bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of zanubrutinib versus ibrutinib in adult patients with Waldenström macroglobulinemia in the United States.
Authors: Castillo Jorge J. , Yang Keri , Liu Rongzhe , Wang Yu , Cohen Aileen , Zimmerman Todd M. , Zhao Qian , van de Wetering Gijs , Gao Xin , Tang Boxiong 
Published: June 2021

e18856 Background: The efficacy of zanubrutinib and ibrutinib was examined in the randomized ASPEN trial (NCT03053440) in adult patients with Waldenström macroglobulinemia (WM). This analysis assessed the cost-effectiveness (CE) of zanubrutinib vs ibrutinib in this population from a US payer perspective. Methods: A 3-state (pre-progression, post-progression, and death) partitioned survival model was used to estimate the life years (LYs), quality-adjusted life years (QALYs), and costs for each treatment over a 30-year lifetime horizon. Overall survival (OS), progression-free survival (PFS), and time-to-discontinuation (TTD) curves were fitted using parametric distributions to extrapolate long-term outcomes. Selection of the parametric models for each outcome and treatment was based on assessments of 1) the proportional hazard assumption, 2) goodness-of-fit, and 3) clinical plausibility of extrapolated mean OS and associated hazard patterns (based on literature and US clinical expert input) and the alignment between PFS and TTD. Background US mortality was accounted for in the model. Utilities were based on the ASPEN EQ-5D data and literature. Costs (2020 US$) included drug (wholesale acquisition cost from RED BOOK) and adverse event management (Healthcare Cost and Utilization Project) for zanubrutinib and ibrutinib, routine care, and terminal care. Sensitivity analyses were conducted to evaluate the impact of parameter uncertainty. All outcomes were discounted at 3% annually. Results: In the base case analyses using the dependent exponential model for all outcomes over a 30-year time horizon, zanubrutinib led to 0.94 LY and 0.84 QALY gained with an additional total drug cost of $11,132. This additional cost was primarily driven by patients staying on zanubrutinib treatment longer as zanubrutinib has longer time to treatment failure. However, this is partially offset by zanubrutinib’s lower monthly drug acquisition, reduced cost of routine care (–$2,935) and terminal care (–$2,964) than ibrutinib. The incremental cost-effectiveness ratio (ICER) of zanubrutinib is $13,205 per QALY gained. The deterministic sensitivity analyses showed that ICER was most sensitive to the monthly costs of routine care. The probabilistic sensitivity analyses showed that the mean probabilistic ICER was $16,804, and that the probability of zanubrutinib being cost-effective was 61% at a willingness-to-pay threshold of $100,000 per QALY gained. Varying the time horizon to 5, 10, or 15 years consistently led to zanubrutinib being dominant (i.e., greater QALYs but lower costs). Conclusions: Zanubrutinib appears to be cost-effective compared with ibrutinib for the treatment of patients with WM in the US.[Table: see text]
Site of service trend and chemotherapy costs of commercial insured patients in 2020 compared to 2014.
Authors: Brito Rogelio Alberto , Hastings Kevin , Avalos-Reyes Elisea 
Published: June 2021

e18858 Background: Over the past decade, chemotherapy site of service has shifted from the physician’s office setting to the hospital outpatient setting. This trend has led to a concern that cancer care costs increase when patients are administered chemotherapy in the hospital outpatient setting (H) compared to a physician’s outpatient office setting (O). In 2014, we published data on the impact of site of service and chemotherapy costs. The purpose of this study is to evaluate the site of service trend and cost differential in a Commercial Insured (CI) population over time. Methods: We examined (CI) claims paid for chemotherapy by a large national payor from February 2019 through January 2020 for breast, colon, and lung cancer (BCL) patients. We then compared these changes to our July 2013 through June 2014 chemotherapy paid claims for BCL patients. Results: From February 2019 through January 2020, paid chemotherapy claims for approximately 23,000 unique patients with BCL had an increase of 23% from 2014. For all patients receiving chemotherapy with BCL, 56% received chemotherapy in the H setting and 44% received chemotherapy in the O setting. This was a significant shift from 2014 where 24% received chemotherapy in H and 76% in O settings. In 2020, the chemotherapy allowable reimbursement share was 67% for H and 33% in the O, a change from 2014 where the chemotherapy allowable reimbursement share was 34% in H and 66% in O. The overall cost per patient increased 57% from 2014 to 2020. When examining costs per patient by site of service, there was a statistically significant increase in H costs from $35,460 to $45,273 (p < 0.0001) per patient and a statistically significant increase in O costs from $21,577 to $28,270 (p < 0.0001) per patient treated in 2014 compared to 2020. Conclusions: In this study, the majority of BCL patients received chemotherapy in the H; this trend has led to substantially higher costs of care for patients treated with chemotherapy in the H compared to the O. Future studies are needed to determine the impact of clinical characteristics, genetic factors and treatment choice on these differences.
Risk factors for 30-day readmissions in patients with tumor lysis syndrome and solid malignancies: Analysis from the National Readmission Database.
Authors: Gauto Estefania , Salazar Miguel , Upadhyay Shristi , Baral Binav , Zia Maryam , Shrivastava Trilok , Cattoni Juan Adolfo 
Published: June 2021

e18863 Background: Tumor lysis syndrome (TLS) is a well-known potentially fatal complication of chemotherapy and an oncologic emergency. It is most prevalent in hematologic malignancies, but there are case reports and clinical series of occurrence after the treatment of solid tumors. Hospital readmissions are indicators of quality of care and cost control. We aim to look at the prevalence of readmissions after an initial episode of TLS in patients with solid malignancies and their financial burden on the United States healthcare system. Methods: We conducted a retrospective analysis of the 2017 National Readmission Database (NRD) of adult patients readmitted within 30 days after an initial “index” admission of TLS (ICD10 code E88.3) with a concomitant diagnosis of solid malignancy. We aimed to identify the 30-day readmission rate, mortality, healthcare-related utilization resources, and independent predictors of readmission by performing a COX regression analysis. Results: A total of 874 patients with solid tumors were admitted with TLS in 2017. The 30-day readmission rate was 20.4%. The main causes for readmission were sepsis, recurrent malignant lesions, metastasis to CNS, bleeding, acute kidney failure (AKI). Compared to initial admissions, readmitted patients were less likely to have acute kidney failure (AKI) (64.6% vs 30.8%; P < 0.01), less likely to require mechanical ventilation (17.9% vs 5.7%; P < 0.01), less likely to suffer shock (7.3% vs 2.3%; P = 0.03) and ileus (4.8% vs 0.7%; P = 0.04). Readmission was associated with higher in-hospital mortality rate (0.1% vs. 1.5%; P < 0.01), more likely to have private insurance (29.9% vs 36.1%; P < 0.01), and more likely to be discharged home (26.2% vs 36.8%; P < 0.01). The total health care in-hospital economic burden of readmission was $14.9 million in total charges to patients and $4 million in total costs for hospitals. Independent predictors of readmission were prolonged length of stay (during index admission), tobacco abuse, VTE, thrombocytopenia, and admission to an urban hospital. We identified the following preventive factors for readmission: radiation therapy, admission to a smaller hospital, total parenteral nutrition during the index admission and a primary gynecologic malignancy. Conclusions: Readmissions after TLS in patients with solid malignancy are associated with a higher in-hospital mortality rate and pose an increased health care burden. We identified risk factors that, if targeted, could lead to reducing readmissions, health care burden, and patient morbidity.
Validation of AML-Score in older adults receiving daunorubicin/cytarabine liposome intensive induction chemotherapy for treatment of secondary acute myeloid leukemia.
Authors: Schmucker Abigail , Leiby Benjamin , Wilde Lindsay 
Published: June 2021

e19000 Background: The AML-Score has been validated to predict complete remission (CR) and early mortality (EM) in patients receiving traditional induction chemotherapies but not daunorubicin/cytarabine liposome (Vyxeos; Jazz Pharmaceuticals; Palo Alto, CA). We conducted a retrospective analysis to evaluate, among patients with newly diagnosed secondary acute myeloid leukemia (sAML) who received intensive induction with daunorubicin/cytarabine liposome, how accurately the AML-Score predictions associate with observed 1) CR after intensive induction and 2) EM within 60 days after induction initiation. Methods: We abstracted demographic and clinical data from consecutive patients receiving daunorubicin/cytarabine liposome at the Sidney Kimmel Cancer Center at Thomas Jefferson University Hospital between September 2017 and November 2020. We used descriptive statistics with 95% confidence intervals (CIs) and receiver operating curves to characterize the associations between AML-Score predictions and observed rates of CR and EM. Results: In total, 40 patients were included for analysis. 27 (67.5%) were male, 27 (67.5%) were white, 36 (90.0%) were not Hispanic or Latino, and 28 (70.0%) were aged 60-72 years. Twenty-seven patients (67.5%) had a CR, and 4 (10%) experienced early mortality. Observed rates of CR and EM generally increased with increasing predicted risk (Table). The area under the curve was 0.75 (95% CI 0.60-0.90) for CR and 0.82 (95% CI 0.68-0.96) for EM. Conclusions: The AML-Score tool trends in the correct direction in terms of predicting rates of CR and EM, and thus may contribute to oncologist prognostication and treatment planning for patients receiving daunorubicin/cytarabine liposome. However, its clinical utility is limited by the fact that it may underestimate the risk of CR and overestimate the risk of EM. Further study in a larger cohort is needed to update the AML-Score to give accurate point estimates of CR and EM risk in this population. Predicted CR and EM versus Observed CR and EM.[Table: see text]
The potential treatment of antroquinonol in adult patients with relapsed acute myeloid leukemia (AML).
Authors: Wu Shou-Bao , Volodicheva Elena , Vinogradova Olga , Su Today , Cheng Howard , Chen Pei-Ni , Lin Shin-Shiou 
Published: June 2021

e19001 Background: The prognosis of relapsed acute myeloid leukemia (R/R AML) remains poor and the management is challenging. Despite the increasing availability of targeted agents, the lower responses still represent a major obstacle to overcome. Antroquinonol is an isoprenyltransferase inhibitor with antitumor activity in vitro and xenograft models of AML. Our aim is to evaluate hematopoietic recovery with Antroquinonol in this phase IIa study. Here, the results from our phase IIa trial demonstrate the safety, tolerability, and activity of Antroquinonol in patients with relapsed AML. Methods: GHAML-2-001 is a phase IIa, open-label study in adult patients with relapsed acute myeloid leukemia or at initial diagnosis when no intensive treatment is possible. Antroquinonol 200 mg BID was administered in a 28-day cycle (up to six cycles). The primary endpoint is hematologic response rate. Secondary endpoints consist of 4-week survival, 24-week survival, duration of hematologic response and transfusion independence, and the response rates. Therapy was continued for as long as tolerated and there was continuing evidence of therapeutic benefit in the opinion of the investigator. Treatment response was assessed by the International Working Group (IWG) response criteria after each cycle. Results: Twelve eligible patients had a median age of 62.5 years (range, 42-69; 6 males, 6 females) and the whole process was conducted between March 2019 and February 2020. Of the two patients who did not complete the therapy period were due to the patient's decision to withdraw: One patient withdrew on day 7 and the other one withdrew on day 49. Among other ten patients who finished all six cycles (168 days), Antroquinonol showed excellent safety and favorable tolerability. At the end of the treatment, the rate of complete remission (CR/CRi) after 6-completed cycles was 50% (5/10) and the 24-week survival rate was 100%. Transfusion independence was achieved in 8 (80%) of 10 transfusion independence evaluable patients at the end of the 6th cycle treatment. Conclusions: In high-risk relapsed AML patients, orally administered Antroquinonol induced CRs and was well tolerated. This significant result suggests the potential of Antroquinonol for the therapy of this underserved population. Clinical trial information: NCT03823352. Clinical trial information: NCT03823352.
Outcomes in AML patients receiving HMA + venetoclax combination with prior HMA exposure.
Authors: Jonathan Bakos Keegan , Blanding Dena , Rangel Christopher Andrew , Pasyar Sarah , Hill Elizabeth Goodwin , Davis James , Greenwell Irl Brian , Baratam Praneeth , Hess Brian T. 
Published: June 2021

e19011 Background: Venetoclax (Ven) is a BCL-2 inhibitor approved in combination with hypomethylating agents (HMAs) in newly diagnosed AML patients who are not candidates for intensive induction based on impressive response rates (CR+CRi of 66.4%) and median overall survival (14.7 months) compared to HMA therapy alone (DiNardo CD, NEJM, 2020). Ven was also used in combination with 10 days of a HMA (Decitabine) in a phase II study. In the subgroup of patients with relapsed AML, some of which previously received HMA, the ORR, CR+CRi, and median OS were 62%, 42%, and 7.8 months respectively. (DiNardo CD, Lancet, 2020). To our knowledge there are no studies specifically looking at patients with AML receiving HMA + Ven with previous exposure to a HMA agent. Methods: We conducted a single center retrospective study of AML patients who received HMA + Ven therapy after previously receiving a HMA agent. Baseline demographic, clinical, laboratory, pathology, and outcomes data were collected by retrospective chart review. Response criteria was determined by 2017 ELN recommendations. Kaplan Meier was constructed to summarize time to event data. Results: A total of 17 patients were identified that met these criteria. 7 patients (41%) had progressed on prior HMA treatment, 11 patients (65%) received prior intensive chemotherapy, and 5 patients (29%) received previous Allogenic SCT prior to HMA+Ven therapy. 10 patients (59%) had either a TP53 mutation or 17p deletion and 11 patients (65%) had complex cytogenetics (≥ 3 cytogenetic abnormalities). Other patient characteristics are included in table below. For the entire cohort, the ORR (CR, CRi, PR) was 41% and the CR/CRi rate was 6%; The ORR in the following subgroups for previous HMA failure, TP53 mutation/17p deletion, and complex cytogenetics were 14%, 30%, and 36% respectively. The median Progression free survival and overall survival for the entire cohort was 2 months (1-4 months 95% CI) and 3 months (1-5 months, 95% CI) respectively. 15 patients (88%) were deceased and all deaths were attributed to AML (12/15) or infection (3/15). None of the patients went on to receive an Allogenic SCT. Conclusions: Although a limited sample size which includes many patients with a TP53/17p aberration, complex cytogenetics, Allogenic SCT relapse, and/or heavily pre-treated AML, this data describes poor outcomes in patients receiving HMA+Ven after previous HMA exposure. Patients with previous HMA failure in particular had a poor response rate. None of the patients received 10 day decitabine and it is unclear if this had any effect on the results. It would be beneficial to supplement this data with experience from multiple centers. Patient Characteristics (N = 17).[Table: see text]
Perianal disease remains an understudied and difficult complication in leukemia patients.
Authors: Gupta Shreya , Patil Nirav , Steinhagen-Golbig Emily , Tomlinson Benjamin Kent , Stein Sharon , Charles Ronald 
Published: June 2021

e19016 Background: Perianal infection is a rare and poorly understood complication of patients with acute myeloid/lymphocytic leukemia (AML/ALL). With the advancements in oncology, patients are living longer in an immunocompromised state and thus bearing the inherent problems such as infections that arise with it. Perianal infection and its management impacts patients' quality of life as well as interrupts their ongoing oncologic treatment. The optimal treatment strategy for perianal infections in this highly immunocompromised group remains unclear, as does the selection and outcomes of patients for operative intervention. The aim of this study is to identify patient characteristics associated with perianal infection and to delineate outcomes in patients that undergo operative intervention. Methods: The National Inpatient Sample (NIS) database was used to identify hospitalized patients with diagnoses of perianal abscess and AML/ALL between 2007 and 2015. Patient data were weighted to obtain national estimates. Demographics and clinical characteristics were compared between patients with and without perianal disease using Rao-Scott Chi-square test for categorical variables, and weighted simple linear regression for continuous variables. Characteristics and outcomes were compared between patients who underwent operative or non-operative management. Results: There were 12,626 (0.7%) patients with perianal disease among 1,782,778 AML/ALL patient admissions. Patients with perianal disease were more likely to be younger (43.9 (42.5 – 45.3) years, p < 0.001), male (67.4% vs 32.6%, p < 0.001) and white (65.8% vs 54.8%, p < 0.001). Length of stay (18.4 days vs 9 days, p < 0.001) and hospital cost ($54K vs $25K, p < 0.001) were higher in those with perianal disease, but there was no difference in in-hospital mortality (5.5% in those with perianal diseases vs 6.2% in those without, p = 0.150). Greater proportion of patients without perianal disease were discharged to hospice (12.6% patients without perianal disease vs 5.1% patients with perianal disease, p < 0.001). Receiving a surgical intervention did not improve outcomes with respect to in-hospital mortality (5.9% operative vs 5.4 non-operative, p = 0.596), length of stay (20.2 days vs 18.2 days, p = 0.582) or hospital cost ($67K vs $53K, p = 0.525). Conclusions: Perianal disease is a rare but distressing complication in AML/ALL patients associated with longer hospital stays and higher hospital costs. Operative intervention for perianal disease did not reduce rates of in-hospital mortality, length of stay or hospital cost but it does impact the probability of discharge to hospice. Non-operative and operative intervention both remain equivocal in changing the outcomes these patients. Further studies are required to examine these associations and determine best practices for treatment of this condition in this complex patient population.
Retrospective real-world comparison of clinical and economic burden between first-generation and second-generation tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML).
Authors: Smith T. Alexander , Verma Sumit , Liu Yi , Sikirica Slaven , Janjan Nora Anita 
Published: June 2021

e19030 Background: TKIs are the standard of care for the treatment of chronic phase CML under National Comprehensive Cancer Network (NCCN) guidelines. Imatinib is recommended as a first-generation TKI (1GTKI), and bosutinib, dasatinib, nilotinib, and ponatinib are recommended as second-generation TKIs (2GTKIs). TKIs are associated with high healthcare resource utilization (HRU) and costs, although literature is limited comparing 1GTKI and 2GTKIs in a U.S. population. Methods: Using the Veteran’s Health Administration (VHA) database between April 1, 2013 and March 31, 2018, the study included patients aged ≥18 years with ≥1 medical claim for CML and ≥1 prescription claim for a TKI on or after the initial CML diagnosis date during the identification period (October 1, 2014 to September 30, 2017); the first TKI prescription claim was defined as the index date. Inverse probability of treatment weighting (IPTW) minimized potential confounding; included variables were age, race, Quan-Charlson Comorbidity Index (CCI) score, and CHA2DS2-VASc Score. Medication possession ratio (MPR) assessed adherence to index TKI; optimal adherence was defined as MPR ≥80%. Results: 944 patients were included: 78.9% on 1GTKI and 21.1% on 2GTKI. Mean age was 62.21 years (SD:18.8); 77.2% were white. At baselinetients on 1GTKI had a higher comorbidity burden than 2GTKIs: COPD (19.7% vs. 8%; p < 0.01), anemia (17.7% vs. 11.1%; p = 0.02), GI symptoms (28.5% vs. 18.6%; p < 0.01), cardiac dysrhythmias (15.6% vs. 7.5%; p < 0.01), coronary artery disease (26.3% vs. 13.6%; p < 0.01), hypertension (55.7% vs. 43.2%; p < 0.01) and CHA2DS2-VASc Score (2.2 vs 1.6; p < 0.01). Optimal adherence was higher with 1GTKI (69.6% vs. 62.2%; p = 0.04), although this was not statistically significant when mean MPR was compared. During follow-up, no difference between 1GTKI and 2GTKIs patients occurred with cardiac-related risk factors or CHA2DS2-VASc Score. Compared to 1GTKI, 2GTKIs had lower medical (inpatient and outpatient) costs ($3,162 vs. $3,906; p = 0.04) but higher all-cause pharmacy cost ($7,214 vs. $3,895; p < 0.01) due to imatinib becoming a generic drug during the study period. CML-related ($2,260 vs. $1,640, p < 0.01) and cardiac-related medical costs ($1,365 vs. $665, p < 0.01) were significantly higher in 1GTKI vs. 2GTKIs patients. Conclusions: Adherence to TKI therapy was suboptimal for both 1GTKI and 2GTKIs. 2GTKIs incurred lower medical cost in comparison to 1GTKI. Differences in total all-cause cost was primarily driven by pharmacy cost of TKIs. These results show that, beyond the cost of the TKI, using a 2GTKIs in the first-line can lead to cost offsets when compared to imatinib.
A systematic review of post-transplant lymphoproliferative disorder after liver transplant.
Authors: Haider Mobeen Zaka , Zamani Zarlakhta , Mirza Hasan Mehmood , Shahid Hafsa , Taqi Muhammad , Khalid Yousra , Mughal Mohsin Sheraz , Kiran Fnu , Kumar Deepak , Wahab Ahsan , Faisal Muhammad Salman , Mushtaq Muhammad Umair , Anwer Faiz 
Published: June 2021

e19045 Background: Post-transplant lymphoproliferative disorder (PTLD) is a complication after liver transplantation. This study aims to explore the association of PTLD with the immunosuppression, types of PTLD, clinical presentation, and outcomes. Methods: Following the PRISMA guideline, we searched the literature on PubMed, Cochrane, Embase, and clinicaltrials.gov. 1741 articles were screened and 22 studies were included. Results: Data includes 22,235 total patients who underwent a liver transplant, and 449 (2.0%) patients who developed PTLD were studied. Of the 394 patients where gender was reported, 226 were male and 168 were female. Post-transplant EBV status was positive for 63/115 (56%). 11 studies showed that the median time from transplant to the development of PTLD was 33.4 months. Among the histological types of PTLD, the monomorphic B-cell was the most common type with 127/235 (54%) cases, followed by early lesions 25/235, polymorphic 24/235, Hodgkin lymphoma 8/235, and monomorphic T-cell type 7/235. Treatment of PTLD involved reduction or cessation of the immunosuppressive drugs along with chemotherapy surgery and radiotherapy. Mortality data from 13 studies showed 68/259 (31.3%) patients died either due to PTLD or its complication. Conclusions: PTLD is rare but associated with high mortality after liver transplantation. EBV seropositivity is associated with PTLD in the majority of cases. Monomorphic PTLD is the most common type of PTLD after liver transplantation with DLBCL being the most common subtype. Abdominal symptoms and fever are among the most common symptoms. PTLD after Liver transplant a review of studies. [Table: see text]