Table 5.
Precision medicine-based therapy in patients with systemic mastocytosis (SM).
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| Condition/indication | Recommended therapy |
| --------------------------------------------------------------------------------------------------------------- | |
| Anaphylaxis/hypotension | 1. HR1+HR2 blocker (basic therapy) 2. Glucocorticosteroids 3. Specific immunotherapy (known bee or wasp allergy) 4. Omalizumab (IgE-dependent allergy) |
| Confirmed involvement of | Aspirin * + HR2 blocker |
| arachidonic acid derivatives (PGD2) | |
| Severe anaphylaxis/MCAS | Omalizumab |
| GI-tract problems | |
| Ulcerative GI tract disease | 1. Appropriate doses of HR2 blocker |
| Resistant ulcerative GI tract disease | 2. Proton pump inhibitors + HR2 blocker |
| Crampi, constipation, loose stools | HR2 blocker |
| Chronic diarrhea | Appropriate doses of HR2 blocker |
| With dense mast cell infiltrates | Consider cytoreductive therapy (when C-Findings are recorded) |
| With ascites and hepatopathy | Consider cytoreductive therapy (C-Finding fulfilled) |
| Osteopenia/Osteoporosis | |
| Progressing osteopenia | Bisphosphonates when T-score < −2 |
| Osteopathy with vitamin D deficiency | plus Vitamin D (+/− vitamin K2 **) |
| Osteoporosis (T Score < −2) | Bisphosphonates |
| Resistant osteoporosis | plus RANKL inhibitor and/or plus low dose interferon-alpha |
| Skin involvement in SM | HR1 blocker |
| Severe/resistant skin symptoms | plus glucocorticosteroids (systemic/topical) and/or UVA or PUVA therapy |
| Disease progression without AHN | |
| KIT D816V+ ASM with slow progression * | Cladribine, midostaurin, IFN-A |
| KIT D816V− ASM with slow progression * | Imatinib, masitinib, midostaurin |
| ASM with rapid progression or MCL | Polychemotherapy + HSCT |
| ASM or MCL not eligible for HSCT | |
| or not willing to have a HSCT | Cladribine, midostaurine, IFN-A |
| Palliative management | HU, midostaurin, BSC |
| Disease progression with/to AHN | |
| ASM-AHN or MCL-AHN | Separate treatment plans: |
| or ISM-AHN | treat the AHN portion of the disease as if no SM was diagnosed and SM portion as if no AHN was found |
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* Aspirin is not recommended for patients with GI tract disease or a high risk of development of an ulcerative GI disease. In addition, aspirin may provoke idiosyncratic reactions and severe hypotension. Note also that relatively high doses of aspirin (500 mg/day or more) are required to suppress prostaglandin synthesis in mast cells in patients with mastocytosis. ** In young and fit patients who are eligible, HSCT must be considered, independent of the response to initial therapy. In those who respond well to interventional therapy, no HSCT may be required or may be delayed. Abbreviations: HR, histamine receptor; IgE, immunoglobulin E; MCAS, mast cell activation syndrome; PGD2, prostaglandin D2; MCAS, mast cell activation syndrome; GI tract, gastrointestinal tract; UVA, ultraviolet light; AHN, associated hematologic (non-mast cell) neoplasm; ASM, aggressive systemic mastocytosis; MCL, mast cell leukemia; IFN-A, interferon-alpha; HSCT, hematopoietic stem cell transplantation; HU, hydroxyurea; BSC, best supportive care.