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Advanced systemic mastocytosis is the dangerous form of this rare blood cancer, in which KIT-mutant mast cells damage the marrow, liver, gut or bones, grow alongside a second blood cancer such as chronic myelomonocytic leukaemia, or flood the blood as mast cell leukaemia. The KIT-blocking tablets midostaurin and avapritinib have replaced older chemotherapy, and fit patients may have a transplant.
Advanced systemic mastocytosis comprises three WHO entities united by KIT D816V-driven mast cell proliferation with organ damage or an accompanying neoplasm. Aggressive systemic mastocytosis is defined by C findings: cytopenias from marrow infiltration, liver dysfunction with ascites, hypoalbuminaemia and weight loss from gut involvement, or large lytic bone lesions. Systemic mastocytosis with an associated haematological neoplasm (SM-AHN), the commonest advanced form, pairs mastocytosis with a myeloid neoplasm, usually chronic myelomonocytic leukaemia, a myelodysplastic or myeloproliferative neoplasm or acute myeloid leukaemia, which arises from the same KIT-mutant or an earlier clone and often carries SRSF2, ASXL1 or RUNX1 mutations that predict shorter survival on the MARS and IPSM scores. Mast cell leukaemia, with 20 percent or more mast cells in the marrow aspirate, is the rarest and most lethal form. Serum tryptase is usually very high and KIT D816V allele burden in blood reflects the whole disease.
Before 2017 treatment was cladribine, interferon alfa or hydroxycarbamide, with responses in a minority. Midostaurin, a multikinase inhibitor active against KIT D816V, produced responses in 60 percent of 116 patients with advanced disease in a phase 2 trial (New England Journal of Medicine 2016) and was approved in 2017; avapritinib, a selective KIT D816V inhibitor, produced responses in three quarters of patients in the EXPLORER and PATHFINDER trials with deep falls in tryptase and allele burden and was approved in June 2021 for advanced disease, restricted to patients with platelets of 50 x 10^9/L or more because of intracranial haemorrhage at higher doses in thrombocytopenic patients. Avapritinib is now the preferred first-line agent in the NCCN guideline, midostaurin the alternative, and bezuclastinib is in the Apex trial as a further selective inhibitor. The associated neoplasm is treated on its own merits, for example with azacitidine for chronic myelomonocytic leukaemia or intensive chemotherapy for acute myeloid leukaemia, and allogeneic transplantation is the only curative option, considered for mast cell leukaemia, aggressive disease responding to a KIT inhibitor and SM-AHN with a high-risk neoplasm. Supportive care for mediator symptoms, bone disease and anaphylaxis continues throughout.
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
Leukaemias, myeloma and MDS live in the marrow and blood; lymphomas grow in lymph nodes and spleen. The node stations are the disease map, not a route of spread, and staging counts them.
In lymphoma the node stations are the disease itself; staging (Ann Arbor / Lugano) counts how many regions and sides of the diaphragm are involved.
Same organ: High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma), Mediastinal grey zone lymphoma, Primary effusion lymphoma, Plasmablastic lymphoma, T-cell/histiocyte-rich large B-cell lymphoma, EBV-positive diffuse large B-cell lymphoma, Primary large B-cell lymphoma of the testis, Gastric MALT lymphoma, Ocular adnexal MALT lymphoma, Extranodal NK/T-cell lymphoma, Adult T-cell leukaemia/lymphoma, ALK-positive anaplastic large cell lymphoma, ALK-negative anaplastic large cell lymphoma, Breast implant-associated anaplastic large cell lymphoma, Primary cutaneous anaplastic large cell lymphoma, Lymphomatoid papulosis, Mycosis fungoides, Enteropathy-associated T-cell lymphoma, Monomorphic epitheliotropic intestinal T-cell lymphoma, Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), Splenic marginal zone lymphoma, Nodal marginal zone lymphoma, Primary cutaneous marginal zone lymphoma, Primary cutaneous follicle centre lymphoma, Sezary syndrome, Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma), Hepatosplenic T-cell lymphoma, Intravascular large B-cell lymphoma, Lymphomatoid granulomatosis, T-cell prolymphocytic leukaemia, Splenic B-cell lymphoma/leukaemia with prominent nucleoli (formerly B-cell prolymphocytic leukaemia and hairy cell leukaemia variant), T-cell large granular lymphocytic leukaemia, Mixed-phenotype acute leukaemia, Myeloid leukaemia of Down syndrome, Burkitt leukaemia, Marginal zone lymphoma, Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome), Primary mediastinal (thymic) large B-cell lymphoma, Leukaemia (all types), Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Chronic lymphocytic leukaemia, Chronic myeloid leukaemia (CML), Diffuse large B-cell lymphoma, Follicular lymphoma, Hodgkin lymphoma, Mantle cell lymphoma, Multiple myeloma, Non-Hodgkin lymphoma (all types), Myelodysplastic syndromes / neoplasms (MDS), Myeloproliferative neoplasms (PV, ET, myelofibrosis), Polycythaemia vera (PV), Essential thrombocythaemia (ET), Waldenström macroglobulinaemia, Hairy cell leukaemia, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Burkitt lymphoma, HIV-associated (AIDS-related) lymphomas, Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Systemic mastocytosis, Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, Langerhans cell histiocytosis (LCH), Post-transplant lymphoproliferative disorder (PTLD), FLT3-mutated acute myeloid leukaemia, IDH1- and IDH2-mutated acute myeloid leukaemia, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Secondary and therapy-related acute myeloid leukaemia, Acute promyelocytic leukaemia, Acute myeloid leukaemia in older or unfit patients, Smouldering multiple myeloma, Newly diagnosed multiple myeloma, transplant-eligible, Newly diagnosed multiple myeloma, transplant-ineligible, Relapsed or refractory multiple myeloma, Plasma cell leukaemia, Lower-risk myelodysplastic syndromes, Higher-risk myelodysplastic syndromes, Chronic lymphocytic leukaemia, first treatment, Relapsed or refractory chronic lymphocytic leukaemia, Richter transformation of chronic lymphocytic leukaemia, Chronic myeloid leukaemia, chronic phase, Chronic myeloid leukaemia, accelerated and blast phase, Primary myelofibrosis, Standard-risk B-cell acute lymphoblastic leukaemia in children, High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL), Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL), Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL), Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year), Relapsed and refractory acute lymphoblastic leukaemia in children, Acute myeloid leukaemia in children, Erdheim-Chester disease, Rosai-Dorfman-Destombes disease, Single-system Langerhans cell histiocytosis (bone, skin or one other organ), Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement), Indolent and smouldering systemic mastocytosis, Early-stage classical Hodgkin lymphoma (stage I to II), Advanced-stage classical Hodgkin lymphoma (stage III to IV), Nodular lymphocyte-predominant Hodgkin lymphoma (nodular lymphocyte-predominant B-cell lymphoma), Relapsed and refractory classical Hodgkin lymphoma
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Also on OnCo: Symptoms and red flags · Early detection roadmap.
Bone marrow biopsy and aspirate, KIT D816V allele burden, myeloid mutation panel, tryptase, imaging for organomegaly and bone lesions, MARS or IPSM score.
Avapritinib 200 mg daily when platelets are 50 x 10^9/L or more (EXPLORER, PATHFINDER, approved 2021); midostaurin as the alternative (approved 2017).
Treat the neoplasm on its own merits (azacitidine for CMML or MDS, intensive chemotherapy for AML) alongside or after KIT inhibition.
Switch between avapritinib and midostaurin; cladribine; interferon alfa; bezuclastinib in the Apex trial.
Allogeneic haematopoietic cell transplantation after response to a KIT inhibitor.
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The names and definitions on a marrow report (for example MDS with biallelic TP53 inactivation, or AML myelodysplasia-related) come from this document or from the parallel International Consensus Classification.
Avapritinib is the most active drug in advanced systemic mastocytosis; platelet counts must be checked before and during treatment.
Avapritinib is the preferred first targeted therapy for advanced systemic mastocytosis in patients with adequate platelet counts.
Midostaurin was the first effective targeted therapy for advanced systemic mastocytosis and remains an option, particularly where avapritinib is unsuitable or unavailable.
Query for this cancer: (TITLE:"Advanced systemic mastocytosis" OR ABSTRACT:"Advanced systemic mastocytosis" OR TITLE:"aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia" OR ABSTRACT:"aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia" OR TITLE:"AdvSM" OR ABSTRACT:"AdvSM" OR TITLE:"Aggressive systemic mastocytosis" OR ABSTRACT:"Aggressive systemic mastocytosis" OR TITLE:"ASM" OR ABSTRACT:"ASM" OR TITLE:"SM-AHN" OR ABSTRACT:"SM-AHN") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia), not a curated reading list.
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Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
Take with food; antiemetic prophylaxis.
Possible QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
Several lymphoma treatments knock out the part of the immune system that keeps a particular lung infection, Pneumocystis, at bay. A low-dose antibiotic three times a week prevents it, and a separate tablet prevents shingles.
See all on the product pages:AvapritinibAzacitidineCladribineMidostaurin·Printable cards in the navigator
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