scholarly journals Efficacy of Omalizumab in Indolent Systemic Mastocytosis

2019 ◽  
Vol 2019 ◽  
pp. 1-5
Author(s):  
Calum Slapnicar ◽  
Martina Trinkaus ◽  
Lisa Hicks ◽  
Peter Vadas
Keyword(s):  
Mast Cells ◽  
Allergic Asthma ◽  
Retrospective Analysis ◽  
Chronic Urticaria ◽  
Systemic Mastocytosis ◽  
Heterogeneous Group ◽  
Internal Organs ◽  
Indolent Systemic Mastocytosis

Background. Systemic mastocytosis (SM) comprises a heterogeneous group of disorders characterized by the proliferation of clonal mast cells in skin and various internal organs. Omalizumab is an established, labelled therapy for allergic asthma and chronic urticaria, but its experience in the efficacy of SM is limited. Methods. A retrospective analysis of 6 patients diagnosed with indolent SM treated with omalizumab at St. Michael’s Hospital between 2009 and 2018 is described. Reported frequency of anaphylaxis, baseline and follow-up tryptase levels, and SM-related symptoms were captured to measure the control of the disease. Results. Of the 5 patients who had experienced unprovoked anaphylaxis prior to treatment with omalizumab, 3 had no further episodes of anaphylaxis following initiation of omalizumab, while the remaining 2 patients had milder multisystem reactions. Significant improvement in cutaneous symptoms was also observed. Conclusion. These data suggest that omalizumab provides benefit to patients with SM who remain highly symptomatic in spite of treatment with conventional therapies.

scholarly journals IgE-Related Chronic Diseases and Anti-IgE-Based Treatments

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Arnau Navinés-Ferrer ◽  
Eva Serrano-Candelas ◽  
Gustavo-J Molina-Molina ◽  
Margarita Martín
Keyword(s):  
Allergic Asthma ◽  
Chronic Diseases ◽  
Chronic Urticaria ◽  
Inhaled Corticosteroids ◽  
Systemic Mastocytosis ◽  
Airway Remodeling ◽  
Clinical Manifestations ◽  
Allergic Diseases ◽  
Severe Allergic Asthma ◽  
Prophylactic Use

IgE is an immunoglobulin that plays a central role in acute allergic reactions and chronic inflammatory allergic diseases. The development of a drug able to neutralize this antibody represents a breakthrough in the treatment of inflammatory pathologies with a probable allergic basis. This review focuses on IgE-related chronic diseases, such as allergic asthma and chronic urticaria (CU), and on the role of the anti-IgE monoclonal antibody, omalizumab, in their treatment. We also assess the off-label use of omalizumab for other pathologies associated with IgE and report the latest findings concerning this drug and other new related drugs. To date, omalizumab has only been approved for severe allergic asthma and unresponsive chronic urticaria treatments. In allergic asthma, omalizumab has demonstrated its efficacy in reducing the dose of inhaled corticosteroids required by patients, decreasing the number of asthma exacerbations, and limiting the effect on airway remodeling. In CU, omalizumab treatment rapidly improves symptoms and in some cases achieves complete disease remission. In systemic mastocytosis, omalizumab also improves symptoms and its prophylactic use to prevent anaphylactic reactions has also been discussed. In other pathologies such as atopic dermatitis, food allergy, allergic rhinitis, nasal polyposis, and keratoconjunctivitis, omalizumab significantly improves clinical manifestations. Omalizumab acts in two ways: by sequestering free IgE and by accelerating the dissociation of the IgE-Fcεreceptor I complex.

Heterogeneity of mast cells in mastocytosis and inhibitory effect of ketotifen and ranitidine on indolent systemic mastocytosis

1997 ◽  
Vol 100 (6) ◽  
pp. S25-S32 ◽  
Author(s):  
Motohiro Kurosawa ◽  
Hiroo Amano ◽  
Naotomo Kanbe ◽  
Sachiko Akimoto ◽  
Yuko Takeuchia ◽  
...  
Keyword(s):  
Mast Cells ◽  
Systemic Mastocytosis ◽  
Inhibitory Effect ◽  
Indolent Systemic Mastocytosis

scholarly journals A rare case of asymptomatic solitary cutaneous mastocytoma in a child

2021 ◽  
pp. 477-479
Author(s):  
Sonam Jain ◽  
Saumya Nanda ◽  
Malvika Shastri ◽  
Divya Sethi
Keyword(s):  
Mast Cells ◽  
Young Child ◽  
Rare Case ◽  
Systemic Mastocytosis ◽  
Cutaneous Lesion ◽  
Anterior Chest Wall ◽  
Rare Tumor ◽  
Internal Organs ◽  
Cutaneous Nodule ◽  
Rare Group

Mastocytosis is a rare group of disorders occurring when mast cells diffusely infiltrate the skin or internal organs. It has two forms: Cutaneous and systemic mastocytosis. We present a case of a 12-year-old male child presenting with a reddish-brown cutaneous nodule on the anterior chest wall for 1 month. No other similar lesions were noted elsewhere. Routine hematological and radiological investigations did not reveal any abnormality. The lesion was excised, and a diagnosis of solitary cutaneous mastocytoma was made based on the clinical, histopathological, and immunohistochemical features. This case highlights the importance of diagnosing this rare tumor which can present as an asymptomatic cutaneous lesion in a young child.

A Survey on Clinical and Biological Characteristic and Therapy Management of an Italian Series of 455 Adult Patients with Systemic Mastocytosis on Behalf of Italian Registry of Mastocytosis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3188-3188
Author(s):  
Lisa Pieri ◽  
Patrizia Bonadonna ◽  
Chiara Elena ◽  
Cristina Papayannidis ◽  
Federica Irene Grifoni ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Mast Cells ◽  
Disease Progression ◽  
Myeloid Leukemia ◽  
Systemic Mastocytosis ◽  
Myeloproliferative Neoplasm ◽  
Large Series ◽  
Refractory Anemia

Abstract Systemic mastocytosis (SM) is a rare myeloproliferative neoplasm characterized by proliferation and hyperactivation of clonal mast cells. Clinical manifestations are heterogeneous and encompass cutaneous lesions, gastrointestinal alterations, osteoporosis, anaphylaxis and involvement of bone marrow and other organs due to neoplastic mast cells (MC) infiltration. As consequence, diagnosis may be difficult and patients (pts) are often evaluated by different specialists before the disease is recognized. To date, only few studies (Lim 2009, Escribano 2009, Cohen 2014) described relatively large series of pts with SM. We performed a multicentre retrospective study to evaluate clinical and biological features and therapeutic management in a large series of pts from 10 Italian centres experienced in management of SM and organized in multidisciplinary groups of specialists. We collected 455 pts diagnosed with SM according to WHO criteria. Additionally 26 pts with mastocytosis in the skin (MIS) evaluated with BM examination did not fulfil criteria for SM, leading to diagnosis of Cutaneous Mastocytosis (CM); however 2/26 pts with CM had both cKITD816V mutation and CD2/CD25 expression on MC in BM, additional 3 showed either cKITD816V or CD2/CD25. Moreover, we found 22 pts without MIS but with features of monoclonal mast cell activation syndrome. Of the 455 pts with WHO-SM (male 56%), 252 (55%) had MIS: median age at MIS diagnosis (dg) was 37 years (y) (range 0-79), while at SM dg it was 46.5 (range 18-82). Time from onset of MIS to dg of SM was 9 y (range 0-43). In 18/252 pts (7%) MIS occurred before age of 18 y (median 9, range 0-17) and persisted over childhood. Median age at dg of SM without MIS (203/455 pts, 45%) was older: 54 y, range 19-79 (p<0.0001). First manifestations of SM were MIS in 46.5% of pts, anaphylaxis in 47.8%, mediator related symptoms in 6.4%, osteoporosis/bone lesions in 5.2%, organomegaly in 3.4%, hematologic alterations in 0.4%. Anaphylaxis was observed in 76/252 (30.1%) pts with MIS, of which 23 had tryptase <20 mcg/L. BM multifocal infiltrates of MC were present in 61.6% of pts, while in 38.4% dg was performed only by using minor criteria. cKIT D816V mutation was detected in BM of 394/432 analysed pts (91.2%). Three D816V-negative pts had different cKIT mutations: M541L, D816H and K546K. In peripheral blood cKIT D816V was evaluated in 165 pts and found in 49.7%. CD2 and/or CD25 expressing MC were found in 99% of pts of the 426 evaluated. Mean tryptase value at dg was 75.9±263 mcg/L. SM subtypes were indolent SM (ISM) 402/455 (88.4%), of which 140 isolated bone marrow mastocytosis (BMM) (34.5% of ISM) and 34 smoldering SM (SSM) (8.4% of ISM), aggressive SM (ASM) 32/455 (7%), SM associated with hematological non mast cell disorders (SM-AHNMD) 20/455 (4.4%), mast cell leukemia (MCL) 1/455 (0.2%). In SM-AHNMD the associated hematologic disease was chronic myelomonocytic leukemia (6/20, 30%), non-Hodgkin lymphoma and refractory anemia with ring sideroblasts and thrombocytosis (3/20 each, 15%), essential thrombocythemia and not otherwise characterized myeloproliferative neoplasm (2/20 each, 10%), myelodysplastic syndrome, myelofibrosis, multiple myeloma and acute myeloid leukemia (AML) (1/20 each, 5%). Median follow up was 23 months (mo), range 2-289. At last follow up, 27/455 pts died (5.9%). 52% of pts had ASM, 18.5% SM-AHNMD, 14.7% SSM, 7.4% ISM and 3.7% each MCL and BMM. Causes of death were disease progression in 21/27 pts (77.8%), other solid neoplasms in 3/27 (11.1%), arterial thrombosis in 2/27 (9.5%), cerebral haemorrhage in 1/27 (3.7%). Disease progression consisted in evolution to AML in 6 pts with ASM, 1 pts with SSM and 1 pts with SM-AHNMD; median time to progression to AML was 30 mo (range 13-149); 2 pts developed other AHNMD: chronic myeloid leukemia and myelofibrosis. 178/455 pts (39%) were treated with anti MC mediators therapies. Of the 60/455 (13%) treated with cytostatic therapy 47% had ASM, 12% SM-AHNMD, 2% MCL, 35% ISM of which 38% were SSM. The ISM cohort was treated mainly due to severe osteoporosis with vertebral fractures not C-findings or disease evolution. First line therapy was interferon (28.3%), hydroxyurea (20%), midostaurine (18.3%), imatinib (13.3%), cladribin (8.3%), dasatinib (6.7%) and masitinib (5%). This is one of the largest series reporting pts with SM that may provide useful information for clinical management of pts with this probably underestimated “rare” disease. Disclosures Martinelli: Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy; ARIAD: Consultancy.

Aleukemic Mast Cell Leukemia (aMCL) - Clinical Characteristics and Outcomes

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4255-4255 ◽  
Author(s):  
Preetesh Jain ◽  
Sa Wang ◽  
Hagop M. Kantarjian ◽  
Nawid Sarwari ◽  
Keyur P. Patel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mast Cell ◽  
Mast Cells ◽  
Research Funding ◽  
Median Overall Survival ◽  
Systemic Mastocytosis ◽  
Cell Transplant ◽  
Cell Leukemia ◽  
Mast Cell Leukemia

Abstract ABSTRACT Introduction: Systemic mastocytosis (SM) is a complex and rare disease of clonal mast cells. Mast cell leukemia (MCL) is a very rare form of SM seen in <1% patients. We describe here our experience with MCL patients treated at our institution. Methods: We reviewed the medical records of 218 patients with mastocytosis who presented to our institution between 1994 and 2016. The survival of patients was calculated from the date of initial presentation to the date of last follow up. Kaplan-Meier product limit method was used to estimate the median survival. Results: From the 218 patients with mastocytosis, we identified 13 patients with MCL (6.5%). All 13 had aleukemic variant of MCL (aMCL; no presence of mast cells in blood measured by standard CBC technique but with ≥ 20% atypical mast cells in the marrow aspirate). In addition, in 4 of 13 patients, associated hematologic neoplasm (AHN) was present: 2 with myelodysplastic syndrome, 1 with chronic myelomonocytic leukemia and 1 with multiple myeloma. Median age of 13 patients was 62 years (range 24-75 years). Baseline features are summarized in Table-1. During their initial clinical presentation, 85% had constitutional symptoms, 54% had skin rash and other cutaneous symptoms, 31% gastrointestinal symptoms and 23% had joint pains. Imaging studies were performed in 6 patients: 5/6 had enlarged liver and/or spleen, 3 patients had nodal involvement, 2 had sclerotic bony lesions and 1 pt had adrenal involvement. Serum tryptase was >200 ng/ml in all the patients. Testing for c-KITD816V mutation was performed in 9 patients using mutation-specific quantitative (real-time) PCR, of which mutation was undetectable in 6 and detected in 3 patients. The sensitivity of detection was approximately 1 in 1000 mutation-bearing cells. None had FIP1L1-PDGFRA mutations. Treatments given were heterogeneous. Two patients each received imatinib with no response, 2 received dasatinib (one [positive for KITD816V mutation] had significant improvement in hepatosplenomegaly and pruritus but progressed after 1 year of dasatinib therapy), 2 cladribine based therapy with no response, and 2 with stem cell transplant and progression after it. Overall, median follow up was 111 months (1.4-131); 3 patients were alive and 9 died at the time of last follow up. Interestingly, among our 13 aMCL patients, those 4 with AHN appear to have had worse outcome: Figure-1A, shows the median overall survival (OS) of aMCL vs aMCL-AHN (32 vs 25 months; p=0.22). Overall, the median overall survival (OS) of aMCL without AHN was significantly inferior compared to aggressive systemic mastocytosis (ASM) and indolent systemic mastocytosis (ISM) without AHN: 31 months and not reached respectively (Figure-1B; p<0.001). Conclusions: In this analysis, we have shown that aMCL is very rare and these patients have very poor outcome. Based on the recent data from Gotlib et al NEJM 2016, role of midostaurin in the treatment of MCL should be explored. Further studies to characterize the genomic profile of patients with MCL are needed to identify potential therapeutic targets and disease resistance pathways. Table Survival of patients with aleukemic mast cell leukemia (aMCL) with/without AHN (A) and survival comparison of aMCL to other types of systemic mastocytosis, all without AHN (B) Table. Survival of patients with aleukemic mast cell leukemia (aMCL) with/without AHN (A) and survival comparison of aMCL to other types of systemic mastocytosis, all without AHN (B) Figure Figure. Disclosures Daver: Sunesis: Consultancy, Research Funding; Kiromic: Research Funding; Ariad: Research Funding; Pfizer: Consultancy, Research Funding; Otsuka: Consultancy, Honoraria; Karyopharm: Honoraria, Research Funding; BMS: Research Funding. Cortes:ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding. Verstovsek:Celgene: Research Funding; Bristol-Myers Squibb: Research Funding; AstraZeneca: Research Funding; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Galena BioPharma: Research Funding; Gilead: Research Funding; CTI BioPharma Corp: Research Funding; Lilly Oncology: Research Funding; NS Pharma: Research Funding; Geron: Research Funding; Promedior: Research Funding; Seattle Genetics: Research Funding; Roche: Research Funding; Pfizer: Research Funding; Genentech: Research Funding.

scholarly journals Real-World Utilization of Midostaurin Among Patients with Systemic Mastocytosis (SM)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5378-5378
Author(s):  
Ajeet Gajra ◽  
Andrew J Klink ◽  
Dhruv Chopra ◽  
Bruce Feinberg
Keyword(s):  
Mast Cells ◽  
Median Duration ◽  
Real World ◽  
Systemic Mastocytosis ◽  
Recommended Dose ◽  
Study Cohort ◽  
Cell Transplant ◽  
First Line ◽  
Line Setting

Introduction: Systemic Mastocytosis (SM) is a rare neoplasm of myeloid origin characterized by an accumulation of abnormal mast cells in the bone marrow, liver, spleen, and skin and has a molecular signature of the KITD816V mutation, detectable in >90% of patients. Clinical findings include cytopenias, liver-function abnormalities, hypoalbuminemia, weight loss, ascites, and osteolytic bone lesions due to infiltration of various organs by the malignant mast cells. The indolent and smoldering subtypes of SM can have a long natural history but aggressive systemic mastocytosis (aSM), SM with associated hematological neoplasm (SMHN), and mast cell leukemia (MCL) subtypes are associated with poor prognosis at a median survival of 3.5 years, 2 years and 6 months respectively. In April 2017, the FDA approved midostaurin, a multitargeted kinase inhibitor for the treatment of adults with aSM, SMHN and MCL at a dose of 100mg twice daily based on achievement of response rate endpoint noted in an open label trial of midostaurin (Gotlib et al, NEJM 2016). Pre-midostaurin, the treatment options for aSM, SMHN and MCL were imatinib, cladribine, interferon or allogeneic stem cell transplant (ASCT). The objective of this retrospective study was to assess the uptake and utilization of midostaurin in patients with aSM, SMHN and MCL. Methods: Patients with at least 1 claim for midostaurin (index date) between April 1, 2017 and October 31, 2018 and who had at least 1 claim with a diagnosis of SM (ICD 10 code C96.2x or C94.3x) in the 6-month pre-index period were identified from Symphony Health's Integrated Dataverse (IDV), a large US claims database containing linked longitudinal prescription, medical, and hospital claims. The IDV contains claims for 280 million active unique patients representing over 73% of specialty prescriptions, 58% of medical claims, and 30% of hospital claims volume in the US. Patients included in the study cohort had a 6-month pre-index period with no claims with a diagnosis of SM, were at least 18 years old at initiation of midostaurin, and no evidence of participation in a clinical trial. Patient characteristics and treatment patterns were summarized using descriptive statistics. Median and 95% confidence interval (CI) for duration of midostaurin were calculated using Kaplan-Meier estimates. Results: Of the 38 patients with SM treated with midostaurin, 33 had a diagnosis of aSM and 5 had a diagnosis of MCL. The majority were female (61%) with a median age of 63 years (range 27-79) at diagnosis; 42% of these patients were 65 years or older (Table). The majority (66%) of patients had commercial insurance, and patients resided in all 4 US regions (34% South, 34% West, 18% Midwest, 11% Northeast). Nearly two-thirds (63%) of midostaurin use was in the first line setting, 32% was given in second line, and 5% was given in third line. Among the 14 patients with therapy prior to midostaurin, cladribine was most common (n=4, 29%), followed by hydroxyurea, interferon alfa-2b, brentuximab vedotin, and others (each n=2, 14%). Over two-thirds (68%) had an average daily dose of 200mg on the first fill, 5% treated at 100mg daily, and 26% with average daily doses <100mg. Two thirds (22 of 33) patients with aSM and 4 of 5 with MCL were prescribed the 200mg/day recommended dose. With a median follow-up of 13.4 months from midostaurin initiation, the median duration of midostaurin 2.4 months (95% CI 1.1-4.6). Conclusions: In this retrospective claims based study, there is evidence of early uptake of midostaurin use in SM. Midostaurin was used in the first line setting in the majority of patients. The median duration of midostaurin treatment was short at 2.4 months especially when compared to a median treatment duration of 11.5 months in the pivotal trial. It is noteworthy that almost a third of patients were started on a lower than recommended dose which may compromise efficacy. The relatively short follow up may be another reason for the observed duration of response. Potential barriers to the appropriate use of midostaurin in SM such as lack of awareness, access, cost or delay in diagnosis due to its rarity will need further exploration. While the current claims-based dataset does not provide us the information, early, accurate diagnosis of SM is essential to timely utilization of midostaurin in the real-world setting. Further research and education may be needed to optimize the use of novel therapeutics in such orphan diseases. Disclosures Gajra: Cardinal Health: Employment. Klink:Cardinal Health: Employment. Chopra:Cardinal Health: Employment. Feinberg:Cardinal Health: Employment.

Idiopathic anaphylaxis

2019 ◽  
Vol 40 (6) ◽  
pp. 457-461
Author(s):  
Canting Guo ◽  
Paul A. Greenberger
Keyword(s):  
Systemic Mastocytosis ◽  
Clinical Manifestations ◽  
Panic Attacks ◽  
Serum Tryptase ◽  
C1 Esterase Inhibitor ◽  
Disease Modifying Therapy ◽  
Indolent Systemic Mastocytosis ◽  
Idiopathic Anaphylaxis ◽  
Esterase Inhibitor

Idiopathic anaphylaxis (IA) is defined as anaphylaxis without any identifiable precipitating agent or event. The clinical manifestations of IA are the same as allergen-associated (immunologic) anaphylaxis and include urticaria, angioedema, hypotension, tachycardia, wheezing, stridor, pruritus, nausea, vomiting, flushing, diarrhea, dysphagia, light-headedness, and loss of consciousness. Patients usually tend to have the same manifestations on repeated episodes. IA is a prednisone-responsive disease that is ultimately a diagnosis of exclusion. Approximately 40% of patients are atopic. Serum tryptase (or urine histamine or its metabolite) will be elevated acutely, but, if elevated in the absence of anaphylaxis, should suggest alternative diagnoses, including indolent systemic mastocytosis. A focused history, examination, and follow-up will dictate whether a patient's symptoms may be attributable to disorders that mimic anaphylaxis, such as indolent systemic mastocytosis, carcinoid syndrome, pheochromocytoma, hereditary angioedema or acquired C1 esterase inhibitor deficiency, or panic attacks. The presence of urticaria may help limit the differential diagnosis because urticaria does not usually accompany any of the above-mentioned disorders, except for indolent systemic mastocytosis. IA is classified according to the symptoms as well as the frequency of attacks. Patients who experience six or more episodes in a year, or two or more episodes in 2 months are classified as having IA-frequent (IA-F). Patients who experience fewer episodes are classified as having IA-infrequent (IA-I). This distinction is important because patients with IA-F will initially require prednisone as disease-modifying therapy, whereas most patients who with IA-I will not require prednisone. Patients with IA must carry and know when and how to self-administer epinephrine.

scholarly journals Frequency and prognostic impact of KIT and other genetic variants in indolent systemic mastocytosis

Blood ◽  
2019 ◽  
Vol 134 (5) ◽  
pp. 456-468 ◽  
Author(s):  
Javier I. Muñoz-González ◽  
Iván Álvarez-Twose ◽  
María Jara-Acevedo ◽  
Ana Henriques ◽  
Esther Viñas ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Systemic Mastocytosis ◽  
Progression Free Survival ◽  
Scoring Systems ◽  
Prognostic Impact ◽  
Limited Information ◽  
Free Survival ◽  
Pathogenic Variants ◽  
Indolent Systemic Mastocytosis

Abstract Indolent systemic mastocytosis (ISM) patients have a normal life expectancy, except in the 5% to 10% of cases that progress to more advanced SM (advSM), which has a significantly poorer outcome. Mutations in genes other than KIT frequently found in myeloid neoplasms have been associated with a poorer outcome among advSM, whereas limited information exists about their frequency and prognostic impact in ISM. We investigated the frequency and prognostic impact of variants in 18 genes, found to be altered in advSM, in 322 ISM patients (median follow-up, 5.7 years) divided into discovery (n = 200) and validation (n = 122) cohorts. Overall, 71 genetic variants were detected in 55 of 322 (17%) patients. Mutated ISM cases, particularly those carrying ASXL1, RUNX1, and/or DNMT3A (A/R/D) pathogenic variant allele frequencies (VAFs) ≥ 30%, exhibited significantly shortened (P &lt; .001) progression-free survival (PFS) and overall survival (OS). Multivariate analysis showed that serum β2-microglobulin (sβ2M) levels &gt; 2.5 µg/mL (hazard ratio [HR], 9.8; P = .001), together with a KIT D816V VAF ≥ 1% in bone marrow (BM) (HR, 10.1; P = .02) and pathogenic variants of A/R/D VAFs ≥ 30% (HR, 4.2; P = .02), were the best combination of independent predictors for PFS. In turn, A/R/D gene pathogenic VAF ≥ 30% was the only independent predictor for OS (HR, 51.8; P &lt; .001). Based on these variables, 2 scoring systems were constructed for risk stratification of ISM at diagnosis with significantly different 10-year PFS (100%, 91%, 0% for scores of 0, 1, ≥2, respectively) and OS (100% and 50% for scores of 0 and 1) rates.

scholarly journals A Retrospective Case Series Describing the Efficacy of Omalizumab in Systemic Mastocytosis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5470-5470
Author(s):  
Calum Anthony Slapnicar ◽  
Conrad Scullion Smeenk ◽  
Lisa K. Hicks ◽  
Jessica Petrucci ◽  
Peter Vadas ◽  
...  
Keyword(s):  
Mast Cells ◽  
Conflicts Of Interest ◽  
Systemic Mastocytosis ◽  
Tertiary Care ◽  
Case Series ◽  
Response To Treatment ◽  
Cutaneous Manifestations ◽  
Organ Systems ◽  
Cardiovascular Involvement

Abstract Introduction Systemic mastocytosis (SM) represents a heterogeneous group of disorders characterized by accumulation of neoplastic mast cells (MCs) in one or more organ systems. Patients with SM present with a broad range of symptoms resulting from excessive mast cell mediator release, especially histamine, that frequently overlap with those of allergic disease. Episodes of life-threatening anaphylaxis are a recognized feature of SM. Here at St. Michael's Hospital we currently follow more than 50 SM patients, the largest patient cohort in Canada. Omalizumab is a subcutaneously administered monoclonal antibody which acts on circulating IgE, reducing binding to the high-affinity IgE receptor (FCεR1) on mast cells, thereby reducing the potential reactivity of these cells. At St. Michael's Hospital, omalizumab is used as an add-on, off-label therapy in SM patients at risk for recurrent anaphylaxis. The efficacy of omalizumab treatment for SM patients remains unclear. Typically, highly symptomatic patients who are refractory to all other medication are candidates for omalizumab therapy. Objectives Our primary objective was to describe the response to treatment by omalizumab in patients with SM in a tertiary care centre. Our secondary objective was to compare the markers of disease in SM patients between those who were non-responsive versus responsive to omalizumab. The clinical and biological markers to be studied are symptoms and tryptase levels. Methods This is an observational, retrospective study (n=6) of SM patients treated with omalizumab at St. Michael's Hospital between January, 2014 and June, 2018. Electronic medical records were reviewed for mastocytosis treatment, symptom progression and tryptase levels, if available. All patients included in the study were diagnosed with SM according to the 2016 WHO criteria by undergoing a bone marrow biopsy. A baseline was established 2-5 months pre omalizumab exposure, as well as two follow-ups, each ranging from 2-8 months post omalizumab exposure (av. 4.7 months). The Brown Anaphylaxis score was used to capture severity of anaphylaxis. Mild (1), moderate (2), and severe (3) scores were associated with cutaneous manifestations, systemic (GI, respiratory, cardiovascular) involvement and systemic (hypoxia, hypotension, neurological compromise) collapse, respectively. Results Our study consisted of 4 females and 2 males, with an average age of 49 years old [IQR 36-74]. All 6 patients were diagnosed with indolent SM, the more moderate of the six SM subtypes. In every system, except for respiratory, it appears that symptoms decreased once therapy began. From baseline to first follow-up: all three patients who were experiencing systemic symptoms, three of the six manifesting cutaneous symptoms, and two of the three with cardiovascular involvement, responded fully to treatment. At second follow-up, patient 1 presented to clinic asymptomatically. Overall, 100% of patients responded to treatment with responses ranging from 17% to 100% improvement of mastocytosis-related symptoms. The grading of anaphylaxis severity reported three of the six patients improving from scores of 3 (severe) to 1 (mild). The other three patients remained at scores of 2. Patients 1 and 2 (only patients with available tryptase levels at both baseline and follow-up) saw a decrease in tryptase level from 134 to 84.1 and 11.4 to 8.3, respectively. Conclusions Omalizumab appears to be an effective therapy for patients with SM with anaphylaxis and reduces tryptase levels. It should be readily considered in the management of this population. Next steps include following these patients prospectively to better capture the efficacy of omalizumab within this population. Disclosures No conflicts of interest to declare Disclosures No relevant conflicts of interest to declare.

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