Household income and health-related quality of life in children receiving treatment for acute myeloid leukemia: Potential impact of selection bias in health equity research.

OBJECTIVE: Examine the influence of household income on health-related quality of life (HRQOL) among children with newly diagnosed acute myeloid leukemia (AML). DESIGN: Secondary analysis of data prospectively collected from pediatric patients receiving treatment for AML at 14 hospitals across the United States. EXPOSURE: Household income was self-reported on a demographic survey. The examined mediators included the acuity of presentation and treatment toxicity. OUTCOME: Caregiver proxy reported assessment of patient HRQOL from the Peds QL 4.0 survey. RESULT: Children with AML (n = 131) and caregivers were prospectively enrolled to complete PedsQL assessments. HRQOL scores were better for patients in the lowest versus highest income category (mean ± SD: 76.0 ± 14 household income <$25,000 vs. 59.9 ± 17 income ≥$75,000; adjusted mean difference: 11.2, 95% CI: 2.2-20.2). Seven percent of enrolled patients presented with high acuity (ICU-level care in the first 72 h), and 16% had high toxicity (any ICU-level care); there were no identifiable differences by income, refuting mediating roles in the association between income and HRQOL. Enrolled patients were less likely to be Black/African American (9.9% vs. 22.2%), more likely to be privately insured (50.4% vs. 40.7%), and more likely to have been treated on a clinical trial (26.7% vs. 18.5%) compared to eligible unenrolled patients not enrolled. Evaluations of potential selection bias on the association between income and HRQOL suggested differences in HRQOL may be smaller than observed or even in the opposing direction. CONCLUSIONS: While primary analyses suggested lower household income was associated with superior HRQOL, differential participation may have biased these results. Future studies should partner with patients/families to identify strategies for equitable participation in clinical research.

Development of a risk assessment model for cardiac injury in patients newly diagnosed with acute myeloid leukemia based on a multicenter, real-world analysis in China.

BACKGROUND: Studies have revealed that acute myeloid leukemia (AML) patients are prone to combined cardiac injury. We aimed to identify hematological risk factors associated with cardiac injury in newly diagnosed AML patients before chemotherapy and develop a personalized predictive model. METHODS: The population baseline, blood test, electrocardiogram, echocardiograph, and genetic and cytogenetic data were collected from newly diagnosed AML patients. The data were subdivided into training and validation cohorts. The independent risk factors were explored by univariate and multivariate logistic regression analysis respectively, and data dimension reduction and variable selection were performed using the least absolute shrinkage and selection operator (LASSO) regression models. The nomogram was generated and the reliability and generalizability were verified by receiver operating characteristic (ROC) curves, the area under the curve (AUC) and calibration curves in an external validation cohort. RESULTS: Finally, 499 AML patients were included. After univariate logistic regression, LASSO regression and multivariate logistic regression analysis, abnormal NT-proBNP, NPM1 mutation, WBC, and RBC were independent risk factors for cardiac injury in AML patients (all P < 0.05). The nomogram was constructed based on the above four variables with high accuracy. The area under the curve was 0.742, 0.750, and 0.706 in the training, internal validation, and external validation cohort, respectively. The calibration curve indicated that the model has good testing capability. The Kaplan-Meier curve showed that the higher the risk of combined cardiac injury in AML patients, the lower their probability of survival. CONCLUSIONS: This prediction nomogram identifies hematological risk factors associated with cardiac injury in newly diagnosed AML patients and can help hematologists identify the risk and provide precise treatment options.

Elderly patients with acute myeloid leukemia who only receive supportive care in the Surveillance, Epidemiology and End Results-Medicare database: demographics, treatment patterns and outcomes.

Aim: Elderly acute myeloid leukemia (AML) patients are often not treated with antileukemic therapy due to their poor overall health condition, leaving supportive care as the sole treatment option. Objective: To evaluate patient characteristics, treatment patterns and outcomes of elderly patients with AML who are treated with supportive care only. Methods: A retrospective analysis of elderly AML patients included in the Surveillance, Epidemiology and End Results-Medicare database from 2008 to 2015. Results: Of elderly patients with AML (n = 7665), 3209 (41.9%) received supportive care only. Their mean age was 79 years, 50.5% were males; 48.2% died during the first 3 months and 67.3% died during the first 6 months. 82.2% died within the first year; only 13.2% survived >12 months. 77.9% patients died due to leukemia. Conclusion: In elderly AML patients treated with supportive care only, older age, concurrent hypertension, chronic obstructive pulmonary disease, chronic kidney disease and acute myocardial infarction were identified as prognostic factors associated with decreased likelihood of survival. Ideally, these patients should be treated with antileukemic therapy in addition to supportive care, as most of them die from disease progression.

This study analyzed data on elderly patients with acute myeloid leukemia (AML) who were only treated with supportive care. The source of this data was the Surveillance, Epidemiology and End Results (SEER)-Medicare database. Of the 7665 patients diagnosed with AML during 2008­2015, 3209 (41.9%) received supportive care only. Their mean age at index date was 79 years; slightly more than half of these were males (50.5%). Almost half of these patients (48.2%) died within the first 3 months and approximately two-thirds (67.3%) died within the first 6 months. Only a small proportion (13%) of these patients were alive after 1 year. These patients who were alive after one were likely to be in remission (there was decrease in the signs and symptoms of AML). The results of this study showed that elderly AML patients who only received supportive care were more likely to die early if they also had chronic kidney disease, chronic obstructive pulmonary disease, history of acute myocardial infarction or hypertension. As elderly AML patients may be in poor general health and have other diseases (comorbidities), this could be the reason why they may not be treated with antileukemic therapy. Instead of treatment with supportive care only, these patients should ideally receive antileukemic therapy in addition to supportive care. More research should be done to find alternate treatments for these elderly AML patients.

Characteristics and outcomes of elderly patients with acute myeloid leukemia who receive no treatment in the Surveillance, Epidemiology and End Results-Medicare database.

Background: Without treatment, acute myeloid leukemia (AML) is rapidly fatal. Nevertheless, a large proportion of elderly AML patients do not receive any treatment. Aim: To characterize the demographics, comorbidities, survival and prognostic factors of elderly AML patients who do not receive any AML treatment or supportive care (SC). Methods: A retrospective cohort analysis of the Surveillance, Epidemiology and End Results-Medicare database (2008-2015). Results: Of 7665 AML patients, 2373 (31%) did not receive any AML treatment or SC. The mean age was 80.4 years, 52.8% were males and 79.7% and 95.3% died within the first 60 and 180 days, respectively; 2.1% survived >12 months and only 5.5% of patients had remission or relapse codes populated. Conclusion: Older age, male gender, concurrent depression, ischemic heart disease, chronic kidney disease and benign prostatic hyperplasia were associated with a decreased likelihood of survival. Multiple factors contribute to the complex clinical status of these patients preventing intensive chemotherapy; they should still ideally be treated, at least with the best SC.

An analysis of the data collected in the Surveillance, Epidemiology and End Results-Medicare database from 2008 to 2015 was performed. This database includes data collected by a national cancer registry on people diagnosed with cancer in the United States and those who enroll in Medicare. This study focused on acute myeloid leukemia (AML) patients who did not receive any AML treatment or supportive care (SC). Of 7665 patients with AML, 2373 (31%) did not receive any AML treatment or SC. At the time the data was indexed for each patient in the database, their mean age was 80.4 years and around 53% were males. Within the first 60 days, around 80% of these patients died; over 95% died within the first 180 days. Only 2% of patients survived more than a year without treatment; these patients were likely in remission. Without treatment, AML patients who were older, were male or who also had depression, ischemic heart disease, chronic kidney disease or benign prostatic hyperplasia had a higher chance of dying early. There could be many reasons why these patients are not treated. The main reasons are their poor health condition and the presence of two or more health conditions in a patient at the same time (comorbidities). However, they should still ideally be treated, at least with the best SC. Additional treatment options are urgently needed for elderly AML patients who have comorbidities and are in poor general health.

A Co-Management Model for Myeloid Malignancies That Evolved during the COVID-19 Pandemic.

INTRODUCTION: Myeloid malignancies are a heterogeneous group of clonal bone marrow disorders that are complex to manage in the community and therefore often referred to subspecialists at tertiary oncology referral centers. Many patients do not live in close proximity to tertiary referral centers and are unable to commute long distances due to age, comorbidities, and frailty. Interventions that minimize the travel time burden without compromising quality of care are an area of unmet need. We describe a cancer care delivery model for patients with myeloid malignancies that is built around telehealth and enables this vulnerable population access to care at an NCI-designated cancer center while receiving majority of their care close to home. METHODS AND MATERIALS: We report on a cohort of patients with myeloid malignancies who were co-managed by a general community oncologist and an academic leukemia subspecialist at Montefiore Einstein Cancer Center in New York. Patients were initially referred to our institute for a second opinion by community practices that are in partnership with Montefiore Health System, and initial visits were in-person or via telehealth. Treatment plans were made after discussion with patient's local community oncologist. Patients then continued to receive majority of their treatment and supportive care including transfusion support with their local oncologist, and follow-up visits were mainly via telehealth with the academic leukemia subspecialist. RESULTS: Our cohort of 12 patients had a median age of 81 years (range, 59-88 years). Patients remained on active treatment for a median time of 357 days (range, 154-557 days). Most of our patients had a performance status of ECOG 2 or higher. Three patients had myelodysplastic syndromes, 7 patients had acute myeloid leukemia, and 2 patients had myelofibrosis. The median number of hospitalizations over the total treatment time period was one. CONCLUSION: We demonstrate a shared academic and community care co-management model for the treatment of myeloid malignancies in elderly, frail patients using telehealth as a backbone with a very low hospitalization rate.

Economic Impact of Transformation to Acute Myeloid Leukemia Among Actively Managed Patients with Higher-Risk Myelodysplastic Syndromes in the United States.

INTRODUCTION: Transformation of higher-risk myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML) may be associated with increased healthcare resource utilization (HCRU) and costs. To describe this economic impact, HCRU and costs were compared between US patients who experienced transformation to AML and those who did not. METHODS: Using the Optum administrative claims data, this retrospective matched cohort study identified patients (≥ 18 years old) with higher-risk MDS who initiated first-line therapy between January 1, 2008, and June 30, 2019. Patients whose disease transformed to AML were matched 1:1 to patients whose disease did not transform, based on the duration of follow-up. The follow-up period was divided into two periods: pre- (before transformation to AML) and post-AML (after transformation to AML). For patients who did not transform to AML, pre- and post-AML periods were determined using the transformation date of their matched pair. HCRU and total adjusted costs (2019 US dollars, $) were compared between patients who transformed to AML and those who did not. RESULTS: A total of 118 matched patient pairs were included in the study. The hospitalization rate was significantly higher in patients who transformed than in those who did not during the entire follow-up (58.8% vs. 44.1%; P = 0.0295) and post-AML (47.5% vs. 28.0%; P = 0.0028) periods. Across all periods, supportive care use was significantly higher among patients who transformed to AML vs. patients who did not transform. Adjusted mean monthly costs for patients with higher-risk MDS who transformed to AML were higher than those who did not transform ($25,964 vs. $19,150; P < 0.0001). The observed total cost difference was more notable in the post-AML period ($36,424 vs. $14,860; P < 0.0001). CONCLUSIONS: Patients with higher-risk MDS whose disease transformed to AML incurred significantly higher healthcare costs compared to those whose disease did not transform, highlighting the important need for treatments that prevent or delay transformation.

Global, national, and regional burden of acute myeloid leukemia among 60-89 years-old individuals: insights from a study covering the period 1990 to 2019.

Background: Our study examined the global, national, and regional trends in the incidence, mortality, and disability-adjusted life years (DALYs) associated with older people's acute myeloid leukemia (AML) over a 30 years period. AML, which predominantly affects individuals aged 60-89, is known for its severity and unfavorable prognosis. By providing insights into the growing burden of AML, our research highlights the urgent need for effective interventions and support at various levels. Methods: In this study, we analyzed older people with AML aged 60-89 using the Global Burden of Disease (GBD) database for 2019. Our goal was to assess trends and characteristics by examining the incidence rate, mortality rate, DALYs, and estimated annual percentage change (EAPC). We aimed to provide a comprehensive understanding of the disease's trajectory and development. Results: In 2019, the older age group of 60 to 89 years reported 61,559 new cases of AML, with the corresponding number of deaths being 53,620, and the estimated DALYs standing at 990,656. Over the last 30 years, the incidence rate of AML in this age bracket increased by 1.67 per 100,000 people, the mortality rate rose by 1.57 per 100,000 people, and the rate of DALYs, indicative of disease burden, climbed by 1.42 per 100,000 people. High Socio-demographic Index (SDI) regions, particularly high-income North America and Australia, had the highest incidence rates. Germany had the highest incidence rate among the 204 countries analyzed, while Monaco reported the highest mortality and DALY rates. Smoking, high body mass index, occupational exposure to benzene, and formaldehyde were identified as significant risk factors associated with mortality from older people with AML in 2019. Conclusion: Our study showed that the incidence, mortality, and DALY rates of AML in the older population were strongly correlated with the SDI, and these rates have been steadily increasing. This had become an increasingly serious global health issue, particularly in areas with a high SDI. We highlighted the urgency to focus more on this disease and called for the prompt implementation of appropriate preventive and control measures.

Enhancing Administrative Claims Data: Feasibility, Validation and Application of Linking Medicare Claims Data and National Marrow Donor Program Search Data.

PURPOSE: Administrative claims data provide real-world service utilization of acute myeloid leukemia (AML) treatment, but lacks insight into treatment delays or barriers. The National Marrow Donor Program (NMDP)/Be The Match Search (Search) data contains information on donor search, but lacks information on treatment received if allogeneic hematopoietic cell transplant (HCT) is not performed. We hypothesized that linking these two data sets would create a rich resource to define factors associated with receiving HCT that could not be evaluated with either data set alone. METHODS: A subset of 2010-2016 Medicare administrative claims data was linked with Search data. A total of 5,351 patients with AML age 65-74 years (HCT = 607, no HCT = 4,744) were identified using Medicare. These patients were then linked to 93,800 records with a donor search between 2009 and 2016. Patient date of birth, sex, disease, ZIP code, transplant center/hospital, and diagnosis date were used for matching. Exploratory analysis was conducted to identify predictors associated with receiving HCT for patients with AML who received a search. RESULTS: The data sets were successfully linked, showing high sensitivity and specificity. The final cohort included 5,085 patients with AML (HCT = 533, no HCT = 4,552). Of 97 patients who received HCT without a matched search, more than 85% received a related donor HCT. Of those not receiving HCT, 609 had a matched NMDP search and 3,943 did not have a matched NMDP search. Multivariate analysis showed time to search, age, diagnosis year, race/ethnicity, and neighborhood education status associated with receiving HCT. CONCLUSION: Methods herein demonstrate the feasibility of linking Search and Medicare data. Similar methods may be applied to answer critical questions regarding barriers to HCT, thereby identifying areas to improve access to care.

Treatment Pattern, Financial Burden, and Outcomes in Elderly Patients with Acute Myeloid Leukemia in Korea: A Nationwide Cohort Study.

Although approximately 50% of patients with acute myeloid leukemia (AML) are diagnosed over the age of 60 years, there is currently no established consensus on the treatment of elderly AML patients. Herein, we aimed to explore the incidence, medical expenditure, treatment, and outcomes of elderly AML patients in Korea by analyzing a nationwide cohort. We employed the Korean National Health Insurance Service-Senior cohort, which represents 10% of a random selection from a total of 5.5 million subjects aged 60 years or older. AML patients were identified according to the main diagnostic criteria of acute leukemia. Treatment for AML was divided into high- (high-dose cytarabine ± idarubicin) and low- (low-dose cytarabine or hypomethylating agents) intensity chemo-therapy and classified according to the chemotherapeutics protocol. We analyzed the survival outcomes and medical expenditures. Among 558,147 elderly patients, 471 were diagnosed with AML, and 195 (41.4%) were treated with chemotherapy. The median age was 65 years, and the median overall survival (OS) was 4.93 months (95% confidence interval, 4.47-5.43). Median OS was longer in patients undergoing chemotherapy than those in the best supportive care group (6.28 vs. 3.45 months, p < 0.001), and the difference was prominent in patients aged < 70 years. Twenty-eight (5.9%) patients received high-intensity chemotherapy, while 146 (31.0%) received low-intensity chemotherapy. The difference in median OS according to dose intensity was 4.6 months, which was longer in the high-intensity chemotherapy group (9.8 vs. 5.2 months in low-intensity group); however, the difference was not statistically significant. Patients who received high-intensity chemotherapy recorded longer hospital stays and incurred greater expenses on initial hospitalization. Elderly AML patients in Korea exhibited clinical benefits from chemotherapy. Although patients should be carefully selected for intensive treatment, chemotherapy, including low-intensity treatment, can be considered in elderly patients. Moreover, prospective studies on new agents or new treatment strategies are needed.

The epidemiology, treatment patterns, healthcare utilizations and costs of Acute Myeloid Leukaemia (AML) in Taiwan.

BACKGROUNDS: An increasing incidence of Acute Myeloid Leukaemia (AML) has been reported in several Western countries. However, the epidemiology of AML in Asia is very limited. According to the National Comprehensive Cancer Network (NCCN) guideline of AML, a range of conventional therapy options is available to AML patients. Nevertheless, different treatment strategies may result in diverse healthcare utilization and costs. Understanding the treatment patterns, healthcare utilization and costs of AML would thus be essential for clinicians and policymakers to optimize the treatment strategies of AML. OBJECTIVES: The objective of this study was to investigate the incidence, treatment patterns, healthcare utilization and costs of AML in Taiwan using a nationwide population database. METHODS: We retrospectively identified AML patients diagnosed from 2006 to 2015 from the Taiwan Cancer Registry Database (TCRD) and estimated the epidemiology of AML in Taiwan. The TCRD was linked to National Health Insurance Research Database (NHIRD) to collect the treatment patterns and health care utilization. Patients diagnosed with AML from 2011 to 2015 were further identified to analyze treatment patterns, healthcare utilization and costs. RESULTS: The crude annual incidence of AML increased from 2.78 to 3.21 cases per 100,000 individuals from 2006 to 2015. However, the age-standardized rate (ASRs) of AML slightly declined from 2.47 to 2.41 cases per 100,000 individuals in the same period. Among 2,179 AML patients who received induction therapy (median age: 56 years), most of them (n = 1744; 80.04%) received standard-dose cytarabine (SDAC) regimen. The remaining 162 patients received high dose cytarabine (HDAC) and 273 patients received non-standard dose cytarabine (N-SDAC) regimen as the induction therapy. The median medical costs in our study for patients treated with chemotherapy alone was $42,271 for HDAC, $36,199 for SDAC and $36,250 for N-SDAC. For those who received hematopoietic stem cell transplantation (HSCT) after induction therapy, their median medical costs were $78,876 for HDAC, $78,593 for SDAC and $79,776 for N-SDAC. CONCLUSIONS: This study is the first population-based study conducted in Asia to provide updated and comprehensive information on epidemiology, treatment patterns and healthcare resource utilization and costs of AML.

Treatment patterns, economic burden, and overall survival in US Medicare Advantage beneficiaries newly diagnosed with acute myeloid leukemia (AML) in 2015-2020.

The present study assessed changes in patient management, economic burden, and overall survival (OS) in a contemporary cohort of 2775 US Medicare Advantage beneficiaries aged ≥66 years newly diagnosed with acute myeloid leukemia (AML) between 01 January 2015 and 30 June 2020. Use of venetoclax-based therapy increased and replaced hypomethylating agent (HMA) monotherapy as the most common first-line treatment choice in 2019-2020. In newly diagnosed AML patients aged ≥75 and 66-74 years, mean per-patient 1-year healthcare expenditures were $81,818 and $156,033 (2020 USD) and median OS was 2.3 and 8.5 months, respectively. In addition, 40% of Medicare Advantage patients with newly diagnosed AML continue to receive supportive care alone. These findings indicate that at the population level clinical outcomes remain poor for older adults with AML, pointing to a continuing unmet medical need.

The long shadow of socioeconomic deprivation over the modern management of acute myeloid leukemia: time to unravel the challenges.

Biological and non-biological variables unrelated to acute myeloid leukemia (AML) preclude standard therapy in many settings, with "real world" patients under-represented in clinical trials and prognostic models. Here, using a case-based format, we illustrate the impact that socioeconomic and anthropogeographical constraints can have on optimally managing AML in 4 different healthcare systems. The granular details provided, emphasize the need for the development and targeting of socioeconomic interventions that are commensurate with the changing landscape of AML therapeutics, in order to avoid worsening the disparity in outcomes between patients with biologically similar disease.

Estimating the Productivity Impact of Acute Myeloid Leukemia in Australia Between 2020 and 2029, Using a Novel Work Utility Measure: The Productivity-Adjusted Life Year (PALY).

PURPOSE: Acute myeloid leukemia (AML) is a rare hematologic malignancy accounting for 0.8% of new cancer diagnoses in Australia. High mortality and morbidity affect work productivity through workforce dropout and premature death. This study sought to estimate the productivity loss attributable to AML in the Australian population over 10 years and to estimate the costs of this productivity loss. Productivity was measured using productivity-adjusted life years (PALYs), a similar concept to quality-adjusted life years, but adjusts for the productivity loss attributable to disease, rather than impaired health. MATERIALS AND METHODS: Dynamic life tables modeled the Australian working population (age 15-65 years) between 2020 and 2029. The model population had two cohorts: those with and without AML. Differences in life years, PALYs, and costs represented the health and productivity impact of AML. Secondary analyses evaluated the impact of different scenarios. RESULTS: Over the next 10 years, there will be 7,600 years of life lost and 7,337 PALYs lost because of AML, amounting to Australian dollars (AU$) 1.43 billion in lost gross domestic product ($971 million in US dollars). Secondary analyses highlight potential savings of approximately AU$52 million if survival rates were improved by 20% and almost AU$118 million in savings if the return-to-work rates increased by 20% on the current estimates. CONCLUSION: Our study demonstrates that even in low-incidence cancer, high mortality and morbidity translate to profound impacts on years of life, productivity, and the broader economy. Better treatment strategies are likely to result in significant economic gains. This highlights the value of investing in research for improved therapies.

Ethnic and border differences on blood cancer presentation and outcomes: A Texas population-based study.

BACKGROUND: The Texas/Chihuahua (US/Mexico) border is a medically underserved region with many reported barriers for health care access. Although Hispanic ethnicity is associated with health disparities for many different diseases, the population-based estimates of incidence and survival for patients with blood cancer along the border are unknown. The authors hypothesized that Hispanic ethnicity and border proximity is associated with poor blood cancer outcomes. METHODS: Data from the Texas Cancer Registry (1995-2016) were used to investigate the primary exposures of patient ethnicity (Hispanic vs non-Hispanic) and geographic location (border vs non-border). Other confounders and covariates included sex, age, year of diagnosis, rurality, insurance status, poverty indicators, and comorbidities. The Mantel-Haenszel method and Cox regression analyses were used to determine adjusted effects of ethnicity and border proximity on the relative risk (RR) and survival of patients with different blood cancer types. RESULTS: Hispanic patients were diagnosed at a younger age than non-Hispanic patients and presented with increased comorbidities. Whereas non-Hispanics had a higher incidence of developing blood cancer compared with Hispanics overall, Hispanics demonstrated a higher incidence of acute lymphoblastic leukemia (RR, 1.92; 95% CI, 1.79-2.08; P < .001) with worse outcomes. Hispanics from the Texas/Chihuahua border demonstrated a higher incidence of chronic myeloid leukemia (RR, 1.28; 95% CI, 1.07-1.51; P = .02) and acute myeloid leukemia (RR, 1.17; 95% CI, 1.04-1.33; P = .0009) compared with Hispanics living elsewhere in Texas. CONCLUSIONS: Hispanic ethnicity and border proximity were associated with a poor presentation and an adverse prognosis despite the younger age of diagnosis. Future studies should explore differences in disease biology and treatment strategies that could drive these regional disparities.

Healthcare resource utilization in adult patients with relapsed/refractory FLT3 mutated acute myeloid leukemia: A retrospective chart review from Spain.

BACKGROUND: Information regarding impact on healthcare systems of relapsed or refractory (R/R) FLT3 mutated (FLT3mut) acute myeloid leukemia (AML) is scarce. OBJECTIVE: To assess the time and reimbursement associated with hospitalizations of patients with R/R FLT3mut AML in a tertiary Spanish hospital. METHODS: Retrospective review of medical charts identified patients aged ≥ 18 years with R/R FLT3mut AML between 1998 and 2018. Data were collected from the date of first diagnosis of R/R FLT3mut AML (index) until death or loss to follow-up. The primary end point was duration and frequency of hospitalization, use of outpatient resources and transfusion burden. Reimbursement associated with hospitalizations (including associated chemotherapy) was also assessed. RESULTS: Thirty-eight patients were eligible for inclusion. Their median age was 52 years, and 30 (79%) received intensive salvage chemotherapy; FLAG-IDA-based regimens were the most frequent (24 patients, 63%). Overall, there were 150 hospitalizations (mean 3.9/patient; mean duration 21 days). Patients spent a mean of 24% of the study period in hospital. Total mean reimbursement was €108 293 per patient; the majority (€89 834) attributable to inpatient stays (€22 576 /hospitalization). During chemotherapy period (prior to first alloHSCT), there were 73 hospitalizations (mean duration 22 days); mean reimbursement was €19 776 per hospitalization and €49 819 per patient. AlloHSCT (n = 16) involved 77 hospitalizations (mean duration 21 days), mean reimbursement €25 231/hospitalization and €131 515 per patient. CONCLUSION: Data from this study suggest that there is a substantial healthcare resource utilization and cost burden on R/R FLT3mut AML patients in Spain receiving active treatments.

Asia-inclusive global development of pevonedistat: Clinical pharmacology and translational research enabling a phase 3 multiregional clinical trial.

The investigational NEDD8-activating enzyme inhibitor pevonedistat is being evaluated in combination with azacitidine versus single-agent azacitidine in patients with higher-risk myelodysplastic syndrome (higher-risk MDS), higher-risk chronic myelomonocytic leukemia (higher-risk CMML), or low-blast acute myeloid leukemia (AML) in a Phase 3 trial PANTHER. To support Asia-inclusive global development, we applied multiregional clinical trial (MRCT) principles of the International Conference on Harmonisation E17 guidelines by evaluating similarity in drug-related and disease-related intrinsic and extrinsic factors. A PubMed literature review (January 2000-November 2019) supported similarity in epidemiology of higher-risk MDS, AML, and CMML in Western and East Asian populations. Furthermore, the treatment of MDS/AML was similar in both East Asian and Western regions, with the same dose of azacitidine being the standard of care. Median overall survival in MDS following azacitidine treatment was generally comparable across regions, and the types and frequencies of molecular alterations in AML and MDS were comparable. Dose-escalation studies established the same maximum tolerated dose of pevonedistat in combination with azacitidine in Western and East Asian populations. Pevonedistat clearance was similar across races. Taken together, conservation of drug-related and disease-related intrinsic and extrinsic factors supported design of an Asia-inclusive Phase 3 trial and a pooled East Asian region. A sample size of ~ 30 East Asian patients (of ~ 450 randomized) was estimated as needed to demonstrate consistency in efficacy relative to the global population. This analysis is presented as an exemplar to illustrate application of clinical pharmacology and translational science principles in designing Asia-inclusive MRCTs. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Azacitidine is the standard of care for myelodysplastic syndromes/low-blast acute myeloid leukemia (AML) across Western and East Asian patients. The first-in-class small-molecule inhibitor of NEDD8-activating enzyme, pevonedistat, has been investigated as a single agent in multiple studies of hematologic and nonhematologic malignancies and in combination with azacitidine in elderly patients with untreated AML. WHAT QUESTION DID THIS STUDY ADDRESS? By applying clinical pharmacology and translational science and International Conference on Harmonisation E17 principles, this study designed an East Asian-inclusive global pivotal Phase 3 trial of pevonedistat, taking into consideration drug-related and disease-related intrinsic and extrinsic factors. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? These analyses provide scientific rationale for Asia-inclusive globalization of the pivotal, Phase 3 PANTHER trial and for pooling clinical data across the East Asian region for assessing consistency in efficacy. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? We developed a framework to facilitate efficient global clinical development of investigational therapies for rare cancers and orphan diseases in Asia-inclusive multiregional clinical trials.

When hematologic malignancies meet COVID-19 in the United States: Infections, death and disparities.

Scientific data is limited on the risks, adverse outcomes and racial disparities for COVID-19 illness in individuals with hematologic malignancies in the United States. To fill this void, we screened and analyzed a nation-wide database of patient electronic health records (EHRs) of 73 million patients in the US (up to September 1st) for COVID-19 and eight major types of hematologic malignancies. Patients with hematologic malignancies had increased odds of COVID-19 infection compared with patients without hematologic malignancies for both all-time diagnosis (malignancy diagnosed in the past year or prior) (adjusted Odds ratio or AOR: 2.27 [2.17-2.36], p < 0.001) and recent diagnosis (malignancy diagnosed in the past year) (AOR:11.91 [11.31-12.53], p < 0.001), with strongest effect for recently diagnosed acute lymphoid leukemia (AOR: 31.03 [25.87-37.27], p < 0.001), essential thrombocythemia (AOR: 20.65 [19.10-22.32], p < 0.001), acute myeloid leukemia (AOR: 18.94 [15.79-22.73], p < 0.001), multiple myeloma (AOR: 14.21 [12.72-15.89], p < 0.001). Among patients with hematologic malignancies, African Americans had higher odds of COVID-19 infection than Caucasians with largest racial disparity for multiple myeloma (AOR: 4.23 [3.21-5.56], p < 0.001). Patients with recently diagnosed hematologic malignancies had worse outcomes (hospitalization: 51.9%, death: 14.8%) than COVID-19 patients without hematologic malignancies (hospitalization: 23.5%, death: 5.1%) (p < 0.001) and hematologic malignancy patients without COVID-19 (hospitalization: 15.0%, death: 4.1%) (p < 0.001).

Access to Therapy for Acute Myeloid Leukemia in the Developing World: Barriers and Solutions.

PURPOSE OF REVIEW: Acute myeloid leukemia (AML) is a costly disease, and its impact is greater in developing countries (DC). We will review the current concept of what are DC, compare the differences in the epidemiology and economic burden of this disease between developed and DC, and finally, analyze the barriers and possible solutions that DC should implement to achieve better results. RECENT FINDINGS: DC is a frequently misunderstood name. The way we use to measure human development is changing, and multidimension metrics better define what are DC. With this in mind, we show the differences in the AML epidemiology and the impact of economic burden in DC. We analyze the barriers to access therapy from a clinician point of view, to show that most DC shared similar challenges but with a diverse healthcare structure. Finally, we provide several possible solutions for a more integrated and timely treatment that allows better results not only in terms of survival but with a better quality of life. The economic burden of AML treatment in DC is high, and the results are poor. It is crucial to face this challenge and propose new treatment approaches to achieve better results.

Epidemiology, management, and economic impact of acute myeloid leukemia and myelodysplastic syndrome in Spain at the hospital level: a claims database analysis.

OBJECTIVES: This study reviewed patient characteristics, management, and medical costs of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs) in Spanish hospitals. METHODS: Data were extracted from the Spanish Ministry of Health records via a claims database containing patient records from 192 private and 313 public hospitals between 1997 and 2015 for AML, and 2008 and 2015 for MDS. Direct medical costs at the hospital level were calculated based on mean medical procedure costs determined per the Spanish Ministry of Health. RESULTS: Records for 39,568 patients with AML and 33,091 with MDS were analyzed. The median age of AML patients was 65 years (interquartile range (IQR) = 27) and of MDS patients was 81 years (IQR = 12). In terms of disease management, 58% and 83% of admissions were due to emergencies for patients with AML and MDS, respectively; median length of hospital stay was 14 days (IQR = 25) for AML and seven days (IQR = 9) for MDS. There was an increase in allogeneic hematopoietic stem cell transplantations over time for patients with AML or MDS. Mean annual direct medical costs of AML and MDS, respectively, were €66,422,245 and €42,635,313 for total costs, and €30,775 and €10,312 per patient. Of the total costs, transplantations contributed total annual costs of €15,843,982 and €2,705,791 for patients with AML and MDS, respectively. CONCLUSIONS: This study provides novel data to assist decision makers in allocating resources. AML and MDS represent a significant burden for the National Spanish Healthcare System, with substantial costs incurred in secondary care, principally associated with the increasing number of transplantations.