Back Back
Managing Systemic Mastocytosis Expert Answers
Managing Systemic Mastocytosis: Expert Guidance on Symptom Identification, Vaccination, and Treatment Strategies

Released: March 20, 2025

Expiration: March 19, 2026

Matthew Giannetti
Matthew Giannetti, MD
Activity Information

Activity

Progress
1
Course Completed
Continue
Key Takeaways
  • All healthcare professionals who suspect systemic mastocytosis (SM) in patients presenting with symptoms should use peripheral blood testing, biopsies, and PCR-based testing to evaluate serum tryptase levels and KIT mutation(s).
  • In general, SM is not an inheritable disease, and patients should be vaccinated per CDC guidelines, given they are monitored as needed.
  • Avapritinib has been approved by the FDA to treat patients with indolent or advanced SM, though it should be discussed with patients that they are likely to be on this agent indefinitely.

This commentary dives more deeply into topics and questions posed by a live audience of healthcare professionals (HCPs) during a webinar on the current advancements in managing systemic mastocytosis (SM), including strategies for diagnosing SM in those presenting without rash and with other symptoms, administering vaccinations, and using avapritinib to treat indolent or severe disease. This webinar was held in January 2025.

Are dense, multifocal aggregates confirmed via biopsy? If so, should primary care providers look for increased tryptase levels and KIT mutations if patients present without rash but with other typical symptoms of SM? 
The formal diagnostic criteria for SM require a biopsy. So, the dense, multifocal aggregates mean that HCPs need to look in the bone marrow or GI tract. Primary care or allergy HCPs should look almost exclusively at skin findings during examinations. If patients do not have a rash, HCPs should also look at serum tryptase levels. My advice: be very careful with tryptase because approximately 6% of the general population has elevated levels at baseline. HCPs also should look for KIT mutations using a PCR-based test. For example, most HCPs are going to use less invasive options like peripheral blood testing for initial workup.

Can patients pass SM to their offspring?
In general, SM is not an inheritable disease. I tell my patients that SM is an acquired, somatic mutation, not a germline mutation. Parents cannot pass SM to their kids and, more importantly, patients did not get it from their parents. Furthermore, SM does not seem to negatively affect fertility, nor does it appear to lead to severe or life-threatening complications. That said, there are several reports of germline KIT mutations that are familial disorders. These are exceptionally rare and often present at birth.

What percentage of patients do you refer to oncology?
I prefer to manage all patients myself. I manage most patients with aggressive disease in conjunction with oncology. It is useful to comanage with an oncologist when patients develop cytopenias or progressive organ failure. I refer to oncology for cytoreductive therapy and bone marrow transplant.

For patients with indolent SM, I think they are best managed by an immunologist. This is the mast cell, so (as clinical immunologists) we own this cell. It causes food allergy, allergic rhinitis, and hives; therefore, it is our little area of the immune system. I think patients with SM do better if they have an HCP who knows about mast cells managing them.

Should patients with SM receive vaccinations or is there a risk for anaphylaxis?
Patients should be vaccinated based on CDC recommendations. Per current data, these patients can even safely receive the COVID-19 vaccine. The caveat here is that patients with mastocytosis have a higher rate of adverse reactions—almost exclusively hives or flaring of their cutaneous lesions. Following the increased development of mRNA-based vaccines, we now have data on the 2 mRNA COVID-19 vaccines, showing that both appear to be safe to use in patients with SM. The respiratory syncytial virus also has an mRNA-based vaccine available for patients aged 60 years and older, but it has not been studied in patients with SM. Regardless, in my opinion, the benefit of a vaccination (ie, not acquiring said disease) outweighs the risks associated with vaccination.

It is also important to note that patients can flare up quite considerably with viral infections. At least once a year, I see a patient with mononucleosis or severe influenza and relentless hives that occasionally provoke anaphylaxis as well. So, there are consequences with viral infections, not just with vaccines.

Is there any role for doxylamine succinate or cetirizine for patients with SM?
HCPs can use these agents but note that second-generation antihistamines are better. First-generation antihistamines like doxylamine, diphenhydramine, and cyproheptidine are lipophilic compounds that cross the blood–brain barrier. There is some pretty convincing evidence that their cumulative use leads to increased risk for early-onset dementia. Because of this, I push people away from first-generation antihistamines in all aspects of care. In particular, patients with SM are going to be on antihistamines for most of their life. So, if they are young, it is preferable to use a second-generation antihistamine. Although doxylamine succinate is fine to use as needed, it should not be used for chronic, nightly use.

Are there any GI disorders/diseases associated with SM?
There are GI symptoms associated with SM but not necessarily specific GI disorders or diseases. Mast cells are all over the GI tract, and HCPs can occasionally pick them up in aggregate via biopsy—which is what is causing GI symptoms—in patients with SM.

Further, although there are no disease associations with SM, there are certain associations with KIT mutations. D816V is the dominant KIT mutation in SM, yet some non-D816V KIT mutations can cause GI stromal tumors, piebaldism, and may be observed in multimutated acute myeloid leukemia.

How long, if not indefinitely, do you use avapritinib to treat patients with advanced or indolent SM?
This is a good question. I tell my patients that they will most likely be on this agent indefinitely. Avapritinib at daily doses of 25 to 50 mg does not appear to clear all KIT-mutation bearing mast cells from the bone marrow. As such, patients experience recurrent symptoms if they discontinue avapritinib for a prolonged period, such as in preparation for or recovery from surgery.

The goal that we are trying to reach in SM is something akin to current management practices for chronic myeloid leukemia, where HCPs administer high doses of targeted therapies and/or chemotherapy to achieve treatment-free remission. Then follow-up via peripheral blood in a noninvasive manner is done to monitor for recurrence. In SM, we do not have a single diagnostic test; we must use a combination of tests or array of targeted therapies. Avapritinib is a promising option, but it is probably going to require a longer treatment duration. If you ask me again in 5 years, the answer to this question will likely change, but avapritinib is currently considered a long-term therapy. However, more long-term data are required to confirm this.

Your Thoughts
How often are you prescribing avapritinib for your patients with advanced or indolent SM? You can get involved in the conversation by answering the poll question and posting a comment below.

Continue

Poll

1.

How often are you prescribing avapritinib for your patients with advanced or indolent SM?

Submit