Crizanlizumab Use in Sickle Cell Disease


Panelists share their perspectives on the selection and use of crizanlizumab in certain patients with sickle cell disease.


Ifeyinwa Osunkwo, MD: Excellent. Dr Desai, I’m going to move on to the next medication, crizanlizumab, which was approved in 2019 for sickle cell disease. Can you talk to us a bit about indications, risk/benefit ratio, adverse effect profile, etc?

Payal Desai, MD: I’ll start where Dr Shah finished, which is that it was in addition to hydroxyurea. The first dose is an IV [intravenous] infusion, it’s the only one on the list in terms of FDA-approved medications that is an IV infusion. For the first month, you get 2 doses, and then it’s once a month. In terms of how it works, it is a P-selectin inhibitor, so it helps bind up the selectins that are on platelets and things that help with adhesion to the blood vessel wall. When you block these adhesions, you block not just the platelets, but you also impact the white cells, the red cells, all of that whole process is impacted by inhibiting these selectins. The data that got crizanlizumab approved, on the higher dose of the medication, which was the FDA-approved medication for the adult population, you get a 45% reduction in painful episodes. There was a longer time to that first vaso-occlusive episode and longer time to that second vaso-occlusive episode. Again, all of those were the reasons it got approved.

In my mind, all of the medications beyond the hydroxyurea are second line, meaning we don’t have as much information, we don’t know the role on cardiovascular disease and kidney disease, we just don’t have enough information on how they are impacted. My hope is that there will be a positive impact when you’re affecting vaso-occlusive episodes as we were talking about, but we need more time and data to know how they impact long-term complications. Again, I use it in conjunction with hydroxyurea. For the patients who can’t tolerate hydroxyurea for whatever reason, whether that’s GI [gastrointestinal] upset, headaches, their blood counts, all of those reasons, I use crizanlizumab by itself as well. I will tell you that some of my patients like the idea of a once a month IV infusion; they don’t want to take a pill every day, they would prefer to have an IV infusion. That’s what we’ve heard from patients.

In terms of adverse effects, the main thing is infusion reactions, and it’s variable degrees. Some people can have a very mild reaction, and some people can have a much more moderate to severe reaction. The mild reactions are usually a bit of itching afterward, and patients may say that the day they got their infusion, they might have felt a bit more icky. I would love to hear what other people do too, but I premedicate with Benadryl [diphenhydramine] and Tylenol [acetaminophen] before I do the infusion. There are no guidelines, so this is what my clinical practice is. We found that, again, we had fewer of those minor complications.

In terms of more severe reactions, I have seen a few, and they are scary. They can be a severe vaso-occlusive episode, they can be fever, they can be a bump in LFTs [liver function test levels]. We’re still trying to understand what that means, and how to prevent that, because we’re premedicating all of our patients. We’re still seeing, at least I’ve seen a couple in the past year and a half that, it’s been enough that I get worried about the patient. All of them have done OK afterward, but they required hospitalization for a severe vaso-occlusive crisis. Their LDHs [lactate dehydrogenase levels] were the highest I’ve seen. Again, those are real, and they’re scary, and they require some supportive care. People will get fevers during that. I’ve had people then start to look for acute chest syndrome, and you should. But most of the time, it’s been the infusion reaction, and that huge cytokine response to that infusion that happens.

Ifeyinwa Osunkwo, MD: That is interesting. I haven’t seen it that severe, but I have seen the significant pain episode. We haven’t made it a universal practice to premedicate. However, what I’ve seen a lot and I don’t know if it’s just living in warmer weather, is flank pain, especially if we know that they’re dehydrated by their history. They come in, they just rolled out of bed and showed up in the clinic, haven’t had anything to drink. Oh, my goodness, the flank pain is unreal. Now we prehydrate most of them before they get their medicine, but we haven’t moved on to Benadryl and Tylenol yet. I’d love to hear what Nirmish and Wally see with crizanlizumab. Then we’re going to move to the next exciting section, which is talking about curative therapies for sickle cell disease.

Nirmish Ramesh Shah, MD: I can get started. The emphasis here is that we’re still learning how to best leverage these new medications. For crizanlizumab, I explain to patients that this is a monoclonal antibody, a really smart person in the laboratory figured out how to make this, but it’s humanized, and it’s not you. So when we infuse this medication, your body’s kind of saying, “Well, this ain’t me,” and then has a reaction to it. My job is, how do I help you through that? For the most part, most patients seem to get better with subsequent infusions.

Now, I do put a big emphasis on hydration, and patients do just roll out of bed and come in and they don’t have breakfast, they don’t do anything. I ask them, actually encourage them, to come in with their Chick-fil-A, or McDonald’s, or whatever. Just pick up something, bring it in, eat it while I’m waiting with the IV team and getting the drug to the bed. That seems to have helped, and then I have a really low threshold of premedicating, however it’s not universal. I have a low threshold, and even for the beginning, I have no problem slowing the infusions. Even if I have to cut it off early, if they’re starting to get achy, we’ll get you the full dose next time. You’re right, if you start to have that reaction, and it’s because of the monoclonal antibody that your body’s reacting, I just want to ease that patient into it. That seems to have worked, but as I said, we’re all learning, and I think that we’ll get better at how to make sure that we have fewer of those adverse effects. However, it is true that we need to make sure we watch patients closely.

Transcript edited for clarity.

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