Treatment Patterns and Healthcare Resource Utilization of Patients With Paroxysmal Nocturnal Hemoglobinuria: A Retrospective Claims Data Analysis.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disorder commonly treated with complement inhibitors such as eculizumab, ravulizumab, and pegcetacoplan. This study aims to describe treatment patterns, healthcare resource utilization, and cost for newly diagnosed PNH patients in 2 large, health insurance claims databases: MarketScan and Optum. Among the 271 patients meeting the inclusion criteria in MarketScan, 57.9% were female, and the average age was 46.6 years. Among these newly diagnosed patients, 25.1% (n = 68) of patients received a PNH-specific pharmacologic treatment, and the average time from diagnosis to treatment was 4.7 months. The medication possession ratio was 97.0%, but discontinuation was common (58.8%). The average per-patient-per-month costs were $18,978, driven by pharmacy and infusion ($11,182), outpatient ($4086), and inpatient ($3318) costs. Despite the availability of multiple treatments, 39.9% of patients had an inpatient stay, and 50.9% had an emergency department visit. Better care management and the introduction of new treatment options are needed to address delays between diagnosis and treatment, and high rates of hospitalization and emergency department use among patients with PNH.

Paroxysmal nocturnal hemoglobinuria: Review of the patient experience and treatment landscape.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder caused by complement-mediated hemolysis and thrombosis through the alternative pathway. The most common symptom of PNH is fatigue due to chronic anemia, which can negatively impact quality of life (QoL) and affect overall well-being. The currently approved therapies for PNH significantly limit intravascular hemolysis (IVH) and reduce the risk of thrombosis; however, they are associated with an infusion schedule that can become burdensome, and not all patients experience complete disease control. Several new complement inhibitors are in development that address the need for convenient routes of administration and aim to provide better disease control. With the variety of new treatment options on the horizon, hematologic markers as well as QoL concerns, patient opinion, and lifestyle factors should be considered to choose the optimal PNH treatment for each specific patient.

Hematopoietic Stem-Cell Transplant Utilization in Relapsed/Refractory Hodgkin Lymphoma: A Population-Level Analysis of Statewide Claims Data.

PURPOSE: Although hematologic malignancies affect adults of all ages, few data exist on the real-world patterns of care for patients younger than 65 years in the United States. Understanding patterns of care from diagnosis through relapsed disease may provide insight about care across community and academic centers. We used a large statewide claims database to describe the path of Hodgkin lymphoma (HL) treatment among adults age < 65 years at diagnosis. METHODS: We defined a cohort of commercially insured patients with HL who underwent hematopoietic stem-cell transplantation (HSCT) from 2009 to 2013 in the Massachusetts All-Payer Claims Database (APCD). The primary goals of our study were to accurately identify patients and their treatment patterns who had relapsed/refractory HL and underwent HSCT. We also characterized time to treatment failure and overall survival. RESULTS: A total of 7,613 patients had International Classification of Diseases, Ninth Revision, diagnostic codes for HL. From our algorithm, we identified 117 patients as part of the final cohort who underwent autologous and/or allogeneic HSCT. Median age was 39.0 years and 50.4% were female. Initial therapy was identified for 68 of the 117 patients (58.1%). Most (> 74.4%) of the identified transplants were autologous, and 19 patients (16.2%) underwent allogeneic transplant, with or without prior autologous transplant. Of the 68 patients with initial therapy data, the median time to HSCT after completion of initial treatment was 223.5 days (Q1 = 151.5, Q3 = 414.5). CONCLUSION: We used the Massachusetts APCD to create a cohort of patients age < 65 years with relapsed/refractory HL. Our findings support the use of APCD for the large-scale analysis of patient characteristics, treatment patterns, and outcomes for young adult patients with hematologic malignancies.

Characterization and prognosis of temozolomide-induced aplastic anemia in patients with central nervous system malignancies.

BACKGROUND: Temozolomide-induced aplastic anemia (TIAA) is a rare but highly challenging complication of temozolomide (TMZ) therapy. Evidence describing prognosis, clinical characteristics, and treatment of this entity is very limited. METHODS: We performed a multicenter, 22-year observational cohort study of patients with central nervous system (CNS) malignancies treated with temozolomide who developed TIAA, retrospectively analyzing prognosis, complications, and recovery. TIAA was defined using adapted evidence-based severe aplastic anemia criteria incorporating profound cytopenias and a minimum duration (4 weeks) without hematologic recovery. RESULTS: Of 3821 patients with CNS malignancies receiving TMZ, 34 patients (0.89%) met criteria for TIAA. Onset was rapid, with 29 patients (85.3%) developing TIAA before completing a second TMZ cycle. 23 patients (67.6%) ultimately achieved a hematologic recovery. Patients without recovery were more likely to develop febrile neutropenia (72.7% vs. 30.4%, P = .03), infectious complications (45.5% vs. 8.7%, P = .02), require hospitalization (81.8% vs. 43.5%, P = .04), and die (100.0% vs. 60.9%, P = .02). Median overall survival from TIAA diagnosis was 752 days in patients achieving a partial hematologic recovery versus 28 days in those who did not (P < .0001). 29 patients (85.3%) received one or more hematopoietic growth factors; hematologic recovery rates were higher in patients receiving thrombopoietin receptor agonists (81.8% vs. 60.9%) but were not higher in patients receiving granulocyte colony-stimulating factors. CONCLUSIONS: TIAA occurs in <1% of patients receiving TMZ for CNS malignancies, but is highly morbid when it occurs and frequently fatal in the one-third of patients not achieving hematologic recovery. Thrombopoietin receptor agonists may improve the likelihood of a hematologic recovery.

Multiorgan failure in a fatal case of autoimmune hemolytic anemia.

BACKGROUND: Autoimmune hemolytic anemia (AIHA) results in red blood cell destruction by auto-antibodies directed against surface antigens and is rarely fatal. Here we describe a case of AIHA, refractory to both standard and experimental therapies, complicated by multiorgan failure, and rapidly leading to death. CASE REPORT AND RESULTS: A 65 year-old man who presented with progressive dyspnea and jaundice was found to have hemolytic anemia. Diagnostic work-up revealed a positive direct antiglobulin test and a strong pan-reactive antibody in the plasma reacting to a titer of 1:1024 with strongest reactivity at 37 °C Coombs' phase with reagent anti-IgG. The red cell eluate contained a pan-agglutinin. The patient received multiple lines of treatment including glucocorticoids, intravenous immunoglobulin, rituximab, eculizumab, splenectomy and etoposide. Despite these interventions, he continued to experience brisk hemolysis and remained transfusion dependent. Repeat testing on day 16 demonstrated persistent high titer IgG auto-antibodies, suggesting minimal suppressive effect of therapy. His course was complicated by acute renal and liver failure, venous thrombosis, and worsening coagulopathy, and he ultimately died from multiorgan failure on day 18. CONCLUSION: Severe cases of AIHA can result in multiorgan failure and a fatal outcome. The rapid development of liver failure in this setting has been described in only few case reports to date, and represents an important complication for clinicians to be aware of when treating patients with AIHA.

COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection.

Patients with coronavirus disease 2019 (COVID-19) have elevated D-dimer levels. Early reports describe high venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) rates, but data are limited. This multicenter retrospective study describes the rate and severity of hemostatic and thrombotic complications of 400 hospital-admitted COVID-19 patients (144 critically ill) primarily receiving standard-dose prophylactic anticoagulation. Coagulation and inflammatory parameters were compared between patients with and without coagulation-associated complications. Multivariable logistic models examined the utility of these markers in predicting coagulation-associated complications, critical illness, and death. The radiographically confirmed VTE rate was 4.8% (95% confidence interval [CI], 2.9-7.3), and the overall thrombotic complication rate was 9.5% (95% CI, 6.8-12.8). The overall and major bleeding rates were 4.8% (95% CI, 2.9-7.3) and 2.3% (95% CI, 1.0-4.2), respectively. In the critically ill, radiographically confirmed VTE and major bleeding rates were 7.6% (95% CI, 3.9-13.3) and 5.6% (95% CI, 2.4-10.7), respectively. Elevated D-dimer at initial presentation was predictive of coagulation-associated complications during hospitalization (D-dimer >2500 ng/mL, adjusted odds ratio [OR] for thrombosis, 6.79 [95% CI, 2.39-19.30]; adjusted OR for bleeding, 3.56 [95% CI, 1.01-12.66]), critical illness, and death. Additional markers at initial presentation predictive of thrombosis during hospitalization included platelet count >450 × 109/L (adjusted OR, 3.56 [95% CI, 1.27-9.97]), C-reactive protein (CRP) >100 mg/L (adjusted OR, 2.71 [95% CI, 1.26-5.86]), and erythrocyte sedimentation rate (ESR) >40 mm/h (adjusted OR, 2.64 [95% CI, 1.07-6.51]). ESR, CRP, fibrinogen, ferritin, and procalcitonin were higher in patients with thrombotic complications than in those without. DIC, clinically relevant thrombocytopenia, and reduced fibrinogen were rare and were associated with significant bleeding manifestations. Given the observed bleeding rates, randomized trials are needed to determine any potential benefit of intensified anticoagulant prophylaxis in COVID-19 patients.

Masitinib in treatment of pancreatic cancer.

INTRODUCTION: Pancreatic cancer continues to have high mortality despite the development of many chemotherapeutic agents. The 5-year relative survival for stage IV patients is less than 3%. This urgent unmet need warrants the development of novel and active therapeutic agents, which focus both on targeting cancer cells and modifying the microenvironment of cancer cells. Areas covered: In this article, the authors review the development of masitinib, a novel tyrosine kinase inhibitor of numerous targets, including c-Kit, PDGFR and FGFR. This review covers its development from the bench to clinical trials assessing its potential in pancreatic cancer. Expert opinion: While masitinib has not shown an increase in overall survival (OS) or progression free survival (PFS) compared to the current standard of care in patients with pancreatic adenocarcinoma, masitinib may have a role in decreasing inflammation related to those patients with increased pain scores with pancreatic adenocarcinoma. If we have the tools to identify accurate subgroups of patients who may benefit from particular therapies, this agent may be of benefit to these patients. Indeed, if more sophisticated biomarkers and the identification of patient subgroups are better explained, the authors believe that masitinib will become part of the armamentarium against pancreatic adenocarcinoma.