is to stop the drug altogether.
And once again, some of these toxicities can be dangerous. And so we're always weighing the balance of maintaining the treatment dose and the toxicity that it might induce. So I would say direct answer to the question is that yes, I've seen it. I can't say whether or not there's a decreased rate of undetectable minimal residual disease with a dose reduction, but if you need a dose reduction, you need a dose reduction. And the reason is for safety.
Dr. Nicole Grieselhuber:
And I can address the same issue with CML if there's time for that?
Kevin Radelet:
Go ahead please.
Dr. Nicole Grieselhuber:
So in CML, the effectiveness of the treatment is tracked by the BCR-ABL PCR. So this is a genetic test that measures to a very fine degree how many of the cells in the patient's blood carry the BCR-ABL mutation. And there are very specific published guidelines about what's considered an adequate or not adequate response to treatment. And the timing at which we expect that a patient should hit those milestones, and it actually takes a year and sometimes longer for many patients to hit the target of what we want that level to be.
There are many patients that I have seen that for whatever reason, had toxicity with their TKI and had to dose reduce. And with CML, because we have this ability to track the BCR-ABL level, my personal philosophy is that if that disease marker is at goal, whatever amount of the TKI that the patient is taking is working for them. We honestly in medicine have I think an incomplete understanding of the differences in how individual patients metabolize drugs, what the level of the drug is in an individual's body.
And so well, we don't start at a reduced dose if somebody is getting good disease control at a reduced dose and they're tolerating it better, I think that's perfectly fine. And I'll also say I have reached out many times when I've had CLM patients with unusual complications of treatment. To a Dr. Brian Druker who's at Oregon Health Sciences University where Dr. Kittai trained who's really a world expert in CML, and he's quite interested in investigating whether for CML patients, it may be preferable once the disease is under control to drop the dose of the drug and try and preemptively avoid toxicities. So I think there's a lot of fine-tuning that can be
done, both in terms of general treatment guidelines, but also at an individual patient level.
Kevin Radelet:
After a year of VENE+OBIN, I achieved MRD, but my blood counts are still low. Is that normal?
Dr. Adam Kittai:
Yes, that's normal. So some patients, so the majority of our patients with CLL are older. And when you're older, your bone marrow unfortunately is responsible for creating your cells, your blood cells. And when you're older, after you've completed a therapy, sometimes it can take a long time for the bone marrow to fully recover and it might not fully recover at any point. And so actually within the CLL world, someone can have what we call a complete response, which means that we can't detect the CLL anymore with incomplete marrow recovery, meaning that they're not producing their cells like a normal person would. And so it's a very frequent thing that we find with patients with CLL that after they've completed therapy, they might have low cell counts.
Dr. Nicole Grieselhuber:
I'm going to make one comment about this. So many of the myeloid leukemias, not just CML, but AML and MDS are also more common with age. And so the same age group of patients that tends to get CLL, also tend to get other types of leukemia.
And while it is true that many cases of CLL patients that have low blood counts after finishing their treatment, it's just that the marrow takes a while to recover. I have seen a good number of patients that actually ended up having two different leukemias or two different types of blood cancer more broadly, and have shared some patients with my CLL colleagues at OSU or with other colleagues at OSU that specialize in lymphoma or myeloma. And that can be a real challenging situation.
And so I think that it is important if somebody's cancer are taking an unusually long time to investigate that and make sure that there's not something else going on.
Dr. Adam Kittai:
And to that end, in order for someone with CLL to have a complete response with incomplete marrow recovery, you have to have a bone marrow to make that assessment. So it's like if you are having, for cell counts, you probably should talk about potentially having a bone marrow biopsy, depending on how low the cell counts are.
Kevin Radelet:
Okay, my CLL transformed to DLBCL stage 1, germinal center subtype. It's been a year since I completed six rounds of RCHOP and 18 radiation treatments. My latest scan continues to show a complete response. What should I watch out for and what should I suspect for in the future?
Dr. Adam Kittai:
It's a really complicated question. So what this patient has is something called Richter's transformation, which is really an area of unmet need for patients with CLL. In patients with Richter's transformation, it's a really difficult disease to treat, so if anybody has Richter's transformation, you definitely be seen by someone who specialize in CLL to get a second opinion to see what they would say. And the reason why I say that is that oftentimes when someone gets into a complete remission with their Richter's transformation, I do recommend an allogeneic stem cell transplant because there's a high risk of relapse without it.
Now, there are certain cases where we don't recommend a transplant, for instance, if someone is older or if they have what we call not clonally related disease. And so what that means is that you can either have a diffuse large B-cell lymphoma that just so happens to happen in somebody with CLL. Or you can have CLL that literally turns into diffuse large B-cell lymphoma. In the cancer world, when anything turns into something else, that's never a good thing. And so when it turns into the diffuse large B-cell lymphoma that's clonally related. And those patients do much, much, much worse than those patients who are not clonally related.
The problem is that the not clinically related, which is the good type, is the minority of patients, about 10 to 20% of patients. And so this is a conversation that they should have with their hematologist oncologist whether or not a transplant would be necessary. And also consider a second opinion just to talk with somebody who has seen a lot of these CLL with Richard's transformations. In terms of what to look out for really is symptoms, so making sure that you're keeping track of your fevers till weight loss, night sweats or fatigue that come back, or if any big lymph nodes come back too.
Kevin Radelet:
Okay. This one is, you hear it in the media quite a bit, but are shingles and RSV vaccines appropriate for chronic leukemia patients?
Dr. Adam Kittai:
I'm going and start with CLL and then call Nicole for CML. So in terms of shingles, so we used to say no shingles because it was a live virus vaccine, but now it's an activated virus. And so for shingles in general, I tell my patients to get it if they're motivated to get it. For the most part, if someone's had a history of shingles or chickenpox, I say, "Go ahead and get it." It really to help prevent shingles, which is really a nasty side effect in anybody. In terms of RSV, the data is still pretty new. As a group, we've decided to recommend the RSV vaccine and the only reason why we decided to recommend it is because patients with CLL are immunocompromised, and in general we tend to favor giving vaccinations and not giving vaccinations.
But the recommendation is not the strongest because we really don't have very good data for patients with CLL to get this RSV vaccine. And so we don't know how well patients with CLL are responding to the vaccine. And so I think that if you're somebody who's around a lot of little kids, if you are somebody who goes to a lot of crowded events and you have CLL and you're older, an RSV vaccine would be something that I would recommend. But I would say that is a controversial statement that is not universal amongst the CLL world.
Dr. Nicole Grieselhuber:
So I'll answer this for CML patients. So CML patients I think are not near as immunocompromised as the CLL patients, particularly if their CML is under good control. The BCR-ABL level is very low or undetectable and their blood counts are relatively normal. So while I do encourage my patients to get vaccines that are recommended really for anyone of their age group, so that includes things like the pneumonia vaccine for older adults, the shingles' vaccine for older adults, we don't really have specific guidelines for CML patients getting different vaccinations than anybody else.
This is something that I think is different if a CML patient has more aggressive disease that's really behaving more like an acute leukemia, that's a separate conversation. But for the vast majority of CML patients, we encourage people to get to the same vaccines that they would otherwise.
Kevin Radelet:
Do you know if Medicare Part D covers drugs needed for treatment?
Dr. Adam Kittai:
Complicated question too.
Kevin Radelet:
They've done their homework.
Dr. Adam Kittai:
No, I honestly don't really know how to answer that question. Usually for patients with Medicare Part D, we put the drug through to see if it's approved, and then we work through it if it's not. I guess one way we can answer this question too is as Kevin had mentioned at the beginning of the program, the Leukemia Research Foundation, along with a lot of the other organizations that help patients with leukemia, have a lot of different grants to help actually with even medications. And so what you can do if your drug is not covered through your insurance is you can reach out to some of these various organizations to see if there's grants that can help you cover the cost of the drug. And also the drug companies usually have some grants too that can help patients cover the cost of drug if that's necessary too.
Dr. Nicole Grieselhuber:
I echo everything that Dr. Kittai said. So it's no secret that all of these medications, whether it's for CML or CLL, are expensive. And so I generally don't have problems with people being completely unable to get their medications. I think that there's a lot of different paths for people to get medications, whether it's through their insurance, through these grant companies, the drug companies that make these drugs often have assistance programs. And I think the key is for me, I've found partnering with a good pharmacist, a good social worker, OSU is very fortunate. We have a whole team of people that investigate these different options, and so it's uncommon that we can't get somebody the medication that we need. It just can take a lot of jumping through different hoops.
Kevin Radelet:
Right. Is there any research on differences in progression or response to treatment of chronic leukemia is based on gender?
Dr. Adam Kittai:
Not that I'm aware of. In general, male patients tend to do worse than female patients, but that's an overall population issue. And I don't think it's related to the actual leukemia.
Dr. Nicole Grieselhuber:
Not that I'm aware of for CML. And I will say that because outcomes for CML patients fortunately are really quite good right now with the modern TKI therapies. To the extent that there are some studies suggesting that for most CML patients life expectancy is not different than if they didn't have CML. And so that makes it really hard to study a difference in outcomes when patients already do for the most part really well.
Kevin Radelet:
Okay. What are some of the triggers or red flags, if you will, for moving a patient from watch and wait to treatment?
Dr. Adam Kittai:
Yeah, so this is a CLL directed question. So oftentimes with patients with CLL, they get diagnosed incidentally, meaning that you were feeling fine and then you go to your doctor, they do a blood test and they find that your white blood cell count is high and that's how you get diagnosed. There were a lot of studies that were performed in the early or the late 90s that showed that patients who got treatment before they had an indication to treat, actually did worse than if we waited until they had an indication to treat.
Now that paradigm is now being retested with our new drug, so that might change, but right now we wait until somebody has an indication to treat before we start therapy and that usually can take years. And there are about, then there's a subgroup of patients who will never need to be treated. And indications to treat are going to be symptoms. And those include significant fevers, chills, weight loss, night sweats, fatigue, a low hemoglobin, a low platelet, big, big spleen and big lymph nodes. But if you don't have those indications, we usually keep patients on watch and weight until they do meet those indications. There are some other rare things
that can happen that can lead to us to start treatment, but they're rare and they go on forever.
In general, I like to call it active surveillance as opposed to watch and wait. And the reason why we call it active surveillance is because if someone doesn't require treatment now, they remain off treatment. They are less immunocompromised typically because they haven't received treatment, which sometimes can make you more immunocompromised. And by waiting, you are waiting and allowing other drugs to be developed, which are typically safer and more effective. So active surveillance is a nice way of thinking about it because you were fighting your cancer by actively surveilling it by waiting to get treatment.
Kevin Radelet:
Okay. Do you differentiate at OSU, I guess the question is on bone marrow transplants, do you have a hard no at some particular age?
Dr. Adam Kittai:
I can answer it, but Nicole probably sends more of her patients to transplant than I do, so I'll add on to something if she has [inaudible 00:41:19].
Dr. Nicole Grieselhuber:
Yeah, so I think the first thing to understand is that even if a program says that there is an age cutoff, by definition, those are always arbitrary. And so here at OSU, the typical number that I quote for patients is 75. I will say it is a very rare 75-year- old that is healthy enough, fit enough, has few enough other medical problems that they can get a bone marrow transplant. But we have done it. We actually send all of our patients that are getting evaluated for transplant that are age 60 or older to a specific geriatric oncology clinic where they do a comprehensive assessment of the patient's global functioning. So this includes things like nutrition. The physical therapist assesses their strength, their balance, their hearing is assessed, and all of these things we know impact patient's outcomes.
They also will assess the patient's cognitive abilities. If somebody has some cognitive impairment that perhaps has not been recognized, that can really impair their ability to manage a complicated treatment plan and taking different medications. And so I think the decision always has to be individualized for patients.
I also think that it's important for people to understand if just because transplant is an option for a given disease does not necessarily mean it's the right option for every patient. I encourage my patients if they're going to see a transplant doctor, to
really listen to how it's presented, what the treatment entails, and there are some patients that will hear what that path would look like and will say, "You know what? This just sounds too much for me at my age and I would rather enjoy the time that I have with less aggressive treatment, and not be in the hospital for a month getting a transplant." Which is frequently what that entails.
Kevin Radelet:
Okay. A patient has a ferritin level of 1100, should they be concerned?
Dr. Adam Kittai:
Not typically, no.
Dr. Nicole Grieselhuber:
I think it's something that really depends on the context. So ferritin is a marker of inflammation and so it can go up, if somebody has an infection or any number of other medical problems. For my patient population, the myeloid leukemia patients, some of the CMML patients have needed transfusions a lot. And so sometimes the ferritin going up is a sign of iron building up in the body related to having a lot of transfusions. And so in that context it might be something that I pay attention to that triggers looking into if there's iron overload, that's something where there are specific treatments and also specific consequences related to the patient's overall health if it's not addressed. But by itself, just that number, it's hard to say if it's something that any one person should be concerned about.
Kevin Radelet:
Okay. Here we have a patient who had a bone marrow transplant three years ago and they're now dealing with GVHD. Is there anything new to help with this?
Dr. Nicole Grieselhuber:
Yes, there is. So I can definitely take that one. And I will preface this by saying, well, I did some training in transplant as part of my fellowship. I am not, at least at OSU, a transplant doctor. We have in recent years split to our myeloid leukemia and transplant groups into two separate groups. But with that grain of salt, I will say that in recent years there have been a number of new treatments for GVHD. So for anyone on the call that hasn't heard of this, this is a disorder where the patient that had a bone marrow transplant or stem cell transplant, the donor immune system attacks the recipient's organs. And this can cause a lot of complications, can really affect people's quality of life after a transplant, even if the leukemia is gone.
Steroids are really the mainstay of treatment, and in years passed, other immunosuppressive drugs were used and a lot of times these were adapted from the rheumatology world, other autoimmune diseases, but now there's increasingly studies of drug specific for GVHD. So I'm going to list a couple that have been approved in recent years. So Ruxolitinib has been approved to treat both acute and chronic GVHD that hasn't responded to steroids. A drug called ibrutinib, which I think many of the people on the call are familiar with because it was first aid in CLL has actually been approved to treat chronic hit GVHD.
And then most recently there is a drug called Belumosudil. This is an inhibitor of a protein called ROCK2. And that's for patients with chronic GVHD that have not responded to two or more treatments. I think the other thing that is important in the transplant field, and this may not be as relevant to the person asking this question since they already had their transplant, but in the field in general, we think prevention is much better.
And so there's a lot of work being done on better ways to prevent GVHD from happening in the first place. And this includes things like manipulating these specific cells that are transplanted to avoid giving people the cells that cause GVHD. And also other medications given as part of the transplant process to try and prevent GVHD. So I think that there are a lot of new options, a lot of new exciting research.
Kevin Radelet:
Okay, for a chronic phased CML in an otherwise healthy 33-year-old female who would like to plan for pregnancy, is it accurate to plan TFR in two to three years or more? Or three to four years for newly diagnosed? She understands that everybody's different, but are there other considerations as well in pregnancy planning?
Dr. Nicole Grieselhuber:
Yeah, so this is a great question and I think this really gets to the heart of individualized medicine and treatment. And so for younger patients, with CML frequently there's a great desire to get the CML under good control. So then a couple of years people can go off of the CML medication, whether it's in order to conceive and have a child or for any number of other reasons. I think that the most important thing is one, the patient has to be very motivated to adhere to taking the TKI. That's the number one thing is that you can't be missing doses and saying, "I forgot my medication today." And then two days later I was busy and I took it late and that sort of thing. And so that's the number one step.
The second thing that we really consider is that the second generation TKIs, so these are drugs like dasatinib and nilotinib and bosutinib get people to a PCR that's at goal much quicker than imatinib. And so picking a medication that has a better chance of getting someone to that target is really key. And then I think the other thing that happens in these situations is there is an element of competing demands here. And so I definitely have seen women in their 30s where they feel that the biological clock is ticking. And so while it's not ideal, sometimes people will come off of their TKI when their level is not quite where we ideally want it to be because having a child is important.
There was a large study that came out of Europe several years ago where they followed a bunch of women with CML and found that the prognosis of the women with CML that stopped their TKI to conceive and then to have a pregnancy was really not different than other CML patients. With a couple of caveats, one being that their CML was under good control before they stopped. And two, that when they were not pregnant, that they had good adherence to taking their medication. And so I think there's a lot of ways that the hematologist and obstetricians can work together to allow women with CML to be able to do the things that they want to do with having a family.
Kevin Radelet:
What is the status of Radotinib? Are any of the, is it a promising treatment?
Dr. Nicole Grieselhuber:
So I'll be perfectly honest, when I saw this question, which was submitted before this session, I actually had to go look this drug up. So this is a tyrosine kinase inhibitor that was developed in South Korea. It is chemically very similar to Nilotinib and it seems to have similar efficacy. In other words, the same spectrum of activity and the same effect on CML that's resistant to Imatinib, if Nilotinib works, Radotinib works.
The studies that have been done on this have been relatively small and really only done in Asia. So the drug is only approved in South Korea. I will say that there is a current phase 3 ongoing that is open in some other countries in Europe, also in China. I have not heard anything about the company wanting to pursue studying this in the US and I think really because it's so similar to Nilotinib. There's not a ton of excitement for that particular drug. And I think some of the other newer TKIs that work a little bit differently, the field is much more excited about those.
I'm not saying it's by any means a bad drug. I think sometimes there are business decisions that the pharmaceutical companies make in terms of where they're going
to focus their money in terms of developing drugs. And I think this drug probably through no fault of its own ended up on the losing side of those kind of business decisions.
Kevin Radelet:
Okay. We have a 83-year-old patient who's been on 100 milligrams of Calquence for over two years, but his joint pain has become pretty difficult to deal with, and wonders if there is a lower dose available or appropriate?
Dr. Adam Kittai:
So unfortunately 100 milligrams per day is the lowest dose available for acalabrutinib. Now, there was a recent study that looked at patients who switched acalabrutinib for an adverse event to zanubrutinib. And a lot of those patients were able to decrease the severity of the toxicity they were experiencing on acalabrutinib. So in general, the thought in the field is that if somebody has a toxicity on acalabrutinib, they can probably switch to zanubrutinib. That may have improvement of their symptoms and vice versa. There are some caveats to that, but that's something that can be talked about with their doctor to see a switching to zanubrutinib would be appropriate or doing a dose holiday.
So sometimes when I have a patient who has a toxicity and I'm not sure if it's due to the acalabrutinib or the drug that I'm treating the patient with, I'll do a dose hold for a week or two, to see if the toxicity improves. And if the toxicity does not improve, that tells us that it's maybe not related to the drug that we're giving them.
Another thing that we do with joint pain specifically is sometimes the joint pain could be inflammatory, like an autoimmune type of situation. And sometimes giving a short course of steroids can get the joint pain under control. But oftentimes it's not inflammatory and more of an arthritis. And unfortunately if it's really due to the acalabrutinib and the arthritic joint pain, there's not much that you can do, but you can switch over to zanubrutinib or do a dose or drug holiday.
Kevin Radelet:
Is there any thoughts or direction you might be able to offer to the patients in terms of clinical trials?
Dr. Adam Kittai:
Yeah, this is a great question. So I am one of those people, and I'm sure Nicole, Dr. Grieselhuber is like this as well, that we recommend a clinical trial if ever available. So at OSU or an academic center, we have many clinical trials available. We try to
have a clinical trial for every single patient. Unfortunately, sometimes the clinical trials can be a little bit rigid in terms of who can go on the study and who can't based off of other comorbidities. So that really can come into play where if you have significant cardiac history, it might be difficult for you to go onto a BTK inhibitor study just as an example.
But for instance, we really have a lot of trials available. We do recommend patients consider a clinical trial. Because remember when a clinical trial is developed, the point of the clinical trial is to develop either something that's safer than what we already do or better or both. And so we don't create clinical trials thinking that we're going to give the patient an inferior therapy. So that's why I think clinical trials are important.
On top of that, without having clinical trials, we can't figure out what to do next or what's better than what we currently have. And so being enrolled on a clinical trial also has a broader purpose to it in terms of the cancer community, because we're able to effectively track how that patient's doing in a monitored manner, to be able to inform us of how to do better by all of our patients in the future.
So I would say that if you're somebody that's interested in clinical trials, talk to your doctor about it. Consider going to a site that has clinical trials for your disease, because I'm always encouraging my patients to try to enroll on clinical trials if possible.
Dr. Nicole Grieselhuber:
I'll echo everything that Adam said. Really, all of the drugs that we have for leukemia and every cancer happened because patients enrolled on clinical studies. It is a time commitment often, and that's something I tell people upfront is that clinical trials sometimes require extra doctor's visits or blood tests or other things that you wouldn't be doing if you weren't on a clinical trial just because we need that information to know if the drug is safe, if it's being tolerated, if it's working for people.
And so I think it's important to know what you're getting into, but for many patients this can be a really great option. I think it also depends on the individual disease. So for example, in CML, there are currently four different drugs approved in the frontline setting. And so the impetus to be on a clinical trial for someone that's newly diagnosed is not quite as strong because there are four drugs and they work pretty well for the vast majority of patients. If somebody has had difficulty with treatment, they haven't tolerated, it's not worked for them, then there's a very strong rationale for clinical trials.
The other chronic leukemia that I talked about earlier, the CMML, that's really an area where if a patient can be on a clinical trial, I strongly encourage it, and that's just because the response rate with it, the available therapies is 40% at best and maybe only half those patients are in a complete remission. And so for those patients, we just desperately need better options and it's entirely possible that a clinical study might give someone a better treatment than what we have now.
Kevin Radelet:
Well, we are getting backed up a little bit on time here. There is one thing since we're talking clinical trials that I wanted to share with the audience, and that is our website, leukemiarf.org. That's leukemiarf.org. If you look, there's a dropdown there on clinical trials. We're very proud that we are introducing our Clinical Trials Hub, and it has all kinds of information, how they work, the myths, diversity, clinical trial, right for me. And what's most exciting perhaps is finding a clinical trial and our new online search tool.
And if you look at this search tool, it'll populate here and there's a few questions that you're asked to fill out. And what's great about this, I'm sure that many patients, and of course the doctors are very familiar with clinicaltrials.gov, which is somewhat overwhelming with all the clinical trials that are offered there. But this Leukemia Clinical Trials hub is specific only to leukemia. So we want to be the one- stop shop where people come for all kinds of different information and their patient and family support. But the clinical trials hub, as far as we know, is the only one that exists out there that is specific to leukemia.
And so I will be sending along with the video of today's Q&A and the transcript, I'm going to be sending the link to this, but it's easily found again on our website, leukemiarf.org. And with that, I'd like to thank Dr. Kittai and Dr. Grieselhuber for their time today. We covered a lot of questions. Apologize if we didn't hit on all of them, but we did the best we can and we appreciate the time that they took out of their day to spend with us today.
There'll be more webinars and sessions similar to this coming up in the months ahead and all the patients out there, you'll be hearing about that. Again, if you haven't signed up, shared your email with us, you can do that on our website as well. But we thank you both again for your time, for your expertise, and thank everybody for attending as well.
So everybody have a great day. Hopefully the sun is out where you're at, and you'll have a good weekend as well. Thank you both.