Welcome to The MDS Sessions brought to you by the Video Journal of Hematological Oncology (VJHemOnc). This exclusive discussion features leading experts Amer Zeidan, Anne Mwirigi, David Gomez-Almaguer, Mariana Guaraná, Rishi Dhawan and Iman Abou Dallé who discuss some of the differences and challenges faced in their countries in managing myelodysplastic syndromes (MDS).
The topics of discussion include the epidemiology, diagnosis and treatments used for MDS around the world.
“Traditionally, MDS has been thought, in the Western world at least, as a disease of older patients. Statistics, basically, point to MDS happening most in patients in their 70s. The median age is 71 to 76, with most of the patients, 80 percent, being 65 years and older. Studies have suggested that in some countries like Far Asia, many of the MDS patients are younger, in their 40s and 50s. And not much actually is really known about the epidemiology of MDS in the other countries.”
– Amer Zeidan
“So, I’m the same category as some of my colleagues here whose countries do not have as yet properly developed epidemiology databases for hematological malignancies. So, I would have to rely purely on my practice and anecdotal data. The first thing I would say is that MDS, to me, is rare even in comparison with other hematological malignancies.”
– Anne Mwirigi
“Well, in some centers like my center or in big cities, we have, I think, everything. It’s just a matter of money sometimes, but we have everything including we have next sequencing generation. But the majority of patients who are not in big cities or in big centers are diagnosed by the old way. It’s the refractory anemia without any other cause and based mostly in morphology, aspiration and biopsy, excluding other diseases.”
– David Gomez-Almaguer
“Diagnosis of myelodysplastic syndrome is difficult for most of the centers. The main reason is that clinical hematology and hematology services are still restricted to big cities. So, majority of India, the smaller cities don’t have access to good hematopathology, as well as clinical hematology. And at AIIMS, diagnosis of MDS, like majority of other centers in country, is morphology based. There is very limited access to good quality cytogenetics and genomics.”
– Rishi Dhawan
Treatments for MDS around the world
“So, this is one of the biggest problems because, again, it depends if your patient is on private or public hospital. So, if the patient has insurance, that’s okay. Probably, they will get like lenalidomide or EPO or hypomethylating agents and probably, will go to transplant earlier. But if you are in public hospitals, and I can say that most of the centers in Brazil are public, you have a big problem because we don’t have hypomethylating agents for all, just in a few centers. EPO is also difficult to get for these patients and is very expensive to pay so they can afford using EPO for long time.”
– Mariana Guaraná
“So, in Lebanon, we do have all the approved drug for MDS. There is accessibility for growth factors, hypomethylating agents, lenalidomide. They are all covered by insurance and by the public health as well. We do have access to luspatercept with a single patient request form. So, it needs to be requested on a patient name. We do have venetoclax for AML treatment, but we can still use it high-risk MDS patients and select patients, of course. There is little access to clinical trials, but we do sometimes participate in a few clinical trials. We are currently recruiting patients for the Stimulus and the MDS-2 trial.”
– Iman Abou Dallé
Amer Zeidan Hello, everyone. Thank you for joining us for another episode of MDS sessions, and Happy New Year. We’re hoping for a better 2021 for everybody, and it’s a pleasure to have this episode where we go from the traditional discussion of new drugs and novel mechanisms of action into some of the challenges that are experienced by MDS patients across the world. And it’s really a pleasure to have some investigators from across the world, basically, with me today.
Amer Zeidan My name is Amer Zeidan. I’m an Associate Professor of Medicine at Yale University and the Director of Hematology Early Therapeutics Research. And I’m pleased to be joined in alphabetical order by Dr. Anne Mwirigi, who’s a consultant hematologist at the Aga Khan Hospital in Nairobi in Kenya, and Dr. David Gomez Almaguer, who’s the Head of Hematology Service at the Hospital Universitario, UANL, in Monterrey, Mexico and the Chair of Council of the International of Hematology, as well as Dr. Mariana Guarana from the Hemorio Institute in Rio de Janeiro in Brazil.
Amer Zeidan Dr. Rishi Dhawan, who’s an Assistant Professor of Clinical Hematology in the All India Institute of Medical Sciences in Delhi, India. And last but not the least, Dr. Iman Abou Dallé who’s a hematologist/oncologist and an instructor of Clinical Medicine at the Naef Basile Cancer Institute in the American University of Beirut Medical Center in Lebanon. So, really, a very prestigious and geographically varied group of investigators. Thank you so much for joining us today.
Amer Zeidan So, we’ll get to it. I think I would love to start by getting your sense on the epidemiology of MDS in your countries. Traditionally, MDS has been thought, in the Western world at least, as a disease of older patients. Statistics, basically, point to MDS happening most in patients in their 70s. The median age is 71 to 76, with most of the patients, 80 percent, being 65 years and older. Studies have suggested that in some countries like Far Asia, many of the MDS patients are younger, in their 40s and 50s. And not much actually is really known about the epidemiology of MDS in the other countries.
Amer Zeidan So, I wanted to get your sense if there are any studies that you’re aware of from your countries but also your clinical sense of how often do you see these patients with MDS. Maybe, I can start with Dr. Iman Abou Dallé and go around.
Iman Abou Dallé Thank you for the question and the introduction first. So, unfortunately, in Lebanon, we do not have a national cancer registry that’s updated and it usually relies on passive reporting from oncology physicians. And MDS is usually lumped with other leukemia cases. We cannot really specify the MDS incidence.
Iman Abou Dallé However, there was some personal effort from our institution, in 2015, we conducted prospective nationwide epidemiological data registry over a one-year period. And this usually estimated an incidence of 0.71 per 100,000 habitant, which is somehow lower than what’s reported in the Western countries. Probably, like you said, probably, it can make sense because our population is younger, but the median age was around 73. So, it’s still occurring in older patients. And of course, we have to keep in mind that is not a registry, where it’s a study that might represent some under-estimation or patients were not diagnosed early on or not included in the study that we did a few years ago.
Amer Zeidan Dr. Almaguer?
David Gomez Almaguer Oh, yes. In Mexico, we have a different presentation of neoplastic disease. For example, acute lymphocytic leukemia is similar or a little higher than myeloblastic leukemia. The median age of myeloblastic leukemia is 44, 45 years. And still, we’re a young country. Therefore, we have an estimate of three to six MDS patients per 100,000 inhabitants. That’s more or less.
David Gomez Almaguer As other not well-developed countries, we don’t have that perfect statistics to mention. So, my numbers are not really exact nor precise, but I can say this is more or less what we have seen here, three to six for 100,000 inhabitants and the age, median age, about 65 years old. It’s a little younger than in other Western countries.
Amer Zeidan Dr. Guarana?
Mariana Guarana Hi, everybody. Thank you for this discussion. So, the first challenge from you, when I tried to look at the information about epidemiology in Brazil is that it don’t have any data about epidemiology. So, I know that we have a Latin American Registry that has been in progress since 2017 but so far, we don’t have any studies about our epidemiology. And when I think about Rio De Janeiro, I know many institutions here, and I don’t know anyone who has a registry going on.
Mariana Guarana So, maybe now, I have an idea to start the registry maybe in Brazil or maybe in Rio, just to start. So, we don’t have the data.
Amer Zeidan Dr. Dhawan?
Rishi Dhawan Yes. In December 2019, first week, we had our national hematology conference in India in which we presented MDS data from AIIMS. And from January 2017 to December 2019, we had 217 patients diagnosed with myelodysplastic syndrome. Of this, the median age in our cohort was 51 years and 60 percent of patients were males. Out of these 217 patients, 181 patients had no fibrosis in the marrow and 36 patients had fibrosis in the marrow. So, essentially, our dataset compared the features of non-fibrosis versus fibrosis in bone marrow in myelodysplastic syndrome, and I’m quoting figures from this data.
Amer Zeidan And Dr. Mwirigi?
Anne Mwirigi Thank you very much. So, I’m the same category as some of my colleagues here whose countries do not have as yet properly developed epidemiology databases for hematological malignancies. So, I would have to rely purely on my practice and anecdotal data. The first thing I would say is that MDS, to me, is rare even in comparison with other hematological malignancies.
Anne Mwirigi So, in my practice, I would probably see one MDS patient for every, you know, five to 10 combined acute leukemia patients. The second thing I will say is I agree that the incidence seems to be in quite young patients, from the ages of 30 all the way to 70. Although this will be covered in the next question, sometimes, you wonder whether we are missing on some bone marrow failure syndromes in younger patients due to our inability to carry advanced testing.
Anne Mwirigi So, I would say I don’t have numbers that give a proper estimate for my country, but in my assessment from my practice, it is rare and it does occur in younger patients than expected from the West.
Amer Zeidan Yeah. I think this is all very interesting. I think there is a general agreement that MDS, similar to the Western world, is generally quite rare as a blood cancer. And I think the fact that the median age might be a little bit lower in some of the resource-limited countries, since many of the patients are older, this might reduce the absolute total incidence. But I think when you take it as age-adjusted, I wonder if that would be along the same lines.
Amer Zeidan And I think this brings up an important point. Now, that we have a lot of, I think, increasing interest in MDS as a disease with many new therapies, maybe collaborations between pharma and investigators in different countries can help establish some registries, because I think there is a lot of interest in reaching more patients so they can benefit from the new therapies.
Amer Zeidan And following on the point that Dr. Mwirigi mentioned, which I think was also even in Western countries quite an issue, is the under-diagnosis of MDS because it occurs generally in very older patients. Nobody wants to have a bone marrow biopsy, especially back when we did not really have any active therapies.
Amer Zeidan And I wonder in terms of diagnostic challenges, and maybe again I can start with Dr. Abou Dallé and go around, how does the diagnostic process work? Like how easy it is to get cytogenetics or molecular data or to get a good pathologic review of the dysplasia? Do you review the marrow yourself or is there a specific hematopathologist? So, maybe you can walk us through the diagnostic process of MDS patients.
Iman Abou Dallé Sure. So, basically, it depends on the patient if he’s presenting to a primary care physician in the community versus coming to an academic institution. So, there is definitely delays in diagnosis when a patient presents through a family doctor or to a primary care physician since they have probably sometimes mild cytopenias and then they delay the bone marrow biopsies, et cetera.
Iman Abou Dallé However, these patients who are presenting to an academic institution probably will be offering bone marrow aspirate early on and biopsies. We usually do it ourself as a procedure, and then we have a hematopathologist that reads these biopsies. We do have cytogenetics. We do have as well the FISH testing, and we do DNA extraction in case there is any underlying disease that we can then add on molecular studies for later.
Iman Abou Dallé The NGS myeloid panel has been introduced two years ago in our institution and we use it basically in difficult cases where we cannot establish a MDS diagnosis from morphology, sometimes for prognostication or for therapeutic care implications. But we have to keep in mind that NGS is still not covered by our national or insurances. So, the patients need to pay out of pocket for these tests and these are expensive, especially with our economical status. So, there is a lot of patients that they might need help, and we usually do offer them from our cancer fund to fund these testing, if necessary.
Iman Abou Dallé I want also to say that majority of patients, like two-third of them, usually they are referred to us when they are at high risk, having excessive blast or they have refractory cytopenias, et cetera. And then definitely, these patients were diagnosed delayed in their disease course.
Amer Zeidan But it sounds like you have access to cytogenetics, like karyotype and FISH in almost everybody, if I understood correctly.
Iman Abou Dallé Yeah. Yes.
Amer Zeidan How about in Mexico, Dr. Almaguer?
David Gomez Almaguer Well, in some centers like my center or in big cities, we have, I think, everything. It’s just a matter of money sometimes, but we have everything including we have next sequencing generation. But the majority of patients who are not in big cities or in big centers are diagnosed by the old way. It’s the refractory anemia without any other cause and based mostly in morphology, aspiration and biopsy, excluding other diseases.
David Gomez Almaguer Of course, we have seen mistakes like liver cirrhosis or something like that simulating that kind of problem in the center with more technology. But I think that about 50 to 60 percent of Mexican patients are not really, really good quality of studies. In the big center, we have this. So, this is the problem in a large and big country like us. It’s about 120 million, and I insist about half of the population maybe are diagnosed by the old way to do for it.
Amer Zeidan How about in Brazil, Dr. Guarana or in Rio de Janeiro?
Mariana Guarana Yes. When we talk about diagnostic process, the first thing is the difference between private and public hospitals. So, if you work in public hospitals, the resources are scarce. In my institution, we have karyotype and we perform morphology and bone marrow biopsy. However, we have to send the bone marrow biopsy for other laboratories. So, we don’t have a hematopathologist in our institution.
Mariana Guarana So, we meet the patient, and the first problem sometimes is the delaying for the patient to get into the Hematology Department. For many times, we receive patient with symptoms like for six, seven, one-year symptoms of anemia. So, when they get into the hospital, sometimes, they are already transformed to acute myeloid leukemia. And the patient with the MDS, we can perform bone marrow biopsy and karyotypes, but we lack training in the laboratory. So, many times, we don’t have the result of the karyotypes.
Mariana Guarana So, I think that the main problem is, sometimes, we don’t have training for the people in the laboratory and sometimes, we don’t have resources because NGS also in public health in Brazil is very difficult, just in private hospitals. And also, in private hospitals, you have to pay for NGS because it’s not covered by insurance. So, it’s very different if you are in private hospitals or in public hospitals.
Amer Zeidan Yeah. I think like an important aspect connected to this, maybe I can ask you to touch base on this with the next treatment when we talk about treatments, is the nature of the insurance system in your country, because I wonder if the difference between private or national insurances and what does that mean in terms of availability of whether it’s diagnostics or therapeutics.
Amer Zeidan So, Dr. Dhawan, how is the diagnostic process in India?
Rishi Dhawan Diagnosis of myelodysplastic syndrome is difficult for most of the centers. The main reason is that clinical hematology and hematology services are still restricted to big cities. So, majority of India, the smaller cities don’t have access to good hematopathology, as well as clinical hematology. And at AIIMS, diagnosis of MDS, like majority of other centers in country, is morphology based. There is very limited access to good quality cytogenetics and genomics.
Rishi Dhawan Even at our institute, we have to outsource these tests to private laboratories. And essentially, when we outsource it, we don’t have a very good control over asking them for a review. For instance, even though the cost of cytogenetics, the conventional karyotyping in India is… In dollars, it is 75 to $100 per test. So, it is still cheap against American standards. But if not enough metaphases are observed by the lab, it is very difficult to convince the patient to shell out again funds for a repeat testing at these labs. So, that is one example.
Rishi Dhawan And with regards to next generation sequencing, it is also not very expensive. It is 200 to $300 per NGS panel. However, we don’t have control over the bioinformatics, the calling of variants. So, many times, we feel stumped by the report. So, we still rely essentially on morphology. However, if the patient is very poor, cannot afford anything, then the minimum we ask is to try to convince them to get a FISH for deletion 5q. At least that would give them access to a generic lenalidomide, which is very, very cheap and has gratifying results as we all know.
Amer Zeidan Yeah. A couple of years ago, I actually gave an MDS talk through the American Society of Hematology in Indonesia, and I had the chance also to visit in Sri Lanka. And talking to colleagues over there, they mentioned, I think, along the same lines of what you’re saying. So, there is availability to do karyotype, but it’s very limited and expensive. So, you have to be selective. You cannot send it in all the patients.
Amer Zeidan And I’m getting the same sense. I think next generally sequencing is even a challenge in some parts of the US. But I do think karyotype should be, hopefully, part because it’s very integral to not only diagnosis clearly but also for risk stratification.
Amer Zeidan Dr. Mwirigi, how about in Kenya?
Anne Mwirigi Yeah. So, in our position, first of all, to come to the bone marrow biopsies, for many years, it has been kind of sub-optimal having access, obtaining access to good pathology services around the country. So, the Kenya Association of Pathologists along with the East African Association got together and piloted a program where they trained pathologists and physicians outside of the capital to perform bone marrow tests.
Anne Mwirigi So, now, we have a situation where bone marrow biopsies are performed in most major sectors of the country, and they can then be referred to hematopathologists in the center for reporting. So, that has been a major improvement within the last few years. However, we do not have the facilities in the country to perform any cytogenetics or next generation sequencing for any patient.
Anne Mwirigi So, even in my service where I might see MDS patients, unless I’m suspecting an MDS at the outset, it is relatively quite unlikely I will send off cytogenetics, which I have to send overseas. Because if you do your bone marrow aspirate and then see the morphology to be dysplastic and you’ve captured your cytogenetic sample, you could run it the next day in your lab. But in our setup, the only samples we get to send off, we send off to India and we send them once a week.
Anne Mwirigi So, if you’re thinking you have an MDS, you kind of have to do the test on the one day of the week and instead of the patients who pay just $150, they then have to pay another 200 or $300 on top of that for the sample to be sent to India. So, I think you can see for MDS, it becomes a little bit of a challenge stratifying these patients outside of what we can see morphologically, and what their TAMs are doing, and their age, and things like that. It is on rare occasion that an MDS patient gets cytogenetics done, and we don’t have next generation sequencing.
Amer Zeidan Yeah. And these are all alike. Speaking to many colleagues across the world, unfortunately, this is not, I think, very unique to Kenya. As we’re just saying, I think this access to karyotype is actually quite challenging in many countries, which I think is important to try to improve care for these patients.
Amer Zeidan So, I think on the next set of questioning, I will start with Dr. Mwirigi and go in reverse order. I want to discuss just connecting to the same, as we start talking about treatment, the issue of blood transfusions. You know, blood transfusions, many MDS patients are regularly transfused and it’s an integral part of the treatment. I think it could represent big challenge in some countries to do that in a regular fashion. Also, connecting that to the insurance and how those patients pay for transfusions and its availability in routine basis.
Amer Zeidan So, maybe I can start with you, again, Dr. Mwirigi and go around.
Anne Mwirigi Thank you. So, with regards to blood transfusion, it really is a divide between public and private sector patients. Not long ago in the middle of COVID, we had a major blood shortage in all the public sectors in the country. So our national blood bank was empty, and we tend to have the situation where everyone in National Blood Services has to do a replacement donation. So, you can’t get a transfusion unless you bring a donor.
Anne Mwirigi The private health sector seems to be significantly somewhat better. But on the private side, the costs rack up quite high and it is very hit or miss whether you get insurance to cover transfusion, because insurance tend to, you know, decide to maybe only pay for inpatient procedures, but then won’t pay for transfusion as a day case, and so on and so forth.
Anne Mwirigi I think another challenge from a transfusion perspective is our transfusion in private sector is quite expensive because we don’t have NAT testing. So, we test each sample as if it’s a patient sample. So, for instance, your hepatitis B, HIV, hepatitis C, malaria will all be done separately and so, they’re very costly tests. So, at the end of the day, the cost of a pint of blood to the patient is very high.
Anne Mwirigi That being said, patients put together their money, their insurance, their donations from relatives, and then come for, you know, four weekly transfusions and we do carry on with it. We do get a challenge with iron chelation because that’s very expensive again. And for patients who don’t have insurance, it becomes a balance between, “Am I going to get transfusion? Am I going to get chelation?” So, for the transfused patients, it’s a little bit of a short-lived process, and I tend to try to move to medication because, you know, most of the time, by the time I get to trying to chelate them, we run out of money. Yeah.
Amer Zeidan Dr. Dhawan, how about transfusions in India?
Rishi Dhawan The situation is quite similar to Kenya, when I listen to Dr. Mwirigi. So, patients have to, again, get transfusion only if they replace the unit for the blood as well as platelets, and universal leukodepletion is not available in India. Approximately, 30 to 40 percent of centers still give whole blood transfusion to the patients, and irradiated blood product facility is not available in most of the centers outside big institutes and big private sector hospitals.
Rishi Dhawan Plus, at our institute, we transfuse around 1,500 transfusion sessions every year in our day care. And as a result of this, there is, you know, competition for resources between patients with thalassemia, aplastic anemia, and myelodysplastic syndrome, and patients with acute leukemias like ALL who are on outpatient therapy. So, effectively, this limits the access to blood transfusion for transfusion-dependent myelodysplastic syndrome patients at our center as well.
Rishi Dhawan So, transfusing them optimally to maintain a good quality of life as is recommended above 80 grams per deciliter of hemoglobin, most of the patients are unable to achieve that. And their hemoglobin very frequently hovers between 5 to 8 grams per deciliter when we see them in the clinic.
Amer Zeidan How about in Brazil, Dr. Guarana?
Mariana Guarana So, in Brazil, we have this system public health. So, it’s not so difficult to get blood transfusions if you need and if you are receiving medical care in Hematology Department. So, if you have insurance, you can have blood transfusions like, covered by the insurance, but if you are in a system public health, the problem that we have is, I think that it’s the same around the world, is with donors. In my institution, we also have good center of hemotherapy. So for, frequently, we perform campaigns to get more donors. And if you are treating a patient with MDS or acute leukemia and other malignancy, it’s not difficult to prescribe a blood transfusion because this is covered by the government.
Amer Zeidan Dr. Gomez?
David Gomez Almaguer A transfusion is not really a big problem in my country, as about 80 percent have access to transfusion all over the country. A chelation is not easy to give, and it’s about 20 percent of the patients in need will receive chelation. But transfusion is not really a big problem, in general, in our country. That’s a good situation and of course, we try to get donors but usually, emergency transfusions are provided, in general, in our country. It’s about, I think that 70, 80 percent of patients will get easy transfusions in our country. All right?
Amer Zeidan So, you don’t have that replacement system where the patient has to bring relatives or friends to donate?
David Gomez Almaguer Yes, but usually it’s, how can I say it, the surgeons ask for blood and usually, that kind of blood are not really used, you know. So, in big center, usually, we have more blood and that’s the way we are doing because the surgeons are asking for blood just to be sure that if something happen. Usually, the problem is not really happening. So, we have some blood but yes, we try to… We don’t have a lot of free donors, usually related donors in our country.
Amer Zeidan How about the cost of the blood? Does the patient, is it covered completely by the insurance, or does the patient have to pay their cost on-
David Gomez Almaguer It’s about 80 percent, 70 percent of the people are covered one way or another, but the cost is not too high. To get a transfusion here in Mexico, it’s about $150, sometimes 200. It depends on the institution, but about 70 percent, 60 to 70 percent, of the people have access to transfusion almost free. Almost free.
Amer Zeidan That’s great. Dr. Abou Dallé, how is it in Lebanon?
Iman Abou Dallé Yes. In Lebanon, so most of the patients have access to blood transfusions and it’s covered by most of the insurances and also, the public health. However, we do not have a central national blood bank. So it’s usually, we do have blood banks from Red Cross, from NGOs and from institutional blood banks where they usually rely on direct donations, like from friends and family, et cetera. The big challenge is for platelet transfusions because they usually really need some relative or friends to donate platelets. And especially during the lockdown in the COVID-19 pandemic, so we had a shortage in blood units and it was a real challenge.
Amer Zeidan How about the issue of the irradiation and the leukodepletion, is that quite routine in Lebanon or is that also a challenge in terms of-
Iman Abou Dallé Yeah, we do have this in our institution. In big institutions, there are many but in small community hospitals, they need to refer patients to other bigger institution for irradiation and leuko induction.
Amer Zeidan That’s good to know. So, I guess in the last… Go ahead.
Rishi Dhawan I still have one more comment. Sorry to jump in again.
Amer Zeidan Sure.
Rishi Dhawan Another challenge I need to put forth is that most of the patients are unable to get definitive treatment and they continue on lifelong transfusion support, and then they develop allo antibodies, alloimmunization. And then it becomes another big challenge to give them least incompatible blood transfusion for support. So, this is one more challenge which I forgot to mention.
Amer Zeidan Yeah. No, unfortunately, it’s a common problem in MDS patients, especially in the more advanced forms of disease. So, I guess, as we start to go into last part of the discussion today about treatments, maybe we can talk about among like the standard treatments like ESAs, hypomethylating agents, lenalidomide, what are currently is available in your countries and how is it? Is it relatively difficult to get those drugs and how many of your patients are being treated or not?
Amer Zeidan Maybe I can start with Dr. Gomez and go around.
David Gomez Almaguer We are more prone in the… We’re androgens fans, danazol, mesterolone, et cetera, and we have published that information. And we usually go to androgens and couplet with EPO, erythropoietin, at least in the not really high-risk cases, right. In the high-risk cases in my institution, we really go rapidly to transplant with that. With that, we have experienced use in haploidentical and with also allogeneic or all kind of allogeneic.
David Gomez Almaguer The cost of a transplant in my institution is about $15,000 in allogeneic. Therefore, it’s cheaper for us to provide a transplant to treat the patient for a long time. And with that, of course, 10 to 20 percent of the population in Mexico have access to azacitidine or lenalidomide, just usually private insurance because the national insurance system, it will not pay for that kind of drugs. So, it’s a few patient will be treated with that kind of expensive drugs. Therefore, we try to transplant everybody in the high-risk patients and we use androgens and EPO in the low risk. And what can I say?
David Gomez Almaguer In my personal opinion, dealing with private patients, you know, azacitidine or something like that, it’s just like a fantasy for a time, is my experience. They improve sometimes but for a while, and then they are in blastic crisis or they’re transforming or they’re dying and you cannot transplant anymore. So, I usually go to transplant rapidly. And if I use hypomethylating agents, it’s just for a while and just for the time we get the donor. And with the haplo world, haploidentical transplantation, we’re doing a lot because that’s changed the general way to do transplants, allogeneic transplant. That’s what I have to say.
Amer Zeidan That’s great, and I think somewhat similar to what many countries or resource-limited countries do with CML, where we have very good therapy but it’s lifelong and very expensive. And, you know, sometimes, you choose to go with transplant because it’s more cost-effective for the system.
Amer Zeidan How about in Brazil, Dr. Guarana, the issue of the availability of treatments and ability to use them for patients?
Mariana Guarana Yeah. So, this is one of the biggest problems because, again, it depends if your patient is on private or public hospital. So, if the patient has insurance, that’s okay. Probably, they will get like lenalidomide or EPO or hypomethylating agents and probably, will go to transplant earlier. But if you are in public hospitals, and I can say that most of the centers in Brazil are public, you have a big problem because we don’t have hypomethylating agents for all, just in a few centers. EPO is also difficult to get for these patients and is very expensive to pay so they can afford using EPO for long time.
Mariana Guarana Even when we use EPO in the public health, we only have the percentage of 4000 units. So, it’s really hard. And new agents, in general, I think that it’s impossible when we never discuss this because we don’t have clinical trials. And sometimes, we just have transfusions to keep the patients alive until the transplant. Even in this COVID era, it’s been really hard to get the patients into transplant. So, what are we seeing is that many patients are transforming to AML or dying of MDS because they need a lot of blood transfusions so you have the problems with this. So, it’s not easy and sometimes, I’d like to mention, sorry, we use thalidomide with EPO.
Amer Zeidan Yeah. And this innovation I’ve seen with androgens or thalidomide. How about in India, Dr. Dhawan? Do you have access to those, I guess, standard but expensive therapies or do you try to innovate and use like low-dose intensity chemos or try to work with it to transplant, if possible?
Rishi Dhawan So, let me start first with medical treatment and then move on to transplant. India is very fortunate because there is abundance of generic drugs, and multiple generic options are available for erythropoietin, lenalidomide and hypomethylating agents. For instance, average cost per month for lenalidomide is US dollars 40 to 50 only, and azacitidine per month cost is around US dollars 400.
Rishi Dhawan So, to begin with, most of the patients are able to afford. However, compliance is a problem as it is self-funded or limited government grant available per patient in our institute. And our institute is one of the largest and most well-funded institute in India. It is an institute of national importance, so it is relatively easy for patients to access to government funds.
Rishi Dhawan If we write and give an estimate to the patient and they apply, they get the funding. Most of them do get the funding. However, the problem is the lag time between the application, then collection of documents. Then the patient submits it to the government authority for approval, then the fund is granted. And then ultimately, it is credited into AIIMS account. That takes up time. Average time is, I guess, anywhere between three months to five months.
Rishi Dhawan Hence, treatment is often not continued beyond one to one and half years or maybe two years for most of the patients. And then there is slow onset of response with these treatments. That is also an issue. So, financial fatigue is a phenomenon we see very often. And another problem is long-distance travel for periodic evaluations in the clinic and then there is lack of access to clinical trials or access to newer agents, like luspatercept or isocitrate dehydrogenase inhibitors, et cetera. That is with regards to medical treatment.
Rishi Dhawan Then the access to hematopoietic cell transplantation in India is limited and the facility is restricted to three to four public sector teaching hospitals in the country. There are private hospitals that do carry out transplants. However, because of the finances involved, it is beyond the reach of most of the lower class and middle-class Indian population.
Rishi Dhawan Just to give you an idea of some figures, between 2012 to 2019, around 400 allogeneic transplants were done in India, of which nine percent were done for myelodysplastic syndrome. As Dr. Gomez mentioned, transplants, either self-funded or government grant, average cost of sibling donor allogeneic transplant in India is around 25,000 US dollars. However, the challenge for us at AIIMS is the long interval between symptom onset and diagnosis, and then the long interval between diagnosis and transplant. By the time patient arranges funds or we get access to government grant for the particular patient, a lot of time has elapsed.
Rishi Dhawan As a result of this, most of our patients, even if they don’t progress to accelerated or the blast phase of their disease like EV1 moves to EV2 or EV2 develops AML, there is a high burden of infections and they develop other comorbidities due to transfusional iron overload. So, by the time the transplant is sequenced for a particular patient as part of not their disease, not only their disease criteria, but the patient fitness criteria also is compromised.
Rishi Dhawan Haploidentical donor and unrelated donor transplants are low in India. For instance, approximately 2,000 transplants are done in India every year, of which 16 percent are haploidentical and only five percent are matched unrelated donor transplants. And there is data, which has been published from individual centers, that these are associated with higher transplant-related mortality and morbidity as compared to what is observed from the centers in the West.
Amer Zeidan Now, that’s very comprehensive. Thank you so much. Dr. Abou Dallé?
Iman Abou Dallé Yes. So, in Lebanon, we do have all the approved drug for MDS. There is accessibility for growth factors, hypomethylating agents, lenalidomide. They are all covered by insurance and by the public health as well. We do have access to luspatercept with a single patient request form. So, it needs to be requested on a patient name. We do have venetoclax for AML treatment, but we can still use it high-risk MDS patients and select patients, of course. There is little access to clinical trials, but we do sometimes participate in a few clinical trials. We are currently recruiting patients for the Stimulus and the MDS-2 trial.
Iman Abou Dallé And for the transplant, we do have three transplant units in Lebanon. They are basically in the capital of Beirut, and we do perform allogeneic stem cell transplantation mostly for intermediate to high-risk patients or even in relapsed low-risk patients, and it’s basically match-related. We do have the haploidentical as well. It’s much costly than India and Mexico. It costs around $80,000 and we do rely on the comorbidity score rather than the chronological age. So, we can transplant up to 70 years old. Yeah, that’s all.
Amer Zeidan Dr. Mwirigi, how about things in Kenya?
Anne Mwirigi Yeah. So, when it comes to treatment, I would say this is where our national health funding came into its own just a few years ago because most of these patients would have no access to treatment. But now, you can apply for cancer treatment and get the treatment on a month-to-month basis.
Anne Mwirigi Interestingly, in terms of MDS treatments, and thanks to the generics that come from India, you will find that in Kenya, cheapest to most expensive goes lenalidomide is the cheapest at $150, followed by transfusion of two units per month is about $250, followed by ESA which is about $400, followed by hypomethylating agent azacitidine which is about $550 per month. So, that’s the range of treatments available for a vast majority of patients.
Anne Mwirigi And Kenyans tend to treatment-thinking patients. So, once you get them started and they believe in the process, they will keep coming. And as soon as the National Health is funding them, they’ll keep going. If they developed a more advanced MDS or they’re not responding, then that is the point at which we would refer them for transplantation and the referral is usually to India because it’s the most affordable. And obviously, the whole build-up to that is quite advanced. It’s quite engaging.
Anne Mwirigi Now, in the private sector, patients who have access to very good insurance can have the branded Revlimid and the branded Vidaza. But in some of those patients, it’s worthwhile because of the cost of these drugs, to refer them directly for stem cell transplantation when they have a donor, just because it’s just as expensive over the cost of just maybe two years to do the drugs on their own. And that’s just about how we do it in Kenya, yeah.
Amer Zeidan Yeah. That’s very informative. We’re coming to the end of the discussion and really, this is extremely informative. I think it’s really like we’re expecting a lot of the difficulties and the challenges, but at the same time, it’s really good to know that there is availability in most countries to some of the active agents, whether they are generics and in different formats and also, the relatively affordable prices. Of course, we need to do a lot more to allow more, especially for clinical trials and transplant.
Amer Zeidan Sorry, Dr. Dhawan. You want to say something? Rishi Dhawan Yeah. And many times, it forces you to innovate. So, like we mentioned in the previous part of the talk, our transfusion challenges. Although there is no data, but what I have now recently started doing for patients for whom giving them periodic platelet transfusions is a challenge because of donor access and sequencing them in our day care to get transfused. They are needing maybe every week or multiple times a week platelet transfusions, and the ladies are struggling with menorrhagia.
Rishi Dhawan So, I have requested the gynecology service to put hormone-releasing intrauterine contraceptive device like Mirena to them, and that has improved quality of life because the alternative is to keep them on oral contraceptive pills, but then there is only… You can’t keep them for months together on that. Every month, their hemoglobin goes down, then their blood transfusion requirement is a issue along with platelet transfusions. So, that is something which we have now recently started doing more and more often for the ladies. And we are collecting data and after some time, we’ll get together and see how it turns out.
Amer Zeidan Yeah. Innovation is always very important. There’s so much to discuss. I really would love to have you all again in a subsequent discussion more about some of those innovations and other ways to do this. And hopefully, it would be a COVID-free world and hopefully, in few months. Thank you so much again for being with us today, and Happy 2021 to everybody. Thank you so much.
Iman Abou Dallé Thank you.
Anne Mwirigi Thank you.
Rishi Dhawan Good luck. Bye-bye.
Amer Zeidan Bye-bye.
David Gomez Almaguer Thank you, everybody. Nice to see you.