What Is Mastocytosis?

So what is mastocytosis? Well, it's a neoplastic disorder with substantial increase in accumulation of clonal mast cells. And again, when it's only involving the skin, we call this cutaneous mastocytosis. We used to use other terms like urticaria pigmentosa, but for now, the current recommendation is using the term cutaneous mastocytosis for skin only.

When it's involving other extracutaneous organs, with or without skin involvement, we call it systemic mastocytosis. And of course, in rare situations, one can see a mast cell sarcoma. It's important to recognize that systemic mastocytosis is not the same as mast cell activation syndrome.

Mast cell activation syndrome is a hyperactivation disorder of clonal or non-clonal mast cells. And symptoms are due to mast cell activation, and they can be very similar, and that's why it can be very confusing to both patients and healthcare professionals to differentiate systemic mastocytosis and mast cell activation syndromes.

Classification of Systemic Mastocytosis

The classification of systemic mastocytosis. The World Health Organization, this edition contrasting it with the international consensus classification. And with non-advanced, this involves diagnoses of bone marrow mastocytosis, indolent systemic mastocytosis, or smoldering systemic mastocytosis, whereas the international consensus classification uses indolent systemic mastocytosis, which includes bone marrow mastocytosis and indolent systemic mastocytosis together and smoldering systemic mastocytosis.

However, the advanced form, patients are much more symptomatic. We refer to this as aggressive systemic mastocytosis. And then there's systemic mastocytosis with associated hematologic neoplasm and mast cell leukemia. And these are very similar, whether it's the World Health Organization or international consensus classification.

Systemic Mastocytosis: Epidemiology and Pathway to Diagnosis

So what is the epidemiology and pathway to diagnosis? Well, the prevalence for systemic mastocytosis is about one in 10,000 people, which translates to about 32,000 people in the United States.

It is considered an orphan disease in the United States as it affects less than 200,000 people. Diagnosis with systemic mastocytosis, we usually see the most common diagnosis as indolent systemic mastocytosis, affecting over 90% of patients, whereas systemic mastocytosis with a hematologic disorder is about 6%, which is very rare, and even more rare is mast cell leukemia, which is about 0.5%, extremely rare.

There's a mean of 6.5 years from symptom onset to diagnosis for patients with mast cell disease, largely because it presents as nonspecific symptoms and not readily recognized by clinicians as to what's going on.

Why Is Systemic Mastocytosis Presentation So Heterogeneous?

So why is systemic mastocytosis presentation so heterogeneous?

There's a lot of variability in mast cells and mast cell activation, masked with anatomic microenvironmental impact on mast cells. There's different surface receptors that direct mast cell response. These include CD2, CD25, CD30, and of course there's different mediator profiles.

There's an impact of high mast cell counts in a range of tissues and organs, which may be associated with organ damage, failure caused by mast cell infiltration, and this is particularly evident in advanced forms of systemic mastocytosis. There's also mutational heterogeneity. About 90% of patients with systemic mastocytosis carry a somatic point mutation of c-KIT, which is the D816V variant, but there's a number of other somatic mutations in other genes that have been associated with advanced systemic mastocytosis that could contribute to some of this variability.

KIT Mutations as Drivers of Systemic Mastocytosis

I mentioned that over 90% of patients have the KIT somatic point mutation, and this is a driver of systemic mastocytosis, and this receptor is activated by stem cell factor, and this is what leads to a series of responses that result in activation, proliferation, increased survival, and migration of mast cells to tissue.

Skin Lesions of Mastocytosis

Now, the skin lesions of mastocytosis, which is obviously something that gets most attention to clinicians because patients come in and say, I got all these freckles all over my body. What's going on here?

These are maculopapular lesions. They're monomorphic, but they can be present as part of indolent systemic mastocytosis or as isolated cutaneous mastocytosis, which may not be a systemic mastocytosis at all. Typically, they tend to be larger and more polymorphic lesions in children.

I would say about over 80% of patients with systemic mastocytosis have cutaneous involvement, but some adults do not have any skin involvement, and that can make it even more difficult to diagnose. In adults, it often starts on the thighs. It spreads to the trunk, distal extremities, and neck over time.

Systemic Mastocytosis Clinical Presentation

Looking at a nice overview of the clinical presentation of systemic mastocytosis and what is the involvement in terms of symptoms, and then also what mediators play a big role. For cutaneous, patients present with a lot of itching, blushing. They may have hives or swelling, histamine, tryptase is involved.

Other mediators are probably involved, related from mast cells, IL-6, latent activating factor, TNF, IL-8, IL-33, PGD2, and across the board, when you start having more systemic symptoms, patients may present with syncope or near syncope, dizziness, lightheadedness, heart racing. They may have gastrointestinal symptoms, get musculoskeletal pain, bone pain is common, aches and pain.

These patients often have osteopenia, osteoporosis, which is accelerated on bone scans and DEXA scans. They have oftentimes a lot of neurologic issues, which sometimes can let them be dismissed readily, thinking they just have anxiety and depression, but this is what's secondary to the underlying disease, and of course it can have respiratory as well as systemic symptoms as well. So all of these things, when you look at them, they're not very specific, a lot of non‑specific symptoms, so you have to have a high degree of suspicion, and you can see the overlapping effects of these different mediators that are released from mast cells that can be triggering many of these symptoms.

Common Triggers in Systemic Mastocytosis

The common triggers for mast cells can be extremes or changes in temperature, stress, fatigue, eating certain foods, drinking certain beverages, medications, infection, bee stings, you know, hymenoptera venom, when you see patients presenting with anaphylaxis, you really want to rule out underlying systemic mastocytosis as well as physical procedures, surgery and such. These can all be common triggers.

Diagnostic Algorithm for Mastocytosis

What is the diagnostic algorithm for mastocytosis?

Well, you have to have a high degree of suspicion, mast cell activation symptoms that we've talked about, or anaphylaxis, an elevated serum tryptase, you know, this is often seen, but it's a minor criteria, it's not always elevated, and so one has to have still have a high level of suspicion, adult onset mastocytosis in the skin, so if you see these lesions, and do biopsies, you can see positive increased numbers of mast cells, and this should potentially prompt for a more extensive evaluation. We can now get a serum KIT level to see if there is a mutation which correlates very well with bone marrow biopsy, but the definitive test would be bone marrow to show increased mast cells.

There's also mast cell immunophenotyping and looking for other mutations, such as the FIP1L1 and PDGFRA, this is especially important if there's eosinophilia present and the c-KIT is negative, as mast cells and eosinophils can coexist, and we have to look for other causes for these increased numbers of mast cells.

Diagnostic Criteria for Systemic Mastocytosis

The diagnostic criteria for systemic mastocytosis. The major criteria is multifocal dense aggregates in mast cells, which is 15 or more cells and aggregates in the bone marrow, or other extracutaneous organs.

This excludes the skin, as I mentioned, that's why we call it extracutaneous. Minor criteria is having 25% or more of mast cells with atypical morphology, and also have aberrant CD2, CD25, and also sometimes CD30 expression on mast cell. Having a positive KIT mutation, as we've discussed, or other activating KIT mutations in a baseline serum, tryptase of 20 or greater in the absence of a myeloid neoplasm.

So if you look at the World Health Organization criteria, you have to have one major and one minor, or three or more minor criteria, and this differs to the international consensus where you only need one major criterion for diagnosis, but three or more minor criteria for diagnosis. New and Emerging Therapies for Systemic Mastocytosis

Dr. Haumschild: Dr. Bernstein, thanks so much for that background. I think it's so helpful for us, right, to really resonate with the diagnostic criteria.

Considerations for Nonadvanced and Aggressive/Advanced SM

So what are some considerations for nonadvanced and aggressive or advanced systemic mastocytosis?

Well, we want to make sure that we're referring to specialized centers, as it's strongly recommended. While this diagnosis can be made by tryptase levels and bone marrow, I think it requires some specialty to identify it early on. We want to make sure there's a baseline DEXA scan to make sure that we're evaluating these patients.

And we're also counseling them regarding the signs and symptoms of disease. And then a really important piece is counseling patients to avoid known triggers of mast cell activation, such as, as Dr. Bernstein reviewed a little bit earlier, extreme temperature fluctuations, any type of stress, insect stings or venom. And then also, it's very important for these patients to carry injectable epinephrine, two auto injectors to really manage anaphylaxis because it's so highly associated with this disease.

And then lastly, we've got to continue to monitor the symptom burden and quality of life. And there are questionnaires that we can do that, so we can look at improvement over time when the patient has started their pharmacotherapy.

Treatment for Mast Cell Mediator–Related Symptoms

So what are some treatments for mast cell-mediated related symptoms?

We think about organ involvement. That's a great place to start.

Let's start with the skin. So we know that there's pruritus, flushing urticaria that can be commonly associated with this. And you want to have step-wise treatment. So H1, H2 blockers, leukotriene receptor antagonist, aspirins, ketotifen or cromolyn sodium are also opportunities for improvement and for treatment.

And then with the GI, we know that, you know, diarrhea, abdominal cramping, nausea, vomiting is going to be very uncomfortable for patients and impact their quality of life, their ability to come to work and perform those activities of daily living. So we want to focus in on H2 blockers, cromolyn, sodium, proton pump inhibitors, leukotriene antagonists.

And then neurologic, headache, poor concentration, brain fog. And again, you see H1 blockers, cromolyn, aspirin that come into play here.

And then cardiovascular, presyncope, tachycardia. Patients could have underlying comorbidities that we have to be aware of when we're analyzing these details. And I think that's where, again, treatment with H1, H2 blockers, corticosteroids can be introduced or omalizumab.

And then pulmonary, such as wheezing or throat swelling. We want to make sure, again, if it gets close to anaphylaxis, we have that epinephrine available. We can also use H1, H2 blockers, inhaled corticosteroids, bronchodilators.

And then the nasal ocular. So that stuffiness, pruritus. We will use intranasal H1, intranasal corticosteroids or cromolyn sodium.

Discussion: Conventional MC Mediator–Directed Therapies in Practice

What Would You Do for Sandy?

Dr. Bernstein: Well, you did a nice job outlining the treatment options, and really making a concerted effort to focus on the total patient and all the organ systems affected. And I think obviously the biggest trick here is to really have a high level of suspicion when patients present with these non-specific symptoms and don't dismiss them as anxiety or psychological issues. This is sometimes what we see a lot of and that's what delays the diagnosis.

But certainly H1, H2 blockers are mainstay treatment, and we tend to use the second-generation non-sedating antihistamines. And it's important that we dose them higher than what is the recommended dose. We tend to follow the guidelines for chronic urticaria if they have skin involvement, which is up to four times the recommended dose.

So that does make a difference using up to 20 mg, for instance, twice day of cetirizine or 360 mg twice day of hexapenidine. We use H2 blockers. We caution patients about leukotriene- modifying agents because of the box warning. Sometimes it can increase anxiety or vivid dreams and so forth. Some patients have had bad experiences or are prone to that. So, we might not necessarily jump on board with that right away.

If they have high levels of prostaglandin, F2-alpha in their at 24-hour urines, but we do try to get these diagnostic biomarkers, not just try to get 24-hour urines from methylhistamine, prostaglandin, F2-alpha, and leukotriene E4 as adjunct diagnostic test. We might put them on a baby aspirin or something to block prostanoids and so forth. So that's where we start.

Now we have a lot of GI issues, cromolyn sodium, we always like to document mast cells in different organ systems, and so it's that oftentimes these patients have had biopsies previously for other reasons, and we can usually get them stained for mast cells, and we can look at mast cell numbers and see if there's evidence that would suggest that cromolyn sodium would be helpful, and this can be dosed orally up to four times a day before meals. And we usually start with that, and then we kind of see where we are. We like to avoid oral steroids because, as you suggested, patients are prone to osteoporosis with high mast cell burden. They do produce a lot of mediators like heparin, which is osteoporotic, and so we try to avoid oral corticosteroids. And unfortunately, we don't have good topical treatments for skin lesions.

No matter, cromolyn sodium doesn't really work very well for topical cutaneous mastocytosis, but there are some novel therapies that are targeting mast cell, and we'll talk about that, could be useful in that context.

But so that's where we start. We try to see them back and see how they're doing. A lot of times these patients don't tolerate a lot of medicines too, so you have to be cognizant of that, and making sure that this is shared decision-making principles to make sure they understand what we're giving them and why we're giving it to them to make sure that it's tolerated.

Dr. Haumschild: Really well said, and Dr. Bernstein, a couple things that stood out to me in this discussion is, number one, getting to a specialist or someone that specializes in this is really important, right, to make sure that we're looking at the right KIT mutation, that we're making sure the patient's been worked up for an accurate differential diagnosis, and I think also making sure that patients know the right therapies because there's multiple systems impacted. And also, I think one of the main things that I think about, right, as a pharmacist that's evaluating a patient that's working in conjunction with you is, yes, I want to make sure these patients are on the right treatment, and I love how you said going for that second-generation antihistamine, right, because we don't want to cause drowsiness or impacts. But even with H1 blocker, cromolyn, these patients do need to be aware of anaphylaxis, and before anything comes up, to make sure that they have that epi on hand as well, in addition to taking the supportive care therapies for the different areas.

Dr. Bernstein: I agree with you, that's an important point is to have an epinephrine injector. This is not typical hives, isolated hives, where you don't need that. This is a systemic condition where syncope and anaphylaxis is certainly something that can occur and does occur in these patients.

Options Other Than Antimediator Therapies

Dr. Bernstein: We now are at a point where we have selective therapies to treat systemic mastocytosis, so these are new advancements in the treatment of an orphan disease. We really didn't have a lot to offer patients.

And so, there are patients who present with symptomatic indolent systemic mastocytosis or smoldering systemic mastocytosis. One can often either offer them a clinical trial if there's one available, or they can use avapritinib, which is approved now for indolent as well as aggressive systemic mastocytosis, and again, seeing individuals, whether they if they have a good response or don't tolerate it, then we can always try to do other things. There are other alternative therapies that have been used but are not specific for the diagnosis of these conditions. So I think it's very nice to know that we do have avapritinib, which is available for use. Before we were using other less specific tyrosine kinase inhibitors that may have had even more side effects.

Characteristics of KIT Inhibitors

Midostaurin, which is a multikinase inhibitor, has activity against both D816V, the mutant c-KIT inhibitor, but also the wild-type c-KIT inhibitor, and it is approved for treatment of advanced systemic mastocytosis as well as associated hematologic neoplasm forms of systemic mastocytosis and mast cell leukemia in adults. Imatinib, which has been around for a while, it's a KIT inhibitor approved for aggressive systemic mastocytosis in adults without the mutation, and then, of course, we mentioned avapritinib, which is much more highly selective. There's very negligible activity against the wild-type KIT, and it's now approved for advanced systemic mastocytosis, but also indolent systemic mastocytosis. It does cross the blood-brain barrier and has a higher potency versus midostaurin based on its inhibition of KIT816V.

Avapritinib vs Placebo in ISM: PIONEER Part 2

A study that compared avapritinib versus placebo in indolent systemic mastocytosis. It was called the PIONEER Study Part 2. It involved 212 patients with moderate to severe indolent systemic mastocytosis.

They had total symptom scores of 28 or greater, and they had uncontrolled symptoms despite two or more antimediator drugs, and so they were divided into a two-to-one randomization. Two times as many patients were given avapritinib, 25 mg once daily versus placebo as the best supportive care, which was the best supportive care, and this followed a 24-week treatment period with avapritinib or placebo, and then patients were also eligible to continue in an extension study to receive avapritinib for up to five years.

Avapritinib vs Placebo in ISM: PIONEER Part 2—Results

And what it showed was that avapritinib provided significantly greater improvement in symptom score and measures in mast cell burden compared to placebo.

Total symptom scores improved. Serum trip case scores reduced by 50% or more, and the KIT also decreased significantly, and the mast cell burden.

Long-term Improvements in QoL and Symptoms With Avapritinib in ISM: PIONEER

What about long-term improvements in quality of life and symptoms?

Avapritinib at both the 96-week and 144-week periods, total symptom scores were significantly reduced from baseline. If you look at individual domain symptom scores, both gastrointestinal, skin domain, as well as neurocognitive domain scores, they changed both at 96-week and 144-weeks compared to placebo, and the overall mastocytosis quality of life score, which is a validated score for looking at quality of life in these patients, also showed continuous improvement over the 96- and 144-week periods, respectively.

[00:45:07]

Avapritinib vs Best Available Therapy in Advanced SM

So when we look at data from both studies in advanced forms of systemic mastocytosis. The avapritinib group, which is including the Phase I EXPLORER and the Phase II PATHFINDER, again, this was looking at the best available therapy group with the retrospective chart review involved six sites, and it showed that patients who were on avapritinib versus best available therapy had better survival. The hazard ratios were 0.48, which was quite significant. They had longer duration of treatment, and they also had 60% greater reduction in serum tryptase levels.

All of these were statistically significant findings compared to best available therapies. Responses were significant also in patients who had received prior systemic therapy for their mast cell disease.

Avapritinib: Dosing and Administration

So how is it dosed? Well, it's for indolent systemic mastocytosis, it's given 25 mg once daily. For advanced systemic mastocytosis, it's given 200 mg once daily. It should be given on an empty stomach at least one hour before or two hours after a meal, and it's not recommended to repeat if vomiting occurs, and you do not want to make up for a missed dose within eight hours of the next dose. And there's significant prescribing information that's provided for patients when they are given this therapy.

Avapritinib: Safety—Warnings and Precautions, Common Adverse Reactions (No Contraindications)

There are safety issues that we certainly need to be aware of, that patients need to be aware of.

Intracranial hemorrhage was seen in about 2.9% of patients in both trials, and there was no events that were seen, however, in the indolent systemic mastocytosis trial, the PIONEER study, and fatal events was less than 1% of patients in all trials.

Cognitive effects, of course, one has evidence of that, it's recommended to withhold avapritinib depending on the severity, and photosensitivity is recommended to advise patients to avoid direct ultraviolet exposure. With respect to embryo fetal toxicity, it can cause fetal harm, so it's important to advise people of reproductive potential risk to the fetus and effective contraception.

So the most common adverse reaction to our clinical trial for advanced systemic mastocytosis was edema, diarrhea, nausea, fatigue, asthenia, and for indolent systemic mastocytosis, which was over 10% or more incidents, was eye edema, dizziness, peripheral edema and flushing.

Bezuclastinib and Elenestinib: Investigational Selective KIT Inhibitors

Now, there are other investigational selective KIT inhibitors, and one is elenestinib. The early data shows it does, improve symptoms, reduce tryptase, reduce the KIT mutation, decrease mast cell burden, and have favorable safety profiles.

Other Emerging Therapies

There are other emerging therapies. There's a masitinib, which is in Phase III trials, being looked at for severe indolent or smoldering systemic mastocytosis, but these data are forthcoming.

Discussion: KIT Inhibitor Therapy for Sandy Role of KIT Inhibitors in SM

Dr. Haumschild: Dr. Bernstein, as you're thinking about for a patient, innovative therapy like this that's more targeted, what are your thoughts as a clinician when you're looking to prescribe an agent for a patient that maybe continues to have symptoms beyond just the H1 blockers?

Dr. Bernstein: Well, I think that it certainly has made major advancements in terms of how we can manage patients. And we definitely discuss these selective KIT inhibitors with our patients. And because of the results of these studies that have been very encouraging and very effective, we certainly, I think patients when they read, you know, patients read inserts, they get worried about side effects and everything else.

And I think you have to frame it in a proper context and so forth. And generally, most of our patients are very receptive to starting this if they aren't doing a clinical trial. So those are the options, you know, we are very encouraged by what we're seeing in terms of its clinical effectiveness. And with that experience, we can also give patients some reassurance about safety and so forth.

Dr. Haumschild: Excellent. I would also agree, you know, it's a great opportunity to keep improving lives and providing hope, especially for those with this disease. And so, excited to see kind of how this area continues to evolve.

Unmasking the Patient Burden: Pharmacist-Focused Strategies to Improve Care

And now I'd like to transition us to unmasking the patient burden and really how pharmacists, can improve care.

Anaphylaxis Checklist for Pharmacists*

As we kind of transition into anaphylaxis, we know that there's got to be a checklist for pharmacists.

We've got to make sure that, you know, we dispense prescribed epinephrine devices, make sure they're prescribed, make sure that it's an appropriate dose and really have two on hand, as we talked about earlier, and remind patients, check your expiration date, make sure you have an action plan on hand and always carry your device, especially those with systemic masotitosis, as they are at increased risk of anaphylaxis.

So, we need to provide education, teach a patient, right, how to utilize the device, what's the correct storage, so we can maintain the potency, and then ensure patients have that as a first line for anaphylaxis, not antihistamines, right? So if they're having anaphylaxis symptoms, utilize that epinephrine, don't just take an H1 and hope it gets better. And then we know, too, as pharmacists, we're evolving to provide telepharmacy options for patients in rural areas, and we need to be prepared to educate and respond to anaphylaxis emergency training, making sure our staff are trained as well if a patient does emerge to the pharmacy.

Patient Anaphylaxis Education

As part of that patient anaphylaxis education, it's really coming up with an action plan. Patients should know that anaphylaxis is common in their disease. We educate them on the front end, report the prevalence to them, 24-49%, so this is something that patients may experience as part of their journey. And to make sure that patients, as we saw here, many with systemic mastocytosis had greater than one ED visits, 30%, or 14% actually use their epinephrine more than two times, which I think is significant.

So patients should know about this, we should educate proactively, make sure they have theirs on hand, and that way they're prepared if an event does occur.

Polypharmacy Is Common in Systemic Mastocytosis

We know that polypharmacy is also common in systemic mastocytosis. A lot of these patients are on different therapies, as we heard Dr. Bernstein talk about, bisphosphonates, antihistamines, antidepressants. And a lot of these patients are on greater than three prescription medications.

And so we need to be aware that pharmacists can do proper interprofessional communication, medication reconciliation, and to make sure that the healthcare provider knows exactly what that patient's on, and make sure we're doing our due diligence in our review.

Including Patients in Discussions About Medications Can Reduce the Risk of Polypharmacy

Include patients, patient-centered discussions, right? Shared decision-making of how patients can reduce polypharmacy, updating them on medications, making sure even if it's over-the-counter, we're including those as part of our assessment, and know that new treatments can change pretty significantly across the landscape. And we even saw in the PIONEER trial that patients using avapritinib were more likely to reduce or discontinue different treatments based on polypharmacy as best supportive care.

Multidisciplinary Care Is Often Needed for Systemic Mastocytosis

And then lastly, multidisciplinary care is needed.

Pharmacists can work to help make sure we're doing appropriate hand-offs. Guidelines recommend specialized centers, like we talked about earlier, so that we can make sure we're reviewing these patients and providing appropriate therapy.

Discussion: Communication Strategies for Pharmacists—Sharing Information and Decisions With Patients and HCPs on the SM Team

Key Takeaways

I'll give some of the big takeaways it's really important that pharmacists are partnering with specialists, making sure patients are getting the right referrals, we're doing medication reconciliation to reduce polypharmacy, and also educating patients. If we know a patient has systemic mastocytosis, to make sure that they have their anaphylaxis and epinephrine treatments, that they understand the medications they're taking, and build a good rapport, because it's a team-based approach to care that I think will set these patients up for success the most.

Q&A

Dr. Haumschild: Dr. Bernstein, what is your impression of the safety of the new systemic mastocytosis therapies, the KIT inhibitors, relative to more traditional therapies? Are they well tolerated?

Dr. Bernstein: Yeah, generally we found that they're well tolerated. They do have some mild side effects, some issues with some graying of the hair, pigmentation issues maybe that are mild, the skin, and also some transient neutropenia, but typically it resolves, and we find that both the approved avapritinib and the newer agents that are being investigated seem to be well-tolerated, and are very effective reducing mast cell burden.

Dr. Haumschild: What's been your experience with KIT inhibitors in practice, and have you seen that effectiveness that we saw for clinical trials in the lives of your patients?

Dr. Bernstein: Yeah, we have, and patients notice improvement, and they're generally well-tolerated in terms of, and some people might say they had some initial mild nausea, but it resolved, and they did very, they've done very well taking this medicine on an ongoing basis and has made a difference in their overall quality of life and clinical improvement.

Dr. Haumschild: Nasal epinephrine is now also available, sometimes might be similar to use. Do you recommend injectable or nasal, or do you see them both as being options for these patients?

Dr. Bernstein: The data looks like it's effective in terms of, you know, having the necessary impact within that immediate, from a pharmacokinetic perspective, similar to subcutaneous, slightly slower, but overall still very effective, and which led to its approval by the FDA. So I think that's going to be patient preference, and also maybe affordability, perhaps coupons and things of nature. Hopefully, pharmacists will help advise patients as they come in, but that's going to be patient preference, and we'll see how it unfolds, because it just was recently approved, not too long ago, several months.

Dr. Haumschild: Well, I appreciate you Dr. Bernstein, thank you so much.

Remember our key takeaways. Refer patients for further assessment if systemic mastocytosis is suspected, preferably to a center of care. Treatment options include antimediators, and cytoreductive therapies, and remember KIT mutations, especially KIT D816V, are drivers of the pathophysiology, and these selective KIT inhibitors are important emerging treatment options we should be aware of.

And lastly, people with SM commonly receive many treatments, and need treatment adjustments, communication between their care provider and pharmacist, and that's critical for optimal care and success.