Newer Agents and Precautions to Avoid Complications of Sickle Cell Disease

Peter Salgo, MD: To me it seems as if all these drugs buy you time while we’re working on the fundamental issue of a cure. Am I oversimplifying?

Sophie Lanzkron, MD, MHS: Well, so we’re probably a long way from every person born with sickle cell disease in this country getting curative therapy. We have a long way to go before we’re at that point. And so, having all these other therapies I think are appropriate. I mean when are we going to get to the point where we’re going to transplant folks with sickle cell disease, but we still need therapies because there’s a lot of morbidity and suffering there. So, I think there’s lots of room for the advancement and additional therapeutics coming out beyond just thinking about and focusing on gene therapy.

Elliot Vichinsky, MD: And as was pointed out, there is a morbidity that families make a decision about with these therapies, with myeloablative right now, you know? They have the same risk of other myeloablative busulfan things, you know, veno-occlusive disease, thrombosis, hospitalization, platelets, and then the issue of sterility. Patients want to make their own decisions, as you would with a chronic illness.

Do you take these daily meds and not take the risk of a potential death, even though you have improved? There are family decisions that are individualized.

Peter Salgo, MD: And it’s not unique to this disease. There have been, let’s go back 10 years. There’s a classic New England Journal of Medicine article on CABG [coronary artery bypass graft] surgery versus medical therapy, versus stint. With a CABG operation you take all that risk and frontload it. All these others you’re sort of incrementalizing the risk as you go out. Same decision though, isn’t it? No?

Jane Hankins, MD, MS: I always think it’s so individualized. I agree with Elliot. It depends on your values. I’ve done research on risk taking. There are people who are greater risk takers, there are people who are lesser risk takers. It’s so individual.

Sophie Lanzkron, MD, MHS: I think it’s the classic question about sickle cell disease, right? When we think about how patients get treated in the emergency department, we’re really all moving toward patient-specific treatment plans. These discussions seem to be individualized per person, and their families.

Peter Salgo, MD: Based on my clinical experience, I can tell you the wrong way to treat them is periodically in the emergency department.

Sophie Lanzkron, MD, MHS: Oh absolutely, yeah.

Peter Salgo, MD: Get something and go home. That’s just wrong. And anything you can move away from that and toward these new therapies sounds to me better.

Jane Hankins, MD, MS: I’ve always thought the emergency department was the worst place for patients with sickle cell disease.

Peter Salgo, MD: And it’s not the fault of the emergency department either.

Jane Hankins, MD, MS: No, it isn’t.

Peter Salgo, MD: What other agents are there out there in the pipeline, other than what we’ve discussed that are looking interesting?

Biree Andemariam, MD: Well I think it’s like we could talk about like targets. There are multiple drugs for multiple targets. I think about those that modify the cyclic GMP pathway, and there are at least 3 I can think of, all oral.

Peter Salgo, MD: Oral?

Biree Andemariam, MD: All oral medications, all I believe in phase 2 development. Early results are showing increases in fetal hemoglobin, possible increases in total hemoglobin, decreases in solu P-selectin. But these are early. As well as maybe some indication in markers of improvement in organ damage. So that’s 1 class.

Peter Salgo, MD: Okay. There’s a class of drug we haven’t mentioned, because we’ve all been talking about iron overload. Does chelation therapy play any role here?

Jane Hankins, MD, MS: Yes.

Biree Andemariam, MD: Yes.

Elliot Vichinsky, MD: I do think there are other drugs going on: oral decitabine, THU. There’s actually a very dramatic number of phase 1, phase 2 trials that are going on in sickle cell now that we could put out. But I do think there will be other advantages to new drugs that can add to the armamentarium of how to treat trickle cell, they’re exciting.

And I do support what you’re talking about, iron overload, because no matter how you want to cut it, true sickle cell patients are recurrently transfused for many reasons. Many of appropriate reasons and some inappropriate reasons. And so iron overload is a common problem in sickle cell disease.

Jane Hankins, MD, MS: And we know that having overload makes the phenotype worse.

Peter Salgo, MD: Let’s take a look a now and ask, in terms of non-high-tech therapy, just generic general recommendations patients can follow on their own to avoid some of the complications of sickle cell disease. These go back in time a long way, right?

Jane Hankins, MD, MS: I would say, number 1, find a person who knows a good therapist. Find a primary care provider who specializes in sickle cell disease. You have to have that contact. It’s OK if you see others. Even if you see that person once a year, but you have to find that person.

Peter Salgo, MD: OK. What about, I suspect, let me be deliberately humorous here, they really shouldn’t climb Mt Everest.

Sophie Lanzkron, MD, MHS: True.

Biree Andemariam, MD: True.

Jane Hankins, MD, MS: Probably.

Elliot Vichinsky, MD: There’s an alternative to that argument that I just want to bring up because I’ve noticed, and I think it’s true, is that one of the problems patients with sickle cell disease have when they get older is, they haven’t developed necessarily healthy lifestyles with exercise, eating, and things.

So actually, there are a fair amount of data developing now that for these diseases, that we need to focus on general health and exercise. I don’t want to present the position that they can’t exercise or eat well. There are so many people talking about the exposure of cold water or high altitude. The population as a whole hasn’t been vigorously encouraged to meet the basic guidelines. So, I do think they don’t want to go mountain climbing, but I also think they need to do health-motivated care, which will help.

Peter Salgo, MD: I’ll play devil’s advocate again. You’re going to exercise vigorously. Your end organs are going to get relatively hypoxic. You know, feel the burn.

Sophie Lanzkron, MD, MHS: We don’t tell patients to feel the burn, right? Right. So, there are limitations and thoughtful exercise. But I also want to emphasize the idea that we tell patients to stay hydrated and all. And we tell them those things, a lot of data, but when patients come in and say, “Oh, well, I didn’t drink enough. I don’t think I drank enough,” and they blame themselves for developing a vaso-occlusive crisis. That can happen even when you’re doing all the right things.

Jane Hankins, MD, MS: Exactly, exactly.

Sophie Lanzkron, MD, MHS: And we want to make sure patients don’t feel like they’re blaming themselves for the development of their complications.

Peter Salgo, MD: The old blame the patient thing. You know, doctors do this. It seems to me that’s less likely to explain most of this.

Biree Andemariam, MD: Yeah. But the other thing that I would tell patients is to be an active participant in their care. Be your own advocate if you feel like you can’t find someone close to you who can do that for you. Because I think that that’s helpful. Not everyone is going to find an expert. But if you can maintain proper knowledge about your disease and educate yourself on treatments that we’ve discussed today, that there’s a lot that the individual patient can do to improve the course of their own lives.

Sophie Lanzkron, MD, MHS: And the American Society of Hematology isn’t going to take the guidelines and make them into patient friendly tools so that patients can become more aware of what they need to have done.

Transcript edited for clarity.