ABSTRACT
BACKGROUND: Systemic mastocytosis (SM) is a rare and potentially severe hematologic disorder characterized by the clonal proliferation of mast cells (MCs) into various organs. The clinical manifestations of advanced SM are caused by the uncontrolled release of cytokines and vasoactive amines from MC and disease-induced organ dysfunction. Patients with SM typically present with symptoms such as flushing, pruritus, diarrhea, and headaches, but outcomes following active treatment have not been well characterized. In this study, the clinical characteristics, treatment patterns, and natural history of an SM patient cohort diagnosed and treated within a community hematology network in the United States is described. METHODS: We identified 105 patients who were diagnosed and managed in one of 19 community hematology clinics up to an index date of 1 October 2022. Data collection included patient and disease characteristics, baseline biochemistry and hematology, SM diagnostic criteria being met, biomarkers tested, CD2 and/or CD25 expression in MCs as well as serum tryptase levels at presentation. Data abstraction also included supportive care drugs and anticancer therapy used, treatment response, reason for discontinuation, and overall survival by disease subtype. RESULTS: A total of 105 SM patients were identified who met the inclusion criteria. The specific SM subtypes were indolent (47.6%), aggressive (9.5%), SM with an associated hematological neoplasm (19.0%), MC leukemia (1.9%), and subtype not documented (21.9%). Regardless of subtype, approximately 62% of patients did not receive SM-directed active therapy. Only 26% of patients with indolent systemic mastocytosis (ISM) received treatment compared to 65.6% with advanced subtypes. Relative to ISM cohort, the relative risk of death in patients with the advanced SM subtypes was approximately 15 times greater (hazard ratio = 15.0; 95% confidence interval: 3.3 to 66.5). CONCLUSIONS: SM patients present with multiple underlying symptoms, within various disease subtypes that are difficult to diagnose in a timely manner. As a result, many patients do not receive active drug therapy for their disease. Therefore, greater disease awareness is required as well as new tools for earlier disease detection.
ABSTRACT
INTRODUCTION: Chronic immune thrombocytopenia purpura (ITP) in adults is a serious autoimmune disease in which platelets are prematurely destroyed, leaving the patient vulnerable to bruising and bleeding. Initial treatment is with corticosteroids. In patients who become resistant or intolerant to corticosteroids, the thrombopoietic agents (TPOs), consisting of romiplostim (ROM), eltrombopag (ELT) and avatrombopag (AVA) or the spleen tyrosine kinase inhibitor fostamatinib (FOS), are appropriate next lines of therapy. In this study, the comparative safety, effectiveness and cost of care between fostamatinib vs. the TPOs was evaluated in a real-world setting. METHODS: A retrospective analysis from 17 community hematology practices across the United States was conducted to identify adult ITP patients who received one of the four agents. Data collection consisted of patient demographics, disease characteristics, as well as number and type of prior treatments. From the first day until the end of treatment, data were also collected on platelet (PLT) counts, adverse events, the use of rescue IVIG, platelet transfusions and corticosteroids. Multivariable logistic regression analysis was used to compare PLT related endpoints between agents. RESULTS: A sample of 179 ITP patients who had received at least one of the four agents was identified. This resulted in a final sample of 51, 87, 127 and 44 patients who received FOS, ELT, ROM or AVA respectively. At month six, there were no significant differences between FOS vs. the TPOs in terms of the proportion of patients with the PLT count being ≥ 30 x 103/µL, ≥ 50 x 103/µL as well as the proportion of patients whose PLTs levels doubled relative to baseline. The frequency of thromboembolic events (TEs) was 3.9% in FOS patients compared to 9.2%, 4.7% and 11.4% in the ELT, ROM and AVA groups. The mean cost per patient with FOS was $99,209 (95%CI: $59,595 to $115,074) compared to $92,341 (95:CI$68,331 to $115,519), $108,482 (95%CI: $84,782 to $132,182) and $131,050 (95%CI: $83,327 to $179,897) for ELT, ROM or AVA respectively. CONCLUSIONS: In this real-world analysis, FOS was comparable to the TPOs in maintaining PLTs at clinically beneficial levels. Given these findings, the choice of therapy should be based on overall patient safety, preexisting risk factors for TEs and cost effectiveness.
