bluuebunny/crossref_metadata_2025 huggingface dataset:
Dispersion in total cost of care for Medicare fee-for-service (FFS) patients with metastatic pancreatic cancer receiving FDA-approved/NCCN Category 1 regimens at 340B verus non-340B institutions.
Authors: Latimer Helen , Tomicki Samantha , Dieguez Gabriela , Cockrum Paul , Kim George P.
Published: June 2021

e18843

Background: The Department of Health and Human Services (HHS) designed the 340B drug pricing program to allow institutions that service specialty populations to acquire drugs at lower prices. Objective: To analyze the dispersion in total cost of care (TCOC) for Medicare FFS patients (pts) with metastatic pancreatic cancer (m-PANC) treated at 340B or non-340B institutions, by NCCN Category 1 regimen. Methods: We identified pts with m-PANC using ICD-10 diagnosis codes in the 2016-18 Medicare Parts A/B/D 100% Research Identifiable Files. Study pts had 2+ claims with a pancreatic cancer diagnosis and Medicare FFS coverage for 6 months pre- and 3 months post-metastasis diagnosis. Study pts were treated with NCCN Category 1 regimens: 1L gemcitabine monotherapy (gem-mono), 1L gemcitabine/nab-paclitaxel (gem-nab), 1L FOLFIRINOX (FFX), and 2L liposomal irinotecan-based regimen (nal-IRI). Pts were attributed to 340B or non-340B institutions based on plurality of chemotherapy claims. TCOC reflects insurer-paid services per line of therapy (LOT) for 3 categories: chemotherapy/supportive drugs (chemo/Rx), inpatient care (IP), and other outpatient care (OP). We grouped pts by quartile (qrt) and evaluated drivers of TCOC and mean rates of admissions (admits/pt). Results: We identified 2,697 (340B) and 3,839 (non-340B) pts taking NCCN Category 1 regimens. Gem-mono represented 1% and 4% of all pts in 340B and non-340B institutions, respectively. Gem-nab accounted for 72% of pts in both cohorts. For gem-nab, FFX, and nal-IRI pts, median TCOC was similar in both cohorts, although mean TCOC by qrt was lower at 340B institutions than non-340B institutions, except for gem-nab in the 1st qrt. The components of TCOC were similar between 340B and non-340B institutions in all qrts. In both cohorts, % IP costs increased between the 1st and 4th qrt (340B:15% to 23%, non-340B:14% to 25%). From the 1st to the 4th qrt, admits/pt increased in both cohorts. In the 340B cohort, nal-IRI pts had the lowest admits/pt while gem-nab pts had the highest in all qrts. In the non-340B cohort, nal-IRI pts had the lowest admits/pt except for in the 1st qrt. Conclusions: Median TCOC was lower at 340B institutions than non-340B institutions for all regimens, and the range of TCOC dispersion was also smaller at 340B institutions. Across qrts, chemotherapy accounted for approximately half the TCOC; however, IP costs were proportionally higher in the 4th qrt. Comparing regimens, despite 2L nal-IRI pts being more heavily pretreated, median costs in each cohort were similar to 1L gem-nab and 1L FFX, while admits/pt were generally lower than 1L gem-nab and 1L FFX across qrts and cohorts.
Cost-effectiveness of apixaban versus other direct oral anticoagulants and low-molecular-weight-heparins for cancer associated venous thromboembolism in Spain.
Authors: Muñoz Martín Andres J. , Gallardo Díaz Enrique , Crespo Carlos , Masana Domenech Roma , Soto Javier , Arumi Daniel , Fernandez Susana
Published: June 2021

e18845

Background: Venous thromboembolism (VTE) causes substantial morbidity and mortality in patients with cancer. The guidelines for the treatment of VTE in cancer patients recommend low molecular weight heparins (LMWH) and direct oral anticoagulants (DOAC) for patients where major bleeding is a low risk factor. Several studies show that DOAC represent a convenient and effective treatment option in alternative to LMWH in patients with deep-vein thrombosis or pulmonary embolism. Even though some recent studies have compared the effectiveness of DOAC vs LMWH, there is no available a cost-effectiveness analysis (CEA) comparing the relative effectiveness and cost-effectiveness of apixaban, other DOAC and. LMWH. The study aim was to conduct a CEA of apixaban (API), edoxaban (EDO), rivaroxaban (RIVA) and LMWH for the treatment of cancer associated VTE in Spain. Methods: We developed a Markov model with 12 transition health states. The model has been face-validated by two oncologists from two different Spanish hospitals. The use of resources and costs were obtained from the 2021 Spanish Ministry of Health database, and the main references for obtaining the outcomes were derived from CARAVAGGIO, HOKUSAI-VTE, ADAM VTE and SELECT-D trials. Our model yielded the effectiveness score in terms of cost per life-year (LY) gained and cost per quality-adjusted for life-year (QALY) gained. The time horizon was 12 months. We performed a deterministic and probabilistic sensitivity analysis to validate the robustness. Results: API showed the lowest 12-month cost (1943 €), and the highest amount of life years (0.79) and highest amount of QALY (0.55) gained. RIVA and EDO were less effective in terms of LY (0.76 and 0.74, respectively) and QALY (0.53 and 0.52, respectively) gained than LMWH (LY of 0.76 and QALY of 0.53), and less costly. The Incremental Cost-Effectiveness Ratio (ICER) scores in terms both of €/LY and €/QALY gained show that API is dominant over LMWH, RIVA and EDO. Conclusions: Our results suggest that API is more effective and more cost-effective than LMWH, RIVA or EDO with the 2021 Spanish healthcare costs. For interpretation of the results, reader must consider that the costs of resources analyzed in this paper may vary from country to country, and dabigatran was not included in the analysis since there are not cancer associated VTE clinical trials with dabigatran data to calculate CEA from.[Table: see text]
Bundling cancer subtypes in value-based care: A pilot analysis of lymphoma episodes in the Oncology Care Model.
Authors: Yue Andrew , Chaudhry Basit Iqbal , Schleicher Stephen Matthew , Huntington Scott F. , Lyss Aaron J. , Connor Nora , Tran Lisa , Adelson Kerin B.
Published: June 2021

e18850

Background: Value based models (VBMs) in which cancers are bundled are a growing alternative to fee for service, as in the Oncology Care Model (OCM). However, bundles in OCM may not capture the clinical granularity needed to predict resource utilization for cancer subtypes. One such bundle is lymphoma, which groups highly heterogeneous diseases with distinct treatments and differing intensity of care. Here, we compare OCM predicted episode costs (targets) to actual episode costs by lymphoma subtype. Methods: Our cohort study used OCM data from a large academic medical center (AMC) and large community oncology practice (COP). Six-month episodes of lymphoma beginning between July 2016 and June 2019 were categorized based on ICD-10 diagnoses on antineoplastic infusions and E&M visits, as well as disease and data modeling. Episodes were subdivided into follicular (FL), diffuse large B (DLBCL), small B (SBCL), mantle (MCL), Hodgkin (HL), Waldenstrom macroglobulinemia (WM), mature T/NK (T/NK), and Other. The distributional consistency of episode costs and targets for each subtype relative to the rest of the episodes was evaluated by Kolmogorov-Smirnov tests. We also compared the proportion of subtypes contributing to episodes in the AMC vs. COP. Results: A total of 1801 lymphoma episodes were identified (44% in AMC, 56% in COP). The most common subtypes (DLBCL and FL) contributed a larger proportion of episodes in the COP, while less frequent subtypes (T/NK, WM) were more prevalent at the AMC. Further, episode costs are significantly different across individual subtypes. Target variance was significantly lower than cost variance across subtypes. For example, the average target for WM was $50.4K, average costs were $40.2K, with 26% of episodes over target. In contrast, the average target for T/NK was $55.9K, average costs were $72.7K, with 64% of episodes over target. Conclusions: VBMs such as OCM currently aggregate cancer types and lack clinical granularity. Our evaluation of OCM episodes at an AMC and COP found considerable differences in lymphoma populations and in costs by subtype. Failure to account for clinical features (i.e. lymphoma history) could lead to inappropriate shifts of risk from payers to providers in VBMs.[Table: see text]
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]
Hematologic malignancy patients suffer higher mortality and morbidity from COVID-19 than solid tumor patients.
Authors: Krem Maxwell Masters , Nutalapati Snigdha , Latta Hannah L. , Thomas Chris Z. , El Haddad Hanine , Vilchez Gabriel A. , Hildebrandt Gerhard
Published: June 2021

e19048

Background: Cancer patients experience morbidity and mortality from infections, including COVID-19. Results are in conflict as to whether hematologic malignancy (heme) patients or solid tumor (solid) patients are at particular risk. We compared COVID-19 infection outcomes in these cohorts at our institution. Methods: Retrospective chart review of COVID-19 patients diagnosed from February 2020 to January 2021 who had a heme or solid diagnosis. We used Chi square analyses and t-tests for statistical correlations. Results: We analyzed outcomes of 146 COVID-19 episodes. Median age was 64 (25-97), 49% were female, and 24% were minorities. 49 (34%) had heme malignancy. Age, race, BMI, Karnofsky, and Charlson index (CCI) were similar for heme and solid cohorts. All-cause mortality (37 vs 15%) and COVID-induced mortality (33 vs 10%) were higher in heme vs solid, Table 1. Need for hospitalization (73 vs 46%, p = 0.009) and ICU care (31 vs 14%, p = 0.02) were worse for heme. Mean length of stay was 14.6 days and did not statistically differ for both groups. Overall risk of thrombosis was 11%. Severity of hypoxemia correlated with mortality. Compared with patients not requiring oxygen, relative risk (RR) of mortality was 3.06 (p = 0.06) for nasal cannula, 3.82 (p = 0.03) for high-flow oxygen, and 11.9 (p = 0.0008) for ventilation. Heme patients trended towards increased need of high-flow oxygen or ventilation vs solid patients, RR = 1.65 (p = 0.06). Additional mortality predictors were chemo within 6 months of COVID-19, age > 65, nursing home residency, CCI > 5, ICU care, max CRP > 100, ferritin > 1000, abs lymph count < 500, platelet count < 100, and bacteremia or C. difficile coinfection (Table). Race, gender, Appalachian status, and BMI did not predict mortality. Among the above factors, recent chemo (p=0.0001) and bacteremia (p = 0.03) were more common in heme vs solid patients. A higher proportion of heme patients received treatment for COVID-19 (51 vs 32%, p = 0.03). The most frequent therapies across the whole group were steroids (n=43), remdesivir (n=29), and azithromycin (n = 17). Conclusions: COVID-19 poses elevated mortality and morbidity risk for hematologic malignancy vs other cancer patients despite similar pre-infection demographics. Not surprisingly, need for ICU care, age, recent chemotherapy, and comorbidities elevate mortality risk in both heme and solid patients. Elevated inflammatory markers and severe lymphopenia appear to identify those patients who have immune dysregulation and greatest mortality risk. Mortality predictors.[Table: see text]
Serious infections and cardiovascular complications among patients with chronic lymphocytic lymphoma treated with first-line ibrutinib or bendamustine/rituximab.
Authors: Irwin Debra E. , Thompson Stephen , Ribalov Rinat , Choudhry Azhar
Published: June 2021

e19503

Background: Clinical trials have shown positive outcomes associated with ibrutinib monotherapy (IM) and bendamustine / rituximab combination (BR) therapy in patients with chronic lymphocytic lymphoma (CLL) compared to other standard treatments, but limited real-world data exist. This study evaluated serious infections and cardiovascular complications in CLL patients treated with first-line IM or BR therapy using US real-world data. Methods: Administrative claims from the MarketScan® Research Databases were used to identify adult patients enrolled in commercial or Medicare supplemental insurance plans based on a first prescription fill of IM or BR therapy (the index date) from 2/1/14 to 9/1/19. Patients were diagnosed with CLL, treatment naïve, and continuously enrolled for ≥12 months prior to and following the index date. Serious infections and cardiovascular complications requiring hospitalization (diagnosis code in any position) were evaluated during a fixed 12-month follow-up period. Statistical differences in outcome distributions between the treatment groups were tested. Multivariate logistic regression models for lower respiratory tract infection (LRTI) and atrial fibrillation (AF) were also conducted to determine the adjusted odds of hospitalization. Results: Of 2,138 CLL patients, 810 had IM and 512 had BR as index therapy with ≥12 months of follow-up data. Patients receiving IM were older and more likely to have had an LRTI during baseline compared to BR patients, otherwise both groups had similar baseline characteristics. Hospitalization for serious infections was more common during follow-up among IM patients than BR patients (17.7% vs. 13.1%; p = 0.027). Specifically, 10.2% of IM patients had a bacterial infection hospitalization compared to 5.7% of BR patients (p = 0.004) and 10.7% of IM patients had a LRTI hospitalization compared to 6.6% of BR patients (p = 0.012). After adjusting for baseline characteristics, IM patients did not have significantly higher odds of a LRTI hospitalization (OR = 1.51; p = 0.069). Hospitalization for cardiovascular complications was more common during follow-up among IM patients than BR patients (18.3% vs. 11.9%; p = 0.002). Specifically, 8.4% of IM patients had an AF-related hospitalization versus 2.7% of BR patients (p < 0.001). After adjusting for baseline characteristics, IM patients were more likely to have a hospitalization for AF versus BR patients (OR = 3.89; p < 0.001). Conclusions: In a real-world setting, serious infections and cardiovascular complications were more common among CLL patients treated with first-line IM compared to BR during 12 months of follow-up. IM patients were more likely than BR patients to have an inpatient admission due to AF after adjusting for other patient characteristics.
Preliminary results of the phase 2 study of zanubrutinib in patients with previously treated B-cell malignancies intolerant to ibrutinib and/or acalabrutinib.
Authors: Shadman Mazyar , Sharman Jeff Porter , Levy Moshe Y. , Porter Ryan , Zafar Syed Farhan , Burke John M. , Chaudhry Arvind , Freeman Benjamin Bruce , Misleh Jamal Ghazi , Yimer Habte Aragaw , Cultrera Jennifer L. , Guthrie Troy H. , Kingsley Ed , Rao Subramanya S. , Chen Dih-Yih , Cohen Aileen , Feng Shibao , Huang Jane , Flinn Ian
Published: June 2021

e19506

Background: Many patients (pts) with B-cell malignancies require continuous treatment with Bruton tyrosine kinase inhibitors (BTKi). Adverse events (AEs) are a common reason for ibrutinib (ibr) or acalabrutinib (acala) discontinuation. Early data from BGB-3111-215 showed zanubrutinib (zanu) was well tolerated in pts with B-cell malignancies intolerant to ibr or acala. We report preliminary results with a median follow-up of 4.2 mo. Methods: Pts meeting protocol criteria for intolerance to ibr, acala or both (without documented progressive disease) were given zanu monotherapy (160 mg twice daily or 320 mg once daily). Recurrence of AEs that led to intolerance of prior BTKi and additional safety measures were assessed based on the Common Terminology Criteria for AEs v5.0. Investigators determined responses using disease status at study entry as baseline. Results: As of November 1, 2020 (cutoff), 44 pts (n=34 chronic lymphocytic leukemia/small lymphocytic lymphoma, n=6 Waldenström macroglobulinemia, n=2 mantle cell lymphoma, n=2 marginal zone lymphoma) were enrolled, received ≥1 dose of zanu, and analyzed for safety. Median age was 70.5 y (range, 49-91); median duration of treatment was 4.2 mo (range, 0.1-12.6). Median number of prior regimens was 2 (range, 1-12). Regarding prior BTKi, 39 pts received ibr only, 4 received ibr and acala, and 1 received acala only. The median number of ibr- or acala-intolerant AEs per pt was 2 (range, 1-5). 83% of ibr and 78% of acala intolerant events did not reccur on zanu; Table. At data cutoff, 43 pts remained on treatment; 1 withdrew consent due to zanu-unrelated grade 3 syncope. Overall, 34 pts (77.3%) reported any AE; most commonly reported AEs were myalgia (n=9; 20.5%), contusion (n=8; 18.2%), dizziness (n=7; 15.9%), fatigue (n=7; 15.9%), and cough (n=5; 11.4%). Grade ≥3 AEs were reported in 6 pts (13.6%), serious AEs in 1 pt (2.3%, febrile neutropenia and salmonella infection), AEs requiring dose interruptions in 6 pts (13.6%), and AEs leading to dose reduction in 2 pts (4.5%). No AEs led to zanu discontinuation. No deaths were reported. All efficacy evaluable pts (26/26 [100%]) maintained (10 [38.5%]) or achieved deepening (16 [61.5%]) of their response. Conclusions: Zanu provides an additional treatment option after intolerance to other BTKi, demonstrating tolerability and sustained or improved efficacy. Updated results will be presented. Recurrence and Severity Change of AEs Leading to Ibr or Acala Intolerance. Clinical trial information: NCT04116437. [Table: see text]
The impact of atrial fibrillation on hospitalization outcomes for patients with chronic lymphocytic leukemia: A large database analysis.
Authors: Ammad Ud Din Mohammad , Thakkar Samarthkumar , Patel Harsh P. , Hussain Syed Ather , Zafar Aneeqa , Liaqat Hania , Shah Zunairah , Ganatra Sarju , Mushtaq Muhammad Umair , Anwer Faiz
Published: June 2021

e19508

Background: With the increased use of novel agents like Bruton tyrosine kinase inhibitors (BTKi) for the treatment of chronic lymphocytic leukemia (CLL), the incidence of atrial fibrillation (AF) is on the rise in these patients. However, the excess burden added by AF to the morbidity and mortality of CLL patients is unclear. Methods: Using the appropriate ICD-9 and ICD-10 codes, the National Inpatient Sample (NIS) database was accessed to gather data of hospitalized CLL patients with AF from 2008 to 2019. Propensity-score matching (PSM) and logistic regression model were performed to control for baseline patient factors like age, sex, income, and the relevant co-morbidities to match 7265 CLL patient admissions with AF and 7265 CLL patient admissions without AF. The primary outcome was all-cause mortality (ACM), while secondary outcomes included stroke, acute heart failure (AHF), and total cost of hospital stay. Results: The mean age of the cohorts was 82 years. Females made up 44% of both groups. The AF group had similar prevalence of systemic hypertension (62.38% vs 62.10%; p= 0.73), diabetes mellitus (5.09% vs 5.43%; p= 0.35), congestive heart failure (5.57% vs 5.36%; p= 0.58), valvular heart disease (1.17% vs 1.44%; p= 0.14), and pulmonary hypertension (0.21% vs 0.14%; p= 0.31) compared to the group without AF. PSM revealed CLL patients with AF had a higher rate of ACM (6.06% vs 4.47%; p= <0.0001), AHF (7.50% vs 3.85%; p= <0.001), and stroke (3.09% vs 1.65%; p= <0.0001). Admission in the AF group also had a higher median total cost of hospital stay ($9097 vs $7646). A logistic regression model was done to adjust for confounders which revealed similar results for the AF group with increased adjusted odd’s ratio (aOR) of ACM (aOR:1.39, 95% confidence interval (CI): 1.19-1.61; p= <0.001), AHF (aOR: 2.16, 95% CI: 1.85-2.52; p= <0.001), and stroke (aOR:1.94, 95% CI: 1.54-2.44; P= <0.001) (Table). Conclusions: Our data suggest that hospitalized CLL patients with AF are at a significantly increased risk of all-cause mortality, AHF, and stroke. Several limitations like the inability to establish the temporal relationship between CLL and AF and the lack of data regarding medications of individual patients are important to keep in mind while interpreting the results.[Table: see text]
Outreach: Preliminary safety and efficacy results from a phase 2 study of lisocabtagene maraleucel (liso-cel) in the nonuniversity setting.
Authors: Godwin John E. , Mattar Bassam Ibrahim , Maris Michael B. , Bachier Carlos R. , Stevens Don A. , Hoda Daanish , Varela Juan Carlos , Cherry Mohamad , Fanning Suzanne R. , Essell James H. , Yimer Habte Aragaw , Courtright Jay G. , Sharman Jeff Porter , Trede Nikolaus S. , Youssef Marina , Lymp James , Shaughnessy Paul
Published: June 2021

e19513

Background: Concerns about adverse events (AEs) related to CAR T cell therapy have resulted in administration of this therapy largely in an inpatient setting. OUTREACH (NCT03744676) evaluates safety and efficacy of liso-cel in patients (pts) with R/R large B-cell lymphoma (LBCL) across inpatient and outpatient settings at nonuniversity medical centers (NMCs). Methods: NMCs, including centers naïve to CAR T cell therapy, enrolled adults with R/R LBCL in this open-label, multicenter study. Eligible pts had R/R PET-positive disease after ≥2 lines of prior systemic therapy, ECOG PS ≤1, and adequate organ function. Prior autologous HSCT was allowed. Pts received sequential infusions of equal target doses of CD8+ and CD4+ cells at a total target dose of 100 × 106 CAR+ T cells. Primary endpoint was incidence of grade (G) ≥3 cytokine release syndrome (CRS) graded per 2014 Lee criteria, neurological events (NEs), prolonged cytopenias (Day 29 G ≥3 lab values), and infections. Secondary endpoints were safety and overall response rate (ORR). Outpatient AE monitoring/management was managed by a multidisciplinary CAR T cell therapy team following standard operating procedures (SOPs). Results: At data cutoff, 46 pts (inpatients n = 16, outpatients n = 30) were treated with liso-cel. Inpatients and outpatients had similar demographics and baseline disease characteristics; median age was 63 y (range, 34–83), 63% had diffuse LBCL not otherwise specified, and 91% were refractory to last therapy. Safety data were similar across inpatients and outpatients (Table). Early (study Day ≤4) and overall hospitalization in outpatients was reported in 27% and 63%, respectively; median time to hospitalization was 5 (2–61) days and median length of stay was 6 (1–28) days. For efficacy-evaluable pts (n = 44), ORR was 75% for inpatients and 79% for outpatients; CR rates were 50% and 61%, respectively. Conclusions: Liso-cel was successfully administered to pts with R/R LBCL in the outpatient setting and pts were monitored for CAR T cell therapy–related toxicities by multidisciplinary teams using SOPs. The incidences of severe CRS and NEs and use of tocilizumab and/or corticosteroids were similar in inpatients and outpatients, and consistent with the pivotal study observations (Abramson, The Lancet 2020). Updated data with longer follow-up will be presented. Clinical trial information: NCT03744676. [Table: see text]