What does the diagnosis, Intermediate-Risk MDS mean? Learn from Myelodysplastic Syndromes expert, Dr. Swapna Thota, in this recording.
Leigh Clark: 00:00 Hi, everyone. This is Podcast for Patients, with the Aplastic Anemia and MDS International Foundation. I'm Leigh Clark, Director of Patient Services, and I'll be moderating the podcast today. Our podcast series is brought to you with special thanks to the generous support from our patients, families, and caregivers like you, and our corporate sponsors. Thank you to everyone for supporting the series.
00:31 Today, we're going to be talking about intermediate risk MDS with Dr. Swapna Thota. She is an assistant professor at the University of Tennessee Health Science Center, and she specializes in Leukemia and bone marrow failure syndromes. Welcome, Dr. Thota. We're so glad to have you today.
Dr. Swapna Thota: 00:54 Thank you so much for the kind invitation. I'm so happy to be part of this educational podcast. It gives me great pleasure to reach out to the greater community of MDS and the caregivers and patients so we can continue to educate this group of patients to better understand their disease. Thank you so much.
Leigh Clark: 01:15 Great. So we'll start out, what is intermediate risk MDS?
Dr. Swapna Thota: 01:21 So I talk to my patients when they first have MDS diagnosis. I go over what is Myelodysplastic Syndrome and why it is called a syndrome. It's called a syndrome because every patient presents with a different kind of story. Um, for some patients, they live with low blood counts for a long time, and has just been fatigued and was incidentally detected on a routine examination and for some patients, uh, they are really sick, coming down with infections and presenting very acutely. So the stories and the natural history is very different.
01:57 I kind of give them a language of okay, to help them understand their disease and I kind of bring them to this conversation of, okay, do you understand, do you have questions about stages of disease because that's a very common terminology used in, uh, solid tumor world whether it's early stage or late stage. But in blood cancers, there's no typically staging, especially in Myelodysplastic Syndrome, as to stage one to stage four, but there is a similar terminology as risk categories based on the information of the patients, uh, of the patient's disease based on their blood counts and, uh, the information we get from bone marrow biopsies. So we use calculators to put patients into different categories, we call them risk categories and patients can fall anywhere from low to high and the middle categories is called intermediate risk category.
02:53 One of the most commonly used calculators is the Revised International Prognostic Scoring System, IPSS-R for in brief. And when the, when we plug in all the information about the percentage of blasts, the type of cytogenetics, a test we send out from bone marrow biopsy in aspirate and the blood counts when we plug all this information, and sometimes we include age as well, it spits out a risk score. When your score is between three and four point five, you fall into this category called intermediate risk category. It sometimes is referred in newer, um, calculators, especially the IPSSM calculator, describes the intermediate category as a moderately low and a moderately high category so that's another terminology people could be hearing when they have intermediate risk MDS.
Leigh Clark: 03:49 Thank you. What are the treatment options available to patients who fall into the intermediate risk MDS group?
Dr. Swapna Thota: 03:59 So once I talk to patients about, um, their risk category, they tend to quickly ask, "So what does that mean? What does an intermediate risk mean? Does that mean I'm going to respond better to treatments or not so much to treatments?" Okay? So then I take into the risk classification into somewhat of a prognostic classification, how we expect their disease to behave and we talk a little bit, if they're interested in that particular information, about their risk of transformation to leukemia, and then average survival that's is expected for somebody that your diagnosis. Once I'm done with that conversation, on an average for intermediate risk patients, this um, refers to a few years of natural history of living with this treat- with this disease. Then it brings us to the conversation of treatment.
04:54 Now, even beyond the risk category, there's a little more personalization for treatment. First of all, I, am I talking to a young patient with intermediate risk category. Any patient with MDS and having, uh, had that diagnosis in their fifth decade, in their 4th decade is considered a young patient for such a diagnosis.
05:16 So straight off we're talking about curative intent therapy such as bone marrow transplant. So, while I personalize therapy, I look at their blood counts to is this somebody who is actually asymptomatic from their disease, um, or is this somebody who is really getting transfusion dependency? What is the blast percentage that we are dealing with? Is there a need to decrease this blast percentage?
05:40 So even in this intermediate risk category, there are a certain people who behave more like low-grade MDS and there are people who tend to behave more like high-grade MDS and that kind of understanding is really critical and that's where each individual physician has to like personalize therapy based on what is happening with the patient.
06:01 If a patient is determined, especially with the new calculators of IPSS-M, that they have a moderately low, so an intermediate risk patient that tends to behave more like a low-grade MDS patient, then we focus on quality-of-life things, cytopenias that we need to alleviate so we can use agents such as Erythropoietin factors, ESA's the other terminology for it. PROMACTA platelets are on the lower end, so we try to alleviate, uh, the transfusion burden then pack up low blood counts. But if there is a higher blast percentage of a molecular path and that we are really worried about perversion and they're falling into a little bit on the higher side with IPSS-R score, if you have a score greater than three point five, you tend to behave on more of the higher risk end then we can start talking about potentially treatments such as hypomethylating agents that prevent, uh, transformation to leukemia and prolong survival of these patients.
07:01 So it's an individualization. There are several treatment options which is a good thing, so it's a conversation and a little bit of individualization of how the patient is presenting to us.
Leigh Clark: 07:13 Thank you. Are there particular challenges with treatment intermediate risk MDS?
Dr. Swapna Thota: 07:21 Historically, yes. Intermediate risk MDS it's a good thing, like I said, there are a lot of treatment options, but intermediate risk has been, um, kind of all the diagnosis that we didn't know are like really well behaving or really not so well behaving, so the low and high and everything else got categorized into this intermediate risk category. So now with the advent of IPSS-M and all this molecular knowledge that we have gained, over time we can better classify these patients into, uh, better understanding of their disease and prognosis. So one of the biggest challenges I face is that, uh, if I am treating a patient who is 62 year old, intermediate risk, he's worried five years from when he's diagnosed with MDS whether he will still remain a transplant candidate or not.
08:16 So the transplant position was a big challenge of clinicians we all face without more precise calculators. Now, with the more advanced calculators. Some of those patients, compared to IPSS or IPSSR, that are being upgraded into a higher category, there's 11% of those patients in the studies that are previously categories as intermediate that can be reclassified as those have time to behave more as high-risk. So we are able to use these calculators as to better understand the disease biology and thereby take them to transplant.
08:51 So, this, what has been a historical challenge for understanding the prognosis and what, who to put through transplant and curative therapies like that, uh, has been a little bit more dignified with the new calculators we have. So I think we're making progresses with the challenges that we had before.
Leigh Clark: 09:14 What are the risks of intermediate MDS transitioning to secondary AML?
Dr. Swapna Thota: 09:22 This is a big piece of conversation that I focus on, during conversation with the patients in the beginning meetings. I education them about MDS. Uh, a lot of people hear the term pre-leukemia and confuse that they are not really diagnosed with the cancer. And they think that AML is a true malignancy. So once we get that initial phases of, uh, trying to understand that MDS is a cancer, but could transform into a much more aggressive blood cancer called Acute Myeloid Leukemia. Everybody has a risk of this but based on which category you fall into, you have a higher chance of transforming into it. About 25, so a quarter of the patients, that fall into this, um, category of intermediate risk could technically, within a few years of their diagnosis. So it's not 100%. Uh, it's only a very small percentage. Uh, 25% I believe with the intermediate risk within a few years of being diagnosed, so three to five years of their diagnosis have a chance of transforming into a more aggressive form of blood cancer called Acute Myeloid Leukemia.
10:35 Now, if you translate that into the more recent understanding of IPS-SM categories and if we take, um, moderately low type of intermediate risk patients, like I said, they tend to behave more like the low-risk patients, so their risk is a little bit lower. Uh, so this subset of patients have about 5% transformation at one year into diagnosis. It’s a linear, uh, change as they grow into more years with their MDS diagnosis, the percentage goes up.
11:10 So somebody got diagnosed with MDS, lived with MDS, with this intermediate risk MDS for last five years, their risk goes up, um, like I said, a year into diagnosis they're 5%. Uh, five years into diagnosis, their risk category in this moderately low subset goes up to almost 10 to 12%.
11:32 So as you go through low all the way to high, the percentage increases within each category and I just shared the numbers with you for those patients that are intermediate risk, uh, by IPSS-R and moderately low by IPSS-M, and what presentations they have for transformation to AML. It's definitely one of those, um, things patients worry about and the treatments aim at delaying such transformation, including hypomethylating agents or participating in clinical trials.
Leigh Clark: 12:07 When should a patient with, who's in the intermediate risk category consider a transplant?
Dr. Swapna Thota: 12:16 So, um, like I said, several factors go into consideration because bone marrow transplant, is a pretty intense procedure so there's a patient selection, so you look at the age of patient and you look at why did the patient develop MDS? For example, there are a subset of patients that are born with genetic defects that express in their fourth and fifth decade. So if you're working with any patient that is in their fifth decade of transplant and has a score that falls into intermediate risk, that's a patient you do want to upfront talk about going through transplant. So young MDS's that fall into intermediate risk, or the MDS's that have a genetic link that they have been born with should go through a bone marrow transplant as a curative intent.
13:11 Those patients that we do not deem up front have a high risk of transformation to AML, it's a serial approach. Initially their treatment focuses on alleviation of cytopenias. Once these treatments stop working and patients become more transfusion dependent or we sense that the treatment that they're on is not doing them any good, for those kind of patients where cytopenia is an issue and there's no higher blast percentage, those are the patients that are becoming more and more transfusion dependent. We look into bone marrow transplant as an approach, uh, once they are, have seen the few low-grade MDS treatments.
13:55 If the blast percentage is increases as you do surveillance or while on treatment for these patients, um, that's another subset of intermediate risk patients that when an upfront transplant is not considered as they go through the process of their MDS and that this tends to become a little more into high grade category, that's another patient that we definitely consider for bone marrow transplant. But every patient, that falls into this category that has no major comorbidities at least an initial donor search has to be done. The timing of transplant is a big point of conversation in the care of these patients.
Leigh Clark: 14:37 Well thank you so much Dr. Thota for sharing your time and your expertise with all of us today and talking about intermediate risk MDS. If you'd like to find out more information about MDS, or other bone marrow failure diseases, you can find that information on our website, aamds.org. You can follow us on Facebook, Instagram and Twitter or if you have some questions you can give us a call on our helpline at 800-747-2820. This concludes our podcast. Thanks, Dr. Thota.
Dr. Swapna Thota: 15:15 Thank you.