Access to CAR T-cell therapy: Focus on diversity, equity and inclusion.

Chimeric antigen receptor T-cell (CAR T-cell) therapy has revolutionized the treatment of hematologic malignancies in patients with relapsed or refractory disease without other treatment options. However, only a very small proportion of patients with an indication for CAR T-cell can access the treatment. The imbalance between supply and demand is magnified in minority and vulnerable populations. Limited access is multifactorial and in part a result of factors directly related to the cellular product such as cost, complex logistics and manufacturing limitations. On the other hand, the impact of diversity, equity, and inclusion (DEI) and their social and structural context are also key to understanding access barriers in cellular therapy and health care in general. CAR T-cell therapy provides us with a new opportunity to better understand and prioritize this gap, a key step towards proactively and strategically addressing access. The aim of this review is to provide an analysis of the current state of access to CAR T therapy with a focus on the influence of DEI. We will cover aspects related to the cellular product and the inseparable context of social and structural determinants. Identifying and addressing barriers is necessary to ensure equitable access to this and all future novel therapies.

Provider barriers in uptake of biosimilars: case study on filgrastim.

In this article, we used administrative claims data from the OptumLabs Data Warehouse and American Hospital Association Annual Survey data to examine associations between hospital characteristics and uptake of biosimilar granulocyte colony-stimulating factor treatments. We found that 340B-participating hospitals and non-rural referral center (RRC) hospitals that reported owning rural health clinics were less likely to administer the lower-cost biosimilars, whereas the opposite was true for hospitals that are RRCs. To our knowledge, our study offers a first look at an underappreciated source of disparities in access to lower-cost medications such as biosimilars. Results from our study reveal opportunities for targeted policies to encourage adoption of lower-cost treatments, particularly among hospitals that serve rural communities where patients often have fewer choices in care site.

Financial Burden in Blood or Marrow Transplantation Survivors During the COVID-19 Pandemic: A BMTSS Report.

PURPOSE: The financial burden experienced by blood or marrow transplant (BMT) survivors during the COVID-19 pandemic remains unstudied. We evaluated the risk for high out-of-pocket medical costs and associated financial burden experienced by BMT survivors and a sibling comparison group during the COVID-19 pandemic. METHODS: This study included 2,370 BMT survivors and 750 siblings who completed the BMT Survivor Study survey during the pandemic. Participants reported employment status, out-of-pocket medical costs, and financial burden. Medical expenses ≥ 10% of the annual household income constituted high out-of-pocket medical costs. Logistic regression identified factors associated with high out-of-pocket medical costs and financial burden. RESULTS: BMT survivors were more likely to incur high out-of-pocket medical costs (11.3% v 3.1%; adjusted odds ratio [aOR], 2.88; 95% CI, 1.84 to 4.50) than the siblings. Survivor characteristics associated with high out-of-pocket medical costs included younger age at study (aORper_year_younger_age, 1.02; 95% CI, 1.00 to 1.03), lower prepandemic annual household income and/or education (< $50,000 US dollars and/or < college graduate: aOR, 1.96; 95% CI, 1.42 to 2.69; reference: ≥ $50,000 in US dollars and ≥ college graduate), > 1 chronic health condition (aOR, 2.82; 95% CI, 2.00 to 3.98), ≥ 1 hospitalization during the pandemic (aOR, 2.11; 95% CI, 1.53 to 2.89), and being unemployed during the pandemic (aOR, 1.52; 95% CI, 1.06 to 2.17). Among BMT survivors, high out-of-pocket medical costs were significantly associated with problems in paying medical bills (aOR, 10.57; 95% CI, 7.39 to 15.11), deferring medical care (aOR, 4.93; 95% CI, 3.71 to 6.55), taking a smaller dose of medication than prescribed (aOR, 4.99; 95% CI, 3.23 to 7.70), and considering filing for bankruptcy (aOR, 3.80; 95% CI, 2.14 to 6.73). CONCLUSION: BMT survivors report high out-of-pocket medical costs, which jeopardizes their health care and may affect health outcomes. Policies aimed at reducing financial burden in BMT survivors, such as expanding access to patient assistance programs, may mitigate the negative health consequences.

Healthcare Resource Utilization and Costs of Steroid-Associated Complications in Patients With Graft-Versus-Host Disease.

Acute and chronic graft-versus-host disease (aGVHD/cGVHD) are serious conditions occurring after allogeneic hematopoietic cell transplantation (HCT). Steroids are the most common first-line therapy; however, they are frequently associated with numerous morbid complications. To describe the healthcare resource utilization (HCRU) and costs of steroid-related complications in patients receiving systemic steroids for GVHD. This retrospective study used medical and pharmacy claims from the Optum Research database. Eligible patients were diagnosed with GVHD (aGVHD, cGVHD, or both) after HCT and were treated with systemic steroids between July 1, 2010, and August 31, 2019. The index date was the date of the first claim for systemic steroids after GVHD diagnosis. The baseline period was the 6 months before the index date, and the follow-up period was 2 years after the index date. Outcome variables included HCRU and costs associated with steroid complications, grouped into 4 categories: bone/muscle, gastrointestinal, infection, and metabolic/endocrine. A multivariate analysis was used to assess the cost ratio associated with the presence of each steroid complication; the linear model was adjusted for baseline patient characteristics and types of steroid conditions identified during follow-up. Another multivariate analysis assessed the hazard ratio for hospitalization associated with each steroid complication using a Cox proportional hazards regression model adjusted for the time-varying presence of each complication category. A total of 689 patients were studied (median age, 55 years; male, 60%); 22% had aGVHD only, 21% had cGVHD only, and 39% had both types of GVHD. After 2 years of follow-up, 97% had at least 1 steroid-associated complication. The most common complication category was infection (79.5%), followed by metabolic/endocrine (32.4%), gastrointestinal (29.2%), and bone/muscle conditions (19.7%). About two thirds (66%) of patients with any steroid complication had ≥1 hospitalization requiring a median (interquartile range [IQR]) of 20 (8-43) hospital days. Patients with an infection experienced the highest hospitalization rate (72%) and thus the highest associated costs. The total mean (median [IQR]) healthcare cost potentially related to steroid complications was $164,787 ($50,834 [$8865-$182,693]), and the largest expense was hospitalization (mean [median {IQR}], $140,637 [$26,782 {$0-$141,398}]). Of the different steroid complications, infections were associated with the highest cost (mean [median {IQR}], $167,473 [$57,680 {$16,261-$178,698}]). In addition, a significantly higher total adjusted cost was associated with the presence of an infection, gastrointestinal complication, or bone/muscle complication in patients with GVHD versus the absence of each complication (all P < .001). Complications occurring after steroid treatment for GVHD may add substantially to the HCRU and costs associated with GVHD management. Infections in particular required inpatient care and were associated with the highest economic burden.

The University of Minnesota's Clinical Research Support Center Feasibility Review: An objective protocol assessment carving a pathway to study success.

To successfully and efficiently initiate clinical research studies, it is critical to develop a strong, feasible, and well-written study protocol early in the start-up phase. The University of Minnesota's Clinical Research Support Center designed and implemented a structured Feasibility Review process in 2018 that addresses common start-up challenges such as poor study design, inappropriate outcomes, and limited resources. This process has been shown to turn an unfeasible study into a well-designed protocol that is IRB-approved with few protocol-related stipulations and well prepared for execution. It has also educated study teams on how to write better quality and more robust protocols for subsequent studies. Once a draft protocol is available, the entire process takes just six working days and is free of charge to investigators, study teams, and departments. From 2018-2021, one hundred sixteen Feasibility Reviews (n=116) have been completed across eight schools or colleges. Mean satisfaction scores for study team members who responded were high (N=126, M=4.71 ± 0.5) on a 5-point Likert-type scale. Most respondents (96%) indicated that they planned to modify their protocol based on reviewer feedback. Open ended/qualitative feedback was highly positive with most responses centered around the helpfulness of feasibility review, the high level of expertise, and fast turnaround time. The Feasibility Review is a valuable and multifunctional program providing timely expert guidance to study teams to efficiently and successfully launch and execute clinical research studies. It can be easily replicated, adapted, and implemented at other institutions to increase the quality and efficacy of academic research.

Site of care potentially limits cost savings from biosimilars.

OBJECTIVES: The first FDA-approved biosimilar was launched in 2015: filgrastim-sndz (Zarxio), a biosimilar for the reference drug filgrastim (Neupogen). Filgrastim is a granulocyte colony-stimulating factor used to prevent and treat neutropenia. In this study, we examined the association between site of care and drug cost across reference filgrastim, tbo-filgrastim (Granix; a version of filgrastim approved as a biosimilar in Europe and as a new drug in the United States), and biosimilar filgrastim administrations among the commercially insured. STUDY DESIGN: Retrospective study using administrative claims data. METHODS: We used OptumLabs Data Warehouse to identify the site of care of each short-acting filgrastim administration among commercial enrollees between January 1, 2014, and December 31, 2019. RESULTS: For each filgrastim product, model-adjusted median drug costs were higher in the outpatient hospital setting than for the same drug administered in the office setting. Comparing drug costs within the same setting, in the office setting, costs of biosimilar and tbo-filgrastim were $103.61 and $94.07 lower than reference filgrastim, respectively (P < .001 for each comparison). In the outpatient hospital setting, adjusted median costs for tbo-filgrastim were lower than those for reference filgrastim (-$132.90; P < .001), but adjusted median costs of the biosimilar were slightly higher ($20.50; P = .025). CONCLUSIONS: Although previous work has found lower costs for biosimilar filgrastim compared with reference filgrastim, here we found that site of care can change this calculus, reducing savings. After adjusting for patient characteristics and geography, we found that drug cost savings for biosimilar filgrastim were limited to the office setting, with no savings in the outpatient hospital setting.

Transfusion burden following reduced intensity allogeneic hematopoietic cell transplantation: Impact of donor type.

BACKGROUND: Transfusions are essential for allogeneic hematopoietic cell transplant (HCT), yet they are influenced by graft, donor, and other factors. STUDY DESIGN: We analyzed transfusions in 165 adult reduced intensity HCTs (2016-2019): HLA matched sibling donor (MSD) (n = 59), matched URD (n = 25), UCB (n = 33), and haploidentical (haplo, n = 48) detailing the cumulative incidence of platelet and RBC transfusion independence, total transfusions (day-10 to day+100) plus transfusion densities (per week) over 110 days. RESULTS: Platelet recovery to 20 × 109 /L by 6 months occurred in 39/48 (81.25%) haplo recipients (median 33 [range, 0-139]) days vs. 58/59 (98.3%) MSD (median 10 [0-37]), 21/25 (84%) matched URD (median 20 [0-153]), and 29/33 (87.87%) UCB (median 48 [29-166]) days, p < .01. Regression analysis demonstrated a lower likelihood of prompt platelet recovery in matched URD, UCB, or haplo HCTs vs. MSD. Recovery to platelet independence was quickest in MSD (median 8 days [range 0-94]), vs. URD (median 16 days [0-99]), UCB (median 57 [0-94]), or haplo (median 45 [12-97]) days, p < .01. Platelet needs were unaffected by age, conditioning, or acute GVHD. RBC transfusion independence was achieved in 78% of MSD, 64% URD, and 82% UCB, though less frequent (58%) and slowest in haplo recipients, p < .01. All haplo and UCB recipients required platelet transfusions vs. only 51% of MSD and 76% of URD. RBC needs were highest in UCB and haplo HCTs. DISCUSSION: The transplant donor influences the transfusion burden with greater platelet and RBC needs in haplo and UCB HCT which directly contributes to increased cost of care.

Healthcare resource utilization and costs among patients with steroid-resistant chronic graft-versus-host disease in the United States: a retrospective claims database analysis.

BACKGROUND: Chronic graft-versus-host disease (cGVHD) is the most serious non-relapse complication affecting long-term allogeneic hematopoietic cell transplantation (HCT) survivors. We describe healthcare resource utilization (HCRU) and costs in patients with steroid-resistant (SR) cGVHD versus no GVHD up to 360 and 720 days post-HCT. METHODS: Claims from the Optum Research Database were used to identify patients aged ≥12 years who underwent allogeneic HCT (index date) in the United States from 01 January 2010 to 31 August 2016 with diagnosis of cGVHD (within the study period or unspecified GVHD beyond 120 days post-HCT [SR defined as additional therapy ≥7 days after initiation of systemic steroids]) or no GVHD at any time. All-cause HCRU and costs were compared in patients with SR cGVHD (1-year analysis, n = 296; 2-year analysis, n = 178) versus no GVHD (1-year analysis, n = 227; 2-year analysis, n = 158). RESULTS: Most patients with SR cGVHD (75%) received ≥4 lines of therapy during follow-up. Patients with SR cGVHD had significantly more median office visits (49 vs. 27), outpatient visits (69 vs. 24), emergency department visits (1 vs. 0), and inpatient admissions (2 vs. 1) within 1 year post-HCT versus patients with no GVHD (all p<.001); HCRU was also higher in the 2-year period. Median total all-cause costs were significantly higher (p<.001) for patients with SR cGVHD versus no GVHD in the 1-year ($372,254 vs. $219,593) and 2-year ($532,673 vs. $252,909) follow-up periods. CONCLUSIONS: Patients with SR cGVHD required multiple lines of therapy and used significantly more outpatient and inpatient resources resulting in higher costs versus patients with no GVHD.

Use of Potentially Inappropriate Medications in Older Allogeneic Hematopoietic Cell Transplantation Recipients.

The use of potentially inappropriate medications (PIMs) using Beers criteria and its impact on older allogeneic hematopoietic cell transplantation (HCT) recipients is not known. Here the use of any PIMs and their therapeutic classes in reduced-intensity conditioning allogeneic HCT recipients were compared between older (≥65 years; n = 114) and younger (40 to 64 years; n = 240) patients during their initial HCT admission, defined as the number of days that a patient received 1 or more PIMs between day -14 and day +28. Poisson regression was used to determine rate ratios (RRs) in the 2 groups. In the ≥65 years group, we evaluated the impact of PIMs on Common Terminology Criteria for Adverse Events (CTCAE) grade 3-4 toxicities within 100 days and on overall mortality within 1 year post-HCT. The rate of any PIM use was similar in the older and younger groups (RR, .98; 95% confidence interval [CI], .90 to 1.06; P = .65). In terms of PIM classes, the older group had a 48% higher rate of gastrointestinal (GI) medication use (RR, 1.48; 95% CI, 1.32 to 1.65; P < .01) and a 25% higher rate of genitourinary (GU) medication use (RR, 1.25; 95% CI, 1.02 to 1.53; P = .03). Compared with males, females had a 19% higher rate of central nervous system (CNS) medication use (RR, 1.19; 95% CI, 1.03 to 1.37; P = .02) and a 30% higher rate of benzodiazepine use (RR, 1.30; 95% CI. 1.09 to 1.54; P < .01). A high-risk HCT-CI was associated with a higher rate of use of any PIMs (RR, 1.13; 95% CI, 1.01 to 1.26; P = .02), CNS medications (RR, 1.26; 95% CI, 1.04 to 1.53; P = .02) and GU medications (RR, 1.46; 95% CI, 1.09 to 1.94; P = .01). Compared with matched sibling donor HCT recipients, umbilical cord blood transplantation recipients had higher rates of GI medication use (RR, 1.32; 95% CI, 1.14 to 1.53; P < .01) and anticholinergic medication use (RR, 1.30; 95% CI, 1.06 to 1.61; P = .01). In the ≥65 years group, increasing duration of narcotic use was associated with a 1.3-fold (95% CI, 1.0 to 1.7; P = .05) higher risk of overall mortality and a 1.6-fold (95% CI, 1.02 to 2.69) greater odds of CTCAE grade 3-4 toxicities (P = .04). Our data show that older recipients (≥65 years) were as likely as their younger counterparts to receive PIMs. Among older recipients, the use of PIMs, particularly narcotics, was associated with higher mortality and higher incidence of grade 3-4 toxicities. Identifying and reducing the use of PIMs in older HCT recipients may help decrease the burden of adverse events and associated health care costs.

The Global State of Hematopoietic Cell Transplantation for Multiple Myeloma: An Analysis of the Worldwide Network of Blood and Marrow Transplantation Database and the Global Burden of Disease Study.

Multiple myeloma (MM) is a plasma cell neoplasm characterized by destructive bony lesions, anemia, and renal impairment. Access to effective therapy is limited globally. We report the rates and utilization of hematopoietic cell transplantation (HCT) globally from 2006-2015 to better characterize access to HCT for patients with MM. This was an analysis of a retrospective survey of Worldwide Network of Blood and Marrow Transplant sites, conducted annually between 2006-2015. Incidence estimates were from the Global Burden of Disease study. Outcome measures included total number of autologous and allogeneic HCTs by world regions, and percentage of newly diagnosed MM patients who underwent HCT, calculated by the number of transplants per region in calendar year/gross annual incidence of MM per region. From 2006 to 2015, the number of autologous HCT performed worldwide for MM increased by 107%. Utilization of autologous HCT was highest in Northern America and European regions, increasing from 13% to 24% in Northern America, and an increase from 15% to 22% in Europe. In contrast, the utilization of autologous HCT was lower in the Africa/Mediterranean region, with utilization only changing from 1.8% in 2006 to 4% in 2015. The number of first allogeneic HCT performed globally for MM declined after a peak in 2012 by -3% since 2006. Autologous HCT utilization for MM has increased worldwide in high-income regions but remains poorly utilized in Africa and the East Mediterranean. More work is needed to improve access to HCT for MM patients, especially in low to middle income countries. © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Geriatric assessment in older alloHCT recipients: association of functional and cognitive impairment with outcomes.

Use of allogeneic hematopoietic cell transplantation (alloHCT) is increasing in older patients with hematologic malignancies. Studies suggest that geriatric assessment (GA), incorporating functional measures such as instrumental activities of daily living (IADL), delineates subtle age-related impairments that enhance risk-stratification. The objective of this multi-institutional retrospective study was to evaluate the prognostic utility of GA metrics collected pre-alloHCT. Eligibility criteria included age ≥50 and pre-alloHCT GA inclusive of at least IADL. Beyond IADL, additional geriatric metrics were collected where available and included Medical Outcomes Study Physical Health score (MOS-PH), Timed Up and Go (TUG), and cognition by Blessed Orientation Memory Concentration (BOMC). Three hundred thirty subjects were included, with a median age of 63 (range 50 to 77). Impairments were frequent: 36% had at least 1 IADL impairment; 14% had TUG ≥13.5 seconds; and 17% had cognitive impairment (BOMC ≥ 7). Median MOS-PH score was 80. IADL and age were not significantly associated with nonrelapse mortality (NRM) or overall survival (OS). In multivariate analysis, only impaired cognition and Hematopoietic Cell Transplant-Comorbidity Index score ≥3 showed an independent association with 1-year NRM (subdistribution hazard ratio [SHR], 2.36; P = .01; and SHR, 2.19; P = .009, respectively). Cognitive impairment independently conferred inferior 1-year OS (hazard ratio, 1.94; P = .01). In a preplanned subgroup analysis in 224 patients aged ≥60 years, cognitive impairment remained the sole GA metric predictive of NRM (2-year NRM: SHR, 2.72; P = .007). These data suggest that cognitive impairment elevates risk of post-alloHCT NRM in older patients.

Healthcare resource utilization and costs associated with acute graft-versus-host disease following allogeneic hematopoietic cell transplantation.

PURPOSE: The contribution of acute graft-versus-host disease (GVHD) to healthcare resource utilization (HCRU) and costs following allogeneic hematopoietic cell transplantation (HCT) has not been extensively investigated. The objective of this study was to estimate both inpatient and outpatient HCRU and costs associated with acute GVHD during the 100-day and 1-year periods after allogeneic HCT in the USA. METHODS: A retrospective analysis of administrative claims from the Optum® Research Database of patients aged ≥ 12 years who received HCT between 2010 and 2016 was conducted. Costs and HCRU among patients with acute GVHD and no GVHD were compared during the 100-day (acute GVHD, n = 723; no GVHD, n = 385) and 360-day (acute GVHD, n = 445; no GVHD, n = 227) periods after HCT. RESULTS: Patients with acute GVHD had significantly more (P < 0.001) mean office visits (47 vs 32), hospital outpatient visits (71 vs 35), and inpatient stays (2.8 vs 1.1) than patients with no GVHD during 360 days post-HCT; similar findings were observed over the 100-day period. Mean total all-cause costs were significantly higher (P < 0.001) for patients with acute GVHD versus no GVHD during both post-HCT periods (100-day, $316,458 vs $215,229; 360-day, $466,720 vs $263,568). Additional factors associated with increased 360-day costs included young age (12-17 years; P < 0.001) and peripheral blood as graft source (P = 0.03). CONCLUSION: Acute GVHD was associated with significant HCRU and costs in the first 100 days of transplant, increasing over the first year post-HCT. Inpatient care was the primary driver, but outpatient care and related costs were also increased.

Comparison of Patient Age Groups in Transplantation for Myelodysplastic Syndrome: The Medicare Coverage With Evidence Development Study.

Importance: In 2010, the US Centers for Medicare & Medicaid Services (CMS) indicated that data regarding efficacy of allogeneic hematopoietic stem cell transplantation (HCT) in the CMS beneficiary population with myelodysplastic syndrome (MDS) were currently insufficient, but that coverage would be provided for patients enrolled in a clinical study that met its criteria for Coverage with Evidence Development (CED). Objective: The Center for International Bone Marrow Transplant Research (CIBMTR) submitted a study concept comparing the outcomes of patients aged 55 to 64 years vs aged 65 years or older who met those criteria, effectively providing coverage by CMS for HCT for MDS. Design, Setting, and Participants: Data on patients aged 65 years or older were prospectively collected and their outcomes compared with patients aged 55 to 64 years. Patients were enrolled in the study from December 15, 2010, to May 14, 2014. The results reported herein were analyzed as of September 4, 2017, with a median follow-up of 47 months. The study was conducted by the CIBMTR. It comprises a voluntary working group of more than 420 centers worldwide that contribute detailed data on allogeneic and autologous HCT and cellular therapies. Interventions: Patients with MDS received HCT according to institutional guidelines and preferences. Main Outcomes and Measures: The primary outcome was overall survival (OS); secondary outcomes included nonrelapse mortality (NRM), relapse-free survival, and acute and chronic graft vs host disease. Results: During the study period, 688 patients aged 65 years or older underwent HCT for MDS and were compared with 592 patients aged 55 to 64 years. Other than age, there were no differences in patient and disease characteristics between the groups. On univariate analysis, the 3-year NRM rate was 28% vs 25% for the 65 years or older group vs those aged 55 to 64 years, respectively. The 3-year OS was 37% vs 42% for the 65 years or older group vs the 55 to 64 years age group, respectively. On multivariable analysis after adjusting for excess risk of mortality in the older group, age group had no significant association with OS (HR, 1.09; 95% CI, 0.94-1.27; P = .23) or NRM (HR, 1.19; 95% CI, 0.93-1.52; P = .16). Conclusions and Relevance: Older patients with MDS undergoing HCT have similar OS compared with younger patients. Based on current data, we would recommend coverage of HCT for MDS by the CMS. Trial Registration: ClinicalTrials.gov identifier: NCT01166009.

Inpatient Healthcare Resource Utilization, Costs, and Mortality in Adult Patients with Acute Graft-versus-Host Disease, Including Steroid-Refractory or High-Risk Disease, following Allogeneic Hematopoietic Cell Transplantation.

Acute graft-versus-host disease (GVHD) contributes to poor outcomes following allogeneic hematopoietic cell transplantation (HCT). Data are limited regarding the economic burden of acute GVHD, particularly steroid-refractory or high-risk (SR/HR) disease. This retrospective analysis of the Premier Healthcare Database reports inpatient healthcare resource utilization (HCRU), costs, and mortality during initial hospitalization for allogeneic HCT and through 100 days post-HCT among patients who developed acute GVHD, including a subgroup with SR/HR disease, compared with patients without GVHD. The analysis included adults discharged for first HCT between January 1, 2011, and June 30, 2016 (acute GVHD, n = 906; SR/HR acute GVHD, n = 158; no GVHD, n = 1529). During the initial hospitalization for HCT, patients with acute GVHD and SR/HR acute GVHD (n = 455 and 125, respectively) had significantly longer median lengths of stay (31 and 46 days versus 24 days) and higher median total costs ($153,849 and $205,880 versus $97,417) versus patients with no GVHD (n = 1529; P < .0001 for all). During the 100-day post-HCT period, patients with acute GVHD and SR/HR acute GVHD had higher readmission rates (78.3% and 77.2% versus 28.3%; P < .0001) and inpatient mortality rates (20.2% and 35.4% versus 8.9%; P < .0001) versus patients with no GVHD. In summary, acute GVHD, especially SR/HR disease, is associated with longer inpatient stays, higher readmission rates, and higher inpatient mortality compared with no GVHD.

Biosimilar Filgrastim Uptake And Costs Among Commercially Insured, Medicare Advantage.

In 2015 the Food and Drug Administration approved filgrastim-sndz (Zarxio), the first US biosimilar. Following rapid uptake, by March 2018 filgrastim-sndz accounted for 47 percent of filgrastim administrations among commercially insured and 42 percent among Medicare Advantage beneficiaries. The initial cost difference between the originator and biosimilar was 31 percent in the former population but negligible in the latter.

Worldwide Network for Blood and Marrow Transplantation Recommendations for Establishing a Hematopoietic Stem Cell Transplantation Program in Countries with Limited Resources, Part II: Clinical, Technical, and Socioeconomic Considerations.

The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. Although this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state-of-the-art treatments, including transplantation, by providing financial, technological, legal, ethical, and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population and potentially provide long-term cost savings by circumventing the need for their citizens to seek care abroad. The costs of establishing an HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. In addition, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT, and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation for establishing HSCT programs, with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in resource-constrained settings.

Mortality, length of stay and costs associated with acute graft-versus-host disease during hospitalization for allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: Acute graft-versus-host disease (aGVHD) is a common and life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The extent to which aGVHD increases inpatient costs associated with allo-HSCT has not been thoroughly evaluated. In this analysis, mortality, hospital length of stay (LOS) and costs associated with aGVHD during allo-HSCT admissions are evaluated. METHODS: This is a retrospective analysis of discharge records from the National Inpatient Sample database for patients receiving allo-HSCT between 1 January 2009 and 31 December 2013. Allo-HSCT discharges with an aGVHD diagnosis were included in the aGVHD group and those without any graft-versus-host disease (GVHD) diagnosis comprised the non-GVHD group. Mortality, LOS and costs were compared between the two groups, as well as within subgroups, including age (<18 vs. ≥18 years) and survival status (alive vs. deceased) at discharge. RESULTS: Overall, mortality (16.2% vs. 5.3%; p < .01), median hospital LOS (42.0 vs. 26.0 days; p < .01) and median total costs ($173,144 vs. $98,982; p < .01) were significantly increased in patients with aGVHD versus those without GVHD during hospitalizations for allo-HSCT, irrespective of age group. Patients with aGVHD who were <18 years of age had a lower mortality rate but greater hospital LOS and total costs versus patients aged ≥18 years. Patients who died during allo-HSCT hospitalization had longer LOS and incurred greater costs than those who survived in both the aGVHD and non-GVHD groups. CONCLUSION: Occurrence of aGVHD during allo-HSCT admissions resulted in a tripling of the mortality rate and a near doubling of hospital LOS and total costs. In addition, death during allo-HSCT hospitalizations was associated with greater healthcare utilization and costs. Effectively mitigating aGVHD may improve survival and substantially reduce hospital LOS and costs for allo-HSCT.

Assessment of Late Mortality Risk After Allogeneic Blood or Marrow Transplantation Performed in Childhood.

Importance: Allogeneic blood or marrow transplantation (BMT) is a curative option for malignant and nonmalignant diseases of childhood. However, little is known about trends in cause-specific late mortality in this population during the past 3 decades. Objectives: To examine cause-specific late mortality among individuals who have lived 2 years or more after allogeneic BMT performed in childhood and whether rates of late mortality have changed over time. Design, Setting, and Participants: A retrospective cohort study was conducted of individuals who lived 2 years or more after undergoing allogeneic BMT performed in childhood between January 1, 1974, and December 31, 2010. The end of follow-up was December 31, 2016. Exposure: Allogeneic BMT performed in childhood. Main Outcomes and Measures: All-cause mortality, relapse-related mortality, and non-relapse-related mortality. Data on vital status and causes of death were collected using medical records, the National Death Index Plus Program, and Accurint databases. Results: Among 1388 individuals (559 females and 829 males) who lived 2 years or more after allogeneic BMT performed in childhood, the median age at transplantation was 14.6 years (range, 0-21 years). In this cohort, there was a total of 295 deaths, yielding an overall survival rate of 79.3% at 20 years after BMT. The leading causes of death were infection and/or chronic graft-vs-host disease (121 of 244 [49.6%]), primary disease (60 of 244 [24.6%]), and subsequent malignant neoplasms (45 of 244 [18.4%]). Overall, the cohort had a 14.4-fold increased risk for death (95% CI, 12.8-16.1) compared with the general population (292 deaths observed; 20.3 deaths expected). Relative mortality remained elevated at 25 years or more after BMT (standardized mortality ratio, 2.9; 95% CI, 2.0-4.1). The absolute excess risk for death from any cause was 12.0 per 1000 person-years (95% CI, 10.5-13.5). The cumulative incidence of non-relapse-related mortality exceeded that of relapse-related mortality throughout follow-up. The 10-year cumulative incidence of late mortality decreased over time (before 1990, 18.9%; 1990-1999, 12.8%; 2000-2010, 10.9%; P = .002); this decrease remained statistically significant after adjusting for demographic and clinical factors (referent group: <1990; 1990-1999: hazard ratio, 0.64; 95% CI, 0.47-0.89; P = .007; 2000-2010: hazard ratio, 0.49; 95% CI, 0.31-0.76; P = .002; P < .001 for trend). Conclusions and Relevance: Late mortality among children undergoing allogeneic BMT has decreased during the past 3 decades. However, these patients remain at an elevated risk of late mortality even 25 years or more after transplantation when compared with the general population, necessitating lifelong follow-up.

Positron Emission Tomography-Based Assessment of Metabolic Tumor Volume Predicts Survival after Autologous Hematopoietic Cell Transplantation for Hodgkin Lymphoma.

Autologous hematopoietic cell transplantation (AHCT) is curative for 60% of patients with relapsed or refractory Hodgkin lymphoma (R/R HL). A more precise assessment of the depth of remission before AHCT may help to identify patients likely to benefit from AHCT. We aimed to determine whether positron emission tomography (PET)-based quantitative parameters of total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), and maximal standardized uptake volume (SUVmax) measured before AHCT predict progression-free survival (PFS) after transplant. Pretransplant PET/computed tomography images of 96 consecutive patients with R/R HL were analyzed. Median TMTV, TLG, and SUVmax were 7.97 cm3 (range, 1.3 to 102.1), 23.7 (range, 4.0 to 813.1), and 5.23 (range, 2.7 to 23.2). Two-year PFS in patients with high TMTV (TMTVhigh; more than median; n = 17) was only 12% (95% CI, 1% to 38%) compared with 53% (95% CI, 28% to 73%; P = .05) in patients with TMTVlow (lower or equal to median; n = 17) and 63% (95% CI, 50% to 74%) in 61 patients with no metabolically active tumor (TMTV0; P > .01). In concordance, high TLG (>19) and SUVmax (>4.9) predicted inferior 2-year PFS. In multivariate analysis patients with TMTVhigh had a 3.5-fold higher risk of treatment failure compared with TMTV0/TMTVlow (HR, 3.49; 95% CI, 1.75 to 6.93; P < .01). Deauville (D)-scores of 4 to 5 before AHCT predicted worse PFS compared with D-scores of 1 to 3 (HR, 3.7; 95% CI, 1.92 to 7.28; P < .01). Yet, TMTV and D-scores were disconcordant in 12 subjects; 9 patients in the D4 group with TMTVlow had 2-year PFS of 44% (95% CI, 14% to 72%), which was 2-fold higher than predicted by D4 score. In conclusion, in patients with R/R HL and PET-positive residual disease, TMTVhigh can identify very poor AHCT responders. Patients with TMTVlow, TLG, and SUVmax before AHCT have similar outcomes to those without metabolically active disease.