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Transplantation Candidacy in MDS

Panelists: Vinod Pullarkat, MD, City of Hope Medical Center; Jamile Shammo, MD, Rush University Medical Center; Rami S. Komrokji, MD, Moffitt Cancer Center; Thomas Prebet, MD, PhD, Yale Cancer Center; Ellen K. Ritchie, MD, New York Presbyterian Hospital
Published: Friday, Feb 17, 2017


Transcript:

Vinod Pullarkat, MD:
The only curative therapy to date for MDS is an allogeneic stem cell transplant. As for the age limit, chronological age is not the only consideration for transplant. We are transplanting older and older patients. And now with the newer approaches to donors like haploidentical transplants, you have more availability of donors. Actually, there’s a donor for almost every patient, right? I just want to ask each of you about when do you refer a patient to a transplant center. When do you think a transplant is going to be imminent? Can you comment on those aspects? I’ll start with you, Rami.

Rami S. Komrokji, MD: Obviously, as mentioned, transplant is the only curative option. And the other thing, if you look at all patients with MDS today, less than 10% of the patients get that.

Vinod Pullarkat, MD: It’s the second most common indication for transplantation for un-related donors.

Rami S. Komrokji, MD: From a transplant point. But, from the disease point, like, for example, in our database, we have 3000 patients. Only 200 got transplant over the last 10 years, and we are very aggressive in referring to transplant.

Vinod Pullarkat, MD: It depends on where that patient is seen, right, and who sees the patient.

Rami S. Komrokji, MD: Right. This is even at our place where we refer almost all of our patients. So, 50% of the patients you refer to transplant are transplanted, mostly because of age and comorbidities actually, or frailty. The way we think of it, obviously, there have been several decision-analysis models looking at the timing for transplant. If a patient is high risk or has very high-risk disease, the maximum gain of survival is to send those patients directly to transplant. If we see patients with higher-risk MDS, we think of a transplant. When we see patients that are younger, lower-risk, we think that they will probably need a transplant a little bit down the road. So, I think the clear indication is the higher-risk MDS patients, lower-risk if they are younger, or potential candidates after a couple of lines therapy.

The way I discuss it with patients is it’s a benefit-risk analysis. So, you are talking about 30% to 40% cured versus 10% to 20%, unfortunately, with transplant-related mortality. And the effect on quality of life over 1 to 2 years needs some time. That’s how those decision models are based, basically, to favor early transplant or not going to transplant. I really try to put it in context for the patient. If the patient, let’s say, is 70 years old without MDS, what’s the expected survival? With MDS, what’s the expected survival? And how much will they gain in the quality of life and time, potentially? I learned over time to present that to the patient, and every patient looks at this a little bit differently, and they decide on that benefit-risk for them.

Vinod Pullarkat, MD: And I think the challenge also is to identify the lower-risk patients who have those adverse features we talked about earlier. At the end, I refer them right away.

Jamile Shammo, MD: Not to stray from your segment, but because you mentioned low-risk disease patients, I want to make two comments about the transplant piece. First is that, yes, everybody with intermediate- and high-risk disease should be evaluated in some center. And, certainly, people, let’s say, who are deletion 5q should actually have mutational analysis done because those who had p53 mutation may not necessarily have a good response to lenalidomide and may benefit from an earlier transplant evaluation. But, on the other hand, do we have enough data to suggest that people who have adverse mutational features actually are cured by transplant? And there were data from this conference that told you that the chances of relapse are higher in people who had transplant. Granted, it’s not a reason to say I’m not going to send my patient to transplant, but I think this whole science is evolving.

Vinod Pullarkat, MD: Yes. As we get more genomic data, there may be subsets of patients who may not benefit from transplant, and we should not subject them to transplant because it’s likely to be futile for those patients who have to go through all this morbidity. So, that is also a challenge. I think as transplant centers get more experience with genomic features that make a patient a poor candidate for transplant, that should be also incorporated. But, I think every patient who is a possible candidate deserves a consultation.

Ellen K. Ritchie, MD: I think so, too. Because if a patient suddenly worsens or takes a turn where you really believe that you need to transplant that patient within a reasonable period of time, unless you’ve done the homework where you’ve actually had them have the transplant consult, you’ve actually looked for a donor, you’ve actually identified a possible donor, it’s a very long period of time. So, the sooner that you actually determine whether or not a patient has a donor, whether or not you decide to go down that route or not I think is very important.

Transcript Edited for Clarity
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Transcript:

Vinod Pullarkat, MD:
The only curative therapy to date for MDS is an allogeneic stem cell transplant. As for the age limit, chronological age is not the only consideration for transplant. We are transplanting older and older patients. And now with the newer approaches to donors like haploidentical transplants, you have more availability of donors. Actually, there’s a donor for almost every patient, right? I just want to ask each of you about when do you refer a patient to a transplant center. When do you think a transplant is going to be imminent? Can you comment on those aspects? I’ll start with you, Rami.

Rami S. Komrokji, MD: Obviously, as mentioned, transplant is the only curative option. And the other thing, if you look at all patients with MDS today, less than 10% of the patients get that.

Vinod Pullarkat, MD: It’s the second most common indication for transplantation for un-related donors.

Rami S. Komrokji, MD: From a transplant point. But, from the disease point, like, for example, in our database, we have 3000 patients. Only 200 got transplant over the last 10 years, and we are very aggressive in referring to transplant.

Vinod Pullarkat, MD: It depends on where that patient is seen, right, and who sees the patient.

Rami S. Komrokji, MD: Right. This is even at our place where we refer almost all of our patients. So, 50% of the patients you refer to transplant are transplanted, mostly because of age and comorbidities actually, or frailty. The way we think of it, obviously, there have been several decision-analysis models looking at the timing for transplant. If a patient is high risk or has very high-risk disease, the maximum gain of survival is to send those patients directly to transplant. If we see patients with higher-risk MDS, we think of a transplant. When we see patients that are younger, lower-risk, we think that they will probably need a transplant a little bit down the road. So, I think the clear indication is the higher-risk MDS patients, lower-risk if they are younger, or potential candidates after a couple of lines therapy.

The way I discuss it with patients is it’s a benefit-risk analysis. So, you are talking about 30% to 40% cured versus 10% to 20%, unfortunately, with transplant-related mortality. And the effect on quality of life over 1 to 2 years needs some time. That’s how those decision models are based, basically, to favor early transplant or not going to transplant. I really try to put it in context for the patient. If the patient, let’s say, is 70 years old without MDS, what’s the expected survival? With MDS, what’s the expected survival? And how much will they gain in the quality of life and time, potentially? I learned over time to present that to the patient, and every patient looks at this a little bit differently, and they decide on that benefit-risk for them.

Vinod Pullarkat, MD: And I think the challenge also is to identify the lower-risk patients who have those adverse features we talked about earlier. At the end, I refer them right away.

Jamile Shammo, MD: Not to stray from your segment, but because you mentioned low-risk disease patients, I want to make two comments about the transplant piece. First is that, yes, everybody with intermediate- and high-risk disease should be evaluated in some center. And, certainly, people, let’s say, who are deletion 5q should actually have mutational analysis done because those who had p53 mutation may not necessarily have a good response to lenalidomide and may benefit from an earlier transplant evaluation. But, on the other hand, do we have enough data to suggest that people who have adverse mutational features actually are cured by transplant? And there were data from this conference that told you that the chances of relapse are higher in people who had transplant. Granted, it’s not a reason to say I’m not going to send my patient to transplant, but I think this whole science is evolving.

Vinod Pullarkat, MD: Yes. As we get more genomic data, there may be subsets of patients who may not benefit from transplant, and we should not subject them to transplant because it’s likely to be futile for those patients who have to go through all this morbidity. So, that is also a challenge. I think as transplant centers get more experience with genomic features that make a patient a poor candidate for transplant, that should be also incorporated. But, I think every patient who is a possible candidate deserves a consultation.

Ellen K. Ritchie, MD: I think so, too. Because if a patient suddenly worsens or takes a turn where you really believe that you need to transplant that patient within a reasonable period of time, unless you’ve done the homework where you’ve actually had them have the transplant consult, you’ve actually looked for a donor, you’ve actually identified a possible donor, it’s a very long period of time. So, the sooner that you actually determine whether or not a patient has a donor, whether or not you decide to go down that route or not I think is very important.

Transcript Edited for Clarity
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