bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of potential drug-drug interactions among nonmetastatic castration-resistant prostate cancer patients treated with apalutamide and enzalutamide.
Authors: Appukkuttan Sreevalsa , Fu Chunmay , Du Yuxian , Cha Ashley , Parkin Jacqueline , Gaiser Andrew , Partridge Jamie , Kong Sheldon , Freedland Stephen J.
Published: June 2021

e18690

Background: Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) are often treated with concurrent medications for the management of comorbid conditions. This increases the risk of drug interactions which may lead to compromised efficacy and safety of nmCRPC therapies. This study aimed to characterize potential drug-drug interactions (pDDIs) with the novel anti-androgen (AA) agents enzalutamide (Enza) and apalutamide (Apa) in a real-world nmCRPC population. Methods: We analyzed Optum Clinformatics Data Mart, a large claims database from January 1, 2017, through March 31, 2020. The study population included adult males with prostate cancer, evidence of castration, >1 pharmacy claim for Apa or Enza (index date defined as drug initiation), and without codes for metastases. Darolutamide, a more recently approved AA, was not included due to lack of data. Concomitant medications were defined as therapy with at least 1 day overlap with Apa and Enza. The top concomitant medications covering 99% of Apa and Enza population were assessed for pDDI using Micromedex, Lexicomp, and Drugs.com compendia. Results: We identified 149 Apa and 319 Enza patients with mean age 77 years across groups. The study population was primarily white (56.3% Apa; 56.7% Enza) and had Medicare insurance (81.0% Apa; 82.2% Enza). Mean Charlson comorbidity index scores were similar for each group (Apa: 2.3 [SD: 4.1]; Enza: 2.4 [SD: 2.4]). Polypharmacy was common in both groups, with the majority taking ≥5 medications (Apa: 79.8%; Enza: 75.9%). Of the co-medications included in this analysis, Micromedex, Lexicomp and Drugs.com flagged 12, 38 and 53 pDDIs for Apa, and 7, 35 and 49 pDDIs for Enza, respectively. A pDDI was identified for 35% Apa and 21% Enza patients using Micromedex and >80% of Apa and Enza patients using other compendia. The pDDIs by severity and risk rating as defined by the respective compendia are shown in Table. Specifically, 4 interactions for Apa and 1 for Enza were rated X (i.e., avoid combination). Conclusions: This study finds a high prevalence of pDDIs among Apa and Enza patients signifying the need for strict monitoring while initiating these therapies. Given the high prevalence of polypharmacy and comorbidities among nmCRPC, these patients may benefit from drugs with lower interaction potential. Future real-world analyses should be conducted to characterize the clinical and economic impact of these pDDIs as well as to assess pDDI for darolutamide. [Table: see text]
COVID-19 and hematologic diseases: Risk factors and long-term follow-up of CHRONOS19 Registry.
Authors: Zakurdaeva Kristina , Gavrilina Olga A. , Vasileva Anastasia N. , Dubov Sergei , Dubov Vitaly S. , Butaev Lev S. , Sukhareva Alena M. , Gavrilova Lubov V. , Toropova Inessa Yu. , Popova Marina O. , Siniaev Aleksandr A. , Kaplanov Kamil D. , Petrenko Andrei A. , Ochirova Oksana I. , Chelysheva Ekaterina , Chabaeva Yulia A. , Sveshnikova Yulia V. , Kunst Mikhail A. , Rakhmani Anzhelika F. , Savchenko Valery G.
Published: June 2021

e18715

Background: Pts with hem diseases are at high risk of COVID-19 severe course and mortality. Emerging data on risk factors and outcomes in this patient population is of great value for developing strategies of medical care. Methods: CHRONOS19 is an ongoing nationwide observational cohort study of adult (≥18 y) pts with hem disease (both malignant and non-malignant) and lab-confirmed or suspected (clinical symptoms and/or CT) COVID-19. Primary objective was to evaluate treatment outcomes. Primary endpoint was 30-day all-cause mortality. Long-term follow-up was performed at 90 and 180 days. Data from 14 centers was collected on a web platform and managed in a deidentified manner. Results: As of data cutoff on January 27, 2021, 575 pts were included in the registry, 486 of them eligible for primary endpoint assessment, n(%): M/F 243(50%)/243(50%), median age 56 [18-90], malignant disease in 452(93%) pts, induction phase/R/R/remission 160(33%)/120(25%)/206(42%). MTA in 93(19%) pts, 158(33%) were transfusion dependent, comorbidities in 278(57%) pts. Complications in 335(69%) pts: pneumonia (67%), CRS (8%), ARDS (7%), sepsis (6%). One-third of pts had severe COVID-19, 25% were admitted to ICU, 20% required mechanical ventilation. All-cause mortality at 30 days – 17%; 80% due to COVID-19 complications. At 90 days, there were 14 new deaths: 6 (43%) due to hem disease progression. Risk factors significantly associated with OS are listed in Tab 1. In multivariate analysis – ICU+mechanical ventilation, HR, 53.3 (29.1-97.8). Acute leukemias were associated with higher risk of death, HR, 2.40 (1.28-4.51), less aggressive diseases (CML, CLL, MM, non-malignant) – with lower risk of death, HR, 0.54 (0.37-0.80). No association between time of COVID-19 diagnosis (Apr-Aug vs. Sep-Jan) and risk of death. COVID-19 affected treatment of hem disease in 65% of pts, 58% experienced treatment delay for a median of 4[1-10] weeks. Relapse rate on Day 30 and 90 – 4%, disease progression on Day 90 detected in 13(7%) pts; 180-day data was not mature at the time of analysis. Several cases of COVID-19 re-infection were described. Conclusions: Thirty-day all-cause mortality in pts with hem disease was higher than in general population with COVID-19. Longer-term follow-up (180 days) for hem disease outcomes and OS will be presented. [Table: see text]
Mental health needs among parents of children with cancer: A commercial claims data analysis.
Authors: Hu Xin , Gilleland Marchak Jordan , Ji Xu
Published: June 2021

e18722

Background: Caring for a child diagnosed with cancer may adversely affect mental health (MH) of parents. However, little is known about MH care needs among parents of pediatric cancer patients. This study examined the patterns of MH care for parents of children diagnosed with cancer, as compared to parents of children without cancer. Methods: We used MarketScan® Commercial Database to identify continuously-insured parents of children receiving therapy for leukemia, lymphoma, central nervous system, bone, or gonadal cancers (aged ≤21 years at diagnosis) in 2009-2017. We also identified parents who matched eligibility criteria but had no child with cancer (with a randomly-assigned, fictitious date of cancer diagnosis) as controls. Outcomes included parents’ visits related to a MH disorder (anxiety, depression, substance use disorder [SUD], post-traumatic stress disorder [PTSD]) during six months before to 12 months after their child’s cancer diagnosis. Multivariable regressions were estimated to compare MH visits between 9,870 parents of pediatric cancer patients and 3,396,097 parents in the control group, adjusting for sociodemographic factors (parents’ age and sex, rurality, region, number of children in household) and presence of MH history. Among parents of pediatric cancer patients, we explored sociodemographic factors, MH history, and clinical factors (children’s cancer types, age at diagnosis, therapeutic modalities) associated with MH-related visits in multivariable regression analyses. Results: While the likelihood of MH history was similar between the two groups, a higher proportion of parents caring for cancer patients than controls had any visits related to anxiety (13.1%% vs. 9.5%), depression (9.6% vs. 7.5%), PTSD (0.5% vs. 0.4%), or any MH disorders (22.0% vs. 17.6%). These differences persisted in adjusted analyses. For example, parents of cancer patients were 24%, 37%, and 27% ( p-values < 0.001) more likely than controls to have any MH visits, anxiety-related visits, and depression-related visits, respectively. No difference was observed in SUD-related visits. Among MH care utilizers, no significant difference was observed in the number of MH visits. Among parents of cancer patients, those with MH history, mothers (vs. fathers), and parents of children with bone cancer (vs. leukemia) were more likely to have any MH visits ( p-values < 0.05). Parents whose children received surgery only and those with ≥3 children in household were less likely to have any MH visits ( p-values < 0.05). Conclusions: Parents of pediatric cancer patients have significantly higher needs for MH care as compared to the general parent population. Our finding underlines the importance of future interventions toward targeted MH counseling and supportive strategies for vulnerable parent groups, such as mothers and those caring for children undergoing more complex treatment plans.
ctDNA analysis in patients with cancer of unknown primary and its value in guiding targeted treatment when combined with predicted cancer types by 90-gene reverse-transcription polymerase chain reaction assay.
Authors: Liu Xin , Jiang Shiyu , Zhang Xiaowei , Zhou Xiaoyan , Luo Zhiguo , Hu Xichun
Published: June 2021

e18730

Background: No targeted agents except for drugs against NTRK fusion, dMMR/MSI-H or TMB-H are recommended for the treatment of cancer of unknown primary (CUP), despite of the occurrence of multiple actionable mutations identified by NGS. We aimed to explore the characteristics of circulating tumor DNA (ctDNA) and its value in guiding targeted treatment in combination with predicted cancer types by 90-gene reverse-transcription polymerase chain reaction assay for tissue origin. Methods: 172 treatment-naïve CUP patients with ctDNA testing were retrospectively included between April 2017 and Oct 2020. Of them, 98 patients had primary site predicted. Genetic alterations were reclassified based on their predicted primary site and the oncoKB scale. 153 patients treated with the first-line therapy and available survival data were used to explore prognostic value of detected genetic alterations in ctDNA. Results: We identified 82.6% (142/172) of patients had alterations detected, with the most commonly seen mutations of TP53 (51%), ARID1A (11%), KRAS (10%), RB1 (9%), APC (8%), PI3KCA (8%) and NFE2L2 (7%). The most commonly observed actionable mutations were PIK3CA (n=14, 9.8%), ERBB2 (n=7, 4.9%), BRAF (n=6, 4.2%), MET (n=6, 4.2%) and EGFR (n=5, 3.5%). After introducing predicted primary site in the 98 patients, 6.1% (n=6) of patients upgraded to a Level 1 alteration, 1.0% (n=1) to a Level 2 alteration (Table). In these 7 patients, only one patient with predicted lung cancer and EGFR 19 del received gefitinib with partial response for 5+ months. In multivariate analysis, NFE2L2 (hazard ratio [HR] = 2.96, 95%CI=1.32-6.61, P = .008) and CDKN2A mutation (HR = 2.50, 95%CI=1.26-4.96, P = .009) were independently associated with shorter PFS. Furthermore, NFE2L2 (HR = 4.96, 95%CI=1.98-12.43, P ＜ .001) and CDKN2A mutation (HR = 4.84, 95%CI=1.63-14.40, P = .005) were correlated with worse OS. Conclusions: This is the first attempt to integrate ctDNA sequencing and gene expression profiling for tissue of origin in OncoKB classification schema, resulting in 7.1% (7/98) of the genetic alterations reclassified to level 1 or 2, which might identify patients benefiting from corresponding targeted treatment. NFE2L2 and CDKN2A mutations in ctDNA were associated poor prognosis.[Table: see text]
Barriers to next-generation sequencing despite increased utilization: U.S. physician survey results.
Authors: Kaminski Allysen , Szamreta Elizabeth A. , Shah Ruchit , Ning Ning , Aggarwal Jyoti , Hussain Arif , Adeboyeje Gboyega
Published: June 2021

e18754

Background: The value of using next-generation sequencing (NGS) to inform oncology care decisions is increasingly apparent, yet many challenges persist that may inhibit routine adoption of NGS into clinical care. The purpose of this study was to identify existing barriers to NGS access and possible solutions from the physician perspective. Methods: A cross-sectional online survey, including both closed- and open-ended questions, was sent to a nationally representative sample of oncologists/hematologists, surgeons, and pathologists (N=201). The survey gathered information on physician demographics, practice characteristics, perceived barriers to testing, and strategies for increasing adoption. Results: Over 99% of physicians, 20.5% of whom worked in an academic setting, reported using NGS in the past 12 months, and 73.0% used NGS always or most of the time. Despite this high utilization, 80.1% of physicians experienced at least one barrier to testing. Reimbursement challenges were among the top reported barriers (87.5%), followed by a lack of knowledge of NGS testing methodologies (81.0%), and lacking evidence of clinical utility (80.1%). These barriers were more likely to be reported by pathologists and surgeons compared to oncologists/hematologists. Potential strategies for addressing these differed by specialty: While most oncologists/hematologists (84.0%) reported increased NGS coverage as a top priority, most surgeons (88.0%) prioritized improved multidisciplinary communications, and most pathologists (84.4%) prioritized increased access to educational content on cancer genomics and resources for physicians. Conclusions: Despite the high utilization of NGS among the surveyed stakeholders, several barriers, including limited reimbursement, knowledge gaps, and lack of clinical utility evidence were reported that may impact clinical optimization. Interestingly, the perceived barriers to NGS use varied by specialty, which may be driven by the differing roles these specialists play in patient management. Oncologists/hematologists, who are more likely involved in long-term patient care, were most concerned with identifying strategies to improve coverage of technology, whereas surgeons and pathologists were most concerned with strategies that would improve understanding and education. This research highlights the need for multi-faceted strategies to address barriers to NGS adoption. [Table: see text]
Survey study of barriers to evidence-based decision-making in oncology care using next-generation sequencing.
Authors: Szamreta Elizabeth A. , Kaminski Allysen , Shah Ruchit , Ning Ning , Aggarwal Jyoti , Hussain Arif , Adeboyeje Gboyega
Published: June 2021

e18757

Background: Next-generation sequencing (NGS) has the potential to accelerate precision medicine in oncology by informing efficient and improved clinical treatment decision-making. However, discussions on the utility of NGS in clinical practice are ongoing. This survey study examined clinical utility barriers to adoption of NGS into oncologic care. Methods: A cross-sectional online survey was sent to a nationally representative sample of oncologists/hematologists, surgeons, and pathologists (N=201). The survey gathered information on physician demographics, practice characteristics, perceived barriers to NGS testing, and potential strategies for increasing adoption. Results: Almost all physicians in the sample (99.5%) reported using NGS. Physicians reported the following aspects of NGS as the most valuable: ability to guide decision-making (73.1%), more accurate identification of corresponding treatment (56.7%), comprehensive genomic coverage (54.2%), efficient technology with faster turnaround time (49.8%), and more accurate diagnosis or prognosis (41.3%). Physicians reported that NGS results guided treatment decisions for 63% of patients (Range: 2% - 100%). Over 85% of physicians reported that confidence in interpreting results and availability of clinical guidelines were important in undertaking NGS. Correspondingly, limited evidence of clinical utility was a top barrier to testing (80.1%), with pathologists and surgeons more likely than oncologists/hematologists to consider this. Overall, 76% of physicians shared that strategies to alleviate these clinical utility barriers included increased evidence, standardized guidelines, and interpretation support. Conclusions: Given the high uptake of NGS testing in this physician sample, but the lower rates of application of test results to guide treatment, the clinical impact of NGS may not be fully optimized. This discrepancy highlights the ongoing need for real-world evidence to better understand and further optimize the evolving role of NGS in the context of the overall management of the cancer patient. [Table: see text]
Real-world risk of anosmia with cancer directed systemic therapy: A pharmacovigilance assessment using FDA Adverse Events Reporting System (FAERS) database.
Authors: Kaur Anahat , Wang Shuai , Yu Arlene , Elrafei Tarek N. , Steinberg Lewis , Kumar Abhishek
Published: June 2021

e18790

Background: Anosmia is a rare and under-reported adverse event associated with the use of several oncologic drugs. Instances of olfactory disturbances following administration of chemotherapeutic agents have been sporadically documented in case reports and case series. We aimed to conduct a more comprehensive study to generate signal for anosmia as adverse effect of drugs used for oncologic indications. Methods: The United States Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) database, a pharmacovigilance database, was used to extract data. All reported cases of anosmia in the database were filtered for an indication of cancer. Descriptive analysis was conducted using SPSS 26. Results: Total 10250 cases of anosmia were extracted from FAERS database. Out of these, cancer as an indication for medication use was noted in 139 cases. Some of the most common suspect medications exclusively associated with more than one case of anosmia were palbociclib (n=16), enzalutamide (13), pazopanib (8), cabozantinib (8), letrozole (6), leuprolide (5), niraparib (5), rucaparib (4), tamoxifen (4), capecitabine (3), everolimus (3), anastrazole (2), exemestane (2), zoledronic acid (2), vandetanib (2) and vismodegib (2). Detailed description of medications with highest number of reported cases is listed in Table. Median age at diagnosis was 66 years (interquartile range 58-71). Anosmia was reported more commonly in females (64% ) as compared to males (33.8%). Reactions were reported to the FDA more commonly by consumers (56.8%) as compared to healthcare professionals (40.3% cases). Out of 139 patients with anosmia, 93 (66.9%) had concomitant ageusia, 8 (5.7 %) had dysgeusia and 6 (4.3%) patients had neuropathy. Conclusions: This study demonstrates a signal for anosmia as side effect in patients receiving select oncologic medications based on the FAERS database. It is worth noting that none of the suspect medications identified in this study have anosmia listed as known adverse reaction on accompanying package insert. Further studies need to be conducted to confirm if causal relationship exists between use of these drugs and olfactory function compromise. [Table: see text]
Cost-effectiveness of atezolizumab and bevacizumab in advanced hepatocellular carcinoma.
Authors: Patel Kishan , Stein Stacey , Luther Janki , Huntington Scott F.
Published: June 2021

e18829

Background: The IMbrave150 trial found that atezolizumab and bevacizumab significantly prolonged progression-free survival (PFS) and overall survival (OS) in patients with locally advanced metastatic or unresectable hepatocellular carcinoma (HCC), compared to sorafenib. However, atezolizumab and bevacizumab are costly treatments and are administered indefinitely until disease progression. Therefore, it is unclear whether atezolizumab-bevacizumab is cost-effective in this clinical setting. Methods: We constructed a partitioned survival model to compare the costs and effectiveness of atezolizumab-bevacizumab to sorafenib in advanced HCC. PFS and OS curves for each treatment strategy were derived from the IMbrave150 trial using parametric survival modeling. The utility of each health state and the costs of treatment, adverse events, and terminal care were derived from literature and Medicare fee schedules. We calculated the incremental cost-effectiveness ratio (ICER) of atezolizumab-bevacizumab from a US healthcare perspective, using a lifetime horizon, an annual discount rate of 3%, and a willingness-to-pay threshold of $150,000/quality-adjusted life year (QALY). One-way and probabilistic sensitivity analyses were performed to evaluate the robustness of model conclusions. Results: Atezolizumab-bevacizumab was associated with an incremental cost of $102,648 and an incremental effectiveness of 0.42 QALYs compared to sorafenib, leading to an ICER of $244,213/QALY (Table). The price of atezolizumab would need to be reduced by 40% (from ̃$9,400 to ̃$5,700 per dose) or the price of bevacizumab would need to be reduced by 47% (from ̃$8,400 to ̃$4,400 per dose) for atezolizumab-bevacizumab to be cost-effective compared to sorafenib. Alternatively, the price of both atezolizumab and bevacizumab would need to be simultaneously decreased by ̃21% for the combination therapy to be cost-effective. Our model was most sensitive to the hazard ratios (HR) of OS and PFS; varying the HRs across the 95% confidence interval reported in IMbrave150 (0.42-0.79) corresponded to ICERs of $137,435/QALY and $621,365/QALY, respectively. During probabilistic sensitivity analyses, >99%, 99%, and 90% of iterations produced ICERs greater than willingness-to-pay thresholds of $50,000/QALY, $100,000/QALY, and $150,000/QALY, respectively. Conclusions: Use of atezolizumab-bevacizumab for advanced HCC is unlikely to be cost-effective under current pricing. Significant price reduction of atezolizumab and/or bevacizumab would be required to reduce the ICER to a more widely acceptable value.[Table: see text]
Cost-efficiency analysis of conversion from reference pegfilgrastim to its biosimilar (pegfilgrastim-jmdb) and expanded access to food and transportation support for Medicare/Medicaid patients within the CMS Oncology Care Model.
Authors: MacDonald Karen , AlRawashdh Neda , McBride Ali , Abraham Ivo
Published: June 2021

e18837

Background: The CMS Oncology Care Model (OCM) aims to improve quality of care and health outcomes in cancer centers at the same or lower cost. We performed cost-efficiency analyses of converting selected cancer patients (pts) from reference pegfilgrastim (PFG) to its biosimilar (PFG-jmdb); and simulated re-allocating savings to provide nutrition and transportation support to CMS beneficiaries within OCM. Methods: Incidence rates for breast, ovarian, lung, colorectal cancers and non-Hodgkin lymphoma were extracted from SEER, further stratified by age <65 (commercial insurance) or >65 (Medicare) adjusted for Medicare/Medicaid mix. Chemotherapy (CTX) rates were matched to tumor type; of these 19.4% were assumed to require PFG prophylaxis (PPX). Two models compared respectively prefilled syringe (PFS) and on-body injector (OBI) reference PFG to PFS PFG-jmdb. Cost inputs included Average Sales Price (ASP) 3Q20 for Medicare and National Average Drug Acquisition Cost (NADAC, estimated by wholesale acquisition cost (WAC)-3.9%) for Medicaid pts plus medication administration. Cost savings across various biosimilar conversion rates for CTX cycles 1-6 were translated into $100 units of healthy food or medical transportation. Results: In 2020, biosimilar conversion for the estimated 31,210 Medicare and 1,722 Medicaid pts in the 5 tumor types needing PFG PPX yielded savings of up to ̃$19M (Medicare) and ̃$20M (Medicaid). These savings could have provided a monthly $100 food or transportation check to at least 24,716 Medicare or 33,630 Medicaid pts for 6 months. Conclusions: Savings from biosimilar conversion can be re-allocated on a budget neutral basis to food and transportation support to pts with such needs. This achieves the dual OCM aim of reducing drug budgets while enhancing patient-centric support services.[Table: see text]
Cost-effectiveness of atezolizumab monotherapy versus pembrolizumab monotherapy for first-line (1L) treatment of metastatic non-small cell lung cancer (mNSCLC).
Authors: Lin Chia-Wei , Rosettie Katherine , Bilir Pinar , Celik Hazal , Abogunrin Seye , Ogale Sarika
Published: June 2021

e18847

Background: Atezolizumab monotherapy is indicated as 1L treatment for mNSCLC patients with high programmed death ligand-1 (PD-L1) expression (≥ 50%) and without epidermal growth factor receptor or anaplastic lymphoma kinase mutations. This analysis assessed the cost-effectiveness of 1L atezolizumab monotherapy vs. pembrolizumab monotherapy for mNSCLC patients with high PD-L1 expression from a US third-party payer perspective. Methods: A Markov model with progression-free, progressive disease (PD), and death states was developed in Microsoft Excel to compare clinical and cost outcomes of atezolizumab monotherapy vs. pembrolizumab monotherapy. Efficacy, safety, and utility data were derived from systematic reviews and indirect comparisons of the IMpower110, Keynote-024, and Keynote-042 trials. Product prescribing information and clinical trials informed dosing and administration. Wholesale acquisition cost (WAC, accessed in January 2021) for drugs were used while other cost inputs were derived from publicly available fee schedules and peer-reviewed literature. The key outcome of interest was the incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained. Deterministic sensitivity analysis with 20% variation and probabilistic sensitivity analyses (PSA) were performed to address uncertainties around input parameters. Results: In the base case, 1L atezolizumab monotherapy was projected to increase life expectancy for patients by 0.60 life-years (4.35 vs. 3.75) and 0.47 QALYs (3.46 vs. 2.98) over pembrolizumab monotherapy at an incremental cost of $27,947 (mean total cost: $396,811 vs. $368,864), resulting in an ICER of $58,841/QALY gained. Results of the deterministic sensitivity analysis were most sensitive to changes in discount rates for costs and care costs in the PD state. The PSA showed that the probability of atezolizumab being cost-effective at willingness-to-pay thresholds of $100,000 and $150,000 was 41% and 49%, respectively. Conclusions: First-line atezolizumab monotherapy had 0.6 life-years and 0.47 QALYs gained compared with pembrolizumab monotherapy and was estimated to be cost-effective (ICER $58,841/QALY). As the ICER falls below the US cost-effectiveness thresholds ( < $100,000-$150,000/QALY), clinicians and payers should consider atezolizumab monotherapy as a cost-effective 1L option for mNSCLC patients with high PD-L1 expression.
Response rates in acute myeloid leukemia patients treated with attenuated durations of venetoclax in combination with hypomethylating agents.
Authors: Blanding Dena , Jonathan Bakos Keegan , Rangel Christopher Andrew , Pasyar Sarah , Hill Elizabeth Goodwin , Davis James , Hess Brian T. , Baratam Praneeth , Greenwell Irl Brian
Published: June 2021

e19008

Background: The combination of the Bcl-2 inhibitor, venetoclax, with hypomethylating agents (HMA) recently emerged as an efficacious treatment for older adults with acute myeloid leukemia (AML) who are not eligible for intensive induction therapy. In a phase III randomized controlled trial of HMA +/- venetoclax, DiNardo et al demonstrated impressive composite complete response rate and complete response with incomplete recovery (CR+CRi) of 66% in the venetoclax arm as compared to 28% in the placebo arm. Despite HMA/Venetoclax being lower intensity, 83% of patients developed grade 3 hematologic adverse events, and 42% of patients experienced febrile neutropenia in the venetoclax arm, as compared to 19% in the placebo arm. In the trial, venetoclax was given continually for 28 day cycles, with some patients receiving shortened durations of venetoclax (21 days) due to toxicity. To reduce toxicity, some institutions have further limited the duration of venetoclax in cycle 1. Here, we report response rates with attenuated durations of venetoclax with HMA. Methods: We conducted a retrospective study of AML patients who received venetoclax in combination with HMA, excluding those with prior chemotherapy for AML or MDS, or previous exposure to HMA or venetoclax. Demographic, cytogenetic, pathology, and outcome data were collected including bone marrow biopsy results at diagnosis and after cycle 1 (day +28) or cycle 2 (day +56). The primary outcome was composite response rate (CR+CRi) following cycle 1 or cycle 2 defined by 2017 ELN criteria. Results: 25 patients were identified with median age of 73 (range 63-82). 9 patients received 14 or less days of venetoclax (attenuated duration): < 8 days in 1 patient and 8-14 days in 8 patients. 16 patients received 21 days or more (standard duration): 21 days in 14 patients, and 28 days in 2 patients. Of the patients who received an attenuated duration, the median age was 74 (68-82), 22% had either a TP53 mutation or deletion, 56% had complex karyotype, and 44% had received prior cytotoxic chemotherapy. Of the patients who received standard duration therapy, the median age was 71 (63-81), 44% had either a TP53 mutation or deletion, 75% had complex karyotype, and 6% had received prior cytotoxic chemotherapy. The composite response rate was 78% in the attenuated duration group and 75% in the standard duration group (p > 0.99). Conclusions: Though a limited sample size, this data suggests high response rates can be observed with attenuated courses of venetoclax. With appropriately selected patients, the feasibility of attenuated venetoclax courses could be further explored in larger prospective studies.[Table: see text]
Associations of coping strategies with quality of life (QOL) and mood in patients with acute myeloid leukemia (AML).
Authors: Reynolds Matthew J. , Lavoie Mitchell W. , Jones Bailey T. , Nelson Ashley M. , Amonoo Hermioni L. , LeBlanc Thomas William , El-Jawahri Areej
Published: June 2021

e19012

Background: Patients with AML who receive intensive chemotherapy experience immense physical and psychological symptoms, which can result in a substantial deterioration of QOL. As data on the relationship between AML patient coping strategies and patient-reported outcomes are lacking, we aimed to determine the associations between patients’ coping strategies and their quality of life and mood. Methods: We conducted a secondary analysis of cross-sectional data from a multi-site randomized supportive care trial for hospitalized patients diagnosed with AML and receiving intensive chemotherapy. Within 72 hours of initiating chemotherapy, patients completed baseline assessments of QOL (FACT-Leu), anxiety and depression symptoms (HADS), and symptom burden (ESAS). Patients also completed subscales from the Brief Cope to assess baseline use of coping strategies. We created high-order factors (approach-oriented coping vs. avoidant-oriented coping) from the coping subscales and utilized the median split method to identify the proportions of patients with high use of approach and avoidant-oriented coping strategies, respectively. We used linear regression models adjusting for age, gender and diagnosis type (newly diagnosed vs. relapsed/refractory AML) to examine the relationships between patients’ use of coping strategies and their baseline QOL, mood and symptom burden. Results: A total of 160 patients were enrolled in the study (60.0% male; median age 64.4 years [range 19.7-80.1]). Overall, 47.5% (76/160) of patients reported high use of approach-oriented coping strategies, while 38.8% (62/160) reported high use of avoidant-oriented strategies. In regression models, the greater use of approach-oriented coping strategies at baseline was associated with higher baseline QOL (β = 1.33, SE = 0.44, P= 0.003), lower depression (β = -0.28, SE = 0.07, P< 0.001) and anxiety symptoms (β = -0.24, SE = 0.08, P= 0.002), and lower symptom burden (β = -0.96, SE = 0.34, P= 0.006). By contrast, the greater use of avoidant-oriented coping strategies at baseline was associated with lower baseline QOL (β = -4.98, SE = 0.81, P< 0.001), higher depression (β = 0.60, SE = 0.13, P< 0.001) and anxiety symptoms (β = 0.79, SE = 0.14, P< 0.001), and worse symptom burden (β = 2.30, SE = 0.64, P< 0.001). Conclusions: Newly hospitalized patients with AML who utilize approach-oriented coping strategies experience better baseline QOL and mood, and a lower symptom burden. These findings underscore the need for supportive care interventions that promote effective coping in patients with AML, to improve patients’ QOL and reduce their physical and psychological distress.
Low incidence of hepatic veno-occlusive disease (VOD) in patients with B-cell acute lymphoblastic leukemia (B-ALL) treated with inotuzumab ozogamicin (INO) followed by allogeneic stem cell transplantation (allo-SCT).
Authors: Cahill Kirk , Alban Juan , Mortel Mylove , Dworkin Emily , Kosuri Satyajit , Duvall Adam , Liu Hongtao , Bishop Michael Russell , Larson Richard A. , Stock Wendy
Published: June 2021

e19024

Background: Hepatic VOD is an uncommon, but often fatal complication of allo-SCT. The risk is increased after INO, an anti-CD22 antibody conjugated to calicheamicin with high remission rates in relapsed CD22-positive B-ALL. Previous reports have described VOD rates as high as 19% in INO-treated patients who then received allo-SCT. We report our safety experience using INO followed by allo-SCT. Methods: We identified patients >18 yrs with B-ALL treated with allo-SCT and INO in the University of Chicago IRB-approved SCT database. We reviewed the EMR for patient details, toxicities (CTCAE v5.0), and outcomes. Hepatic VOD was defined according to EBMT criteria. Overall survival (OS) was from time of allo-SCT to death or last follow-up. Results: Between 2010-2021, 72 adult patients with B-ALL received allo-SCT, and 17 also received INO as salvage therapy (Table). Median follow-up was 19 months (1-110). All received ursodiol prophylaxis and 15/17 received an azole for antifungal prophylaxis. They had median 2 cycles (1-3) of INO with median of 1.9 months (1-14) from the last dose of INO to allo-SCT. For cycle 1, 13/17 (77%) received 0.8 mg/m2 on D1 and 0.5 mg/m2 on D8 and D15. Of these, 11 had a subsequent cycle (5 with same dosing and 7 had 0.5 mg/m2 on D1, D8, and D15). 1 patient had 0.5 mg/m2 on D1, D8, and D15 for 2 cycles. 3 patients received 0.8 mg/m2 on D1 and 0.4 mg/m2 on D8 and D15 for 2 cycles. After INO, 10 patients achieved CR and 3 had CRi for ORR of 13/17 (76%). The 4 patients with persistent disease despite INO went into remission with a different salvage therapy prior to allo-SCT. Conditioning regimens are listed in Table 1. No patients developed VOD after allo-SCT. Within 2 yrs of allo-SCT, 3/17 (18%) relapsed and 7/17 (41%) died. The median OS was 21.2 months [18 - NR]. Conclusions: Limiting the number of INO cycles (median 2) prior to allo-SCT, delaying allo-SCT for 2 months after INO exposure, and avoiding dual alkylating agent conditioning may have contributed to the absence of VOD in our patients. Larger data sets will be useful to validate these important safety observations.[Table: see text]
Outcomes and predictors of hospital mortality of patients with Philadelphia-negative myeloproliferative neoplasms and sepsis: A Nationwide Inpatient Sample Database analysis.
Authors: Gonzalez Mosquera Luis F. , Tobar Pool , Cardenas Maldonado Diana D. , Moscoso Bernard , Podrumar Alida I. , Cuenca John A.
Published: June 2021

e19038

Background: Sepsis is associated with increased mortality in patients with hematologic malignancies, especially in those receiving cytotoxic chemotherapy. The development of new therapies also increases the risk of infections in Philadelphia negative myeloproliferative neoplasms (MPN). However, the clinical implications and costs of sepsis in patients with polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF) have not been reported at a national level. Therefore, we aimed to determine the outcomes, hospitalization costs, and predictors of mortality in patients with MPN and sepsis. Methods: We retrieved adult patients with MPN from the Nationwide Inpatient Sample database from 2016-2018. We used the ICD-10 codes to identify and compare patients with and without sepsis. The main outcomes were hospital mortality and predictors of mortality. We computed the chi-squared test and the Mann-Whitney U-test. Mortality predictors are estimated using multivariate logistic regression and logistic fixed-effect methods to control for admission cohort and hospital time invariant characteristics. All analyses were performed using Stata Statistical Software version 14 (StataCorp, College Station, TX). Results: A total of 86,723 patients with MPN were identified. The majority of them were white (66.9%), female (54.3%), with a median age of 62 (IQR 47-76). The most common MPN was ET (84.3%), followed by PV (14.2%). Sepsis was diagnosed in 16,146 (18.6%) of the MPN patients. There was a significantly higher mortality in the sepsis group vs. the non-sepsis group (7.4% vs. 1.8%; p < 0.001), longer LOS (8 vs. 4 days; p < 0.001), and higher median hospitalization cost (US$74,128 vs. US$39,987; p < 0.001). In the multivariable analysis, sepsis was associated with higher mortality (OR: 4.74; CI 95%: 4.33-5.18; p < 0.001). Among the MPN, those with PMF and sepsis had a higher risk of death (OR: 2.21; CI 95%: 1.72-2.82; p < 0.001). Other significant variables associated with mortality were age > 65 (OR: 2.51; CI 95%: 2.14-2.95; p < 0.001), concomitant chronic heart failure (CHF) (OR: 1.57; CI 95%: 1.39-1.77; p < 0.001), chronic kidney disease (CKD) (OR: 1.22; CI 95%: 1.10-1.35; p < 0.001), and weight loss (OR: 2.12; CI 95%: 1.79-2.51; p < 0.001). There was no significant association with sex and race/ethinicity. Conclusions: On patients with MPN, sepsis was associated with higher mortality, hospitalization costs, and LOS. Additionally, those with increased age, CHF, CKD, weight loss, and PMF were also at increased risk of death. There should be more emphasis on assessing the risk of sepsis on MPN to prevent worse outcomes and higher costs. Further studies should focus on identifying the specific causes of sepsis in MPN and promoting early recognition.
Outcomes of CNS involvement in blastic plasmacytoid dendritic cell neoplasm (BPDCN).
Authors: Greenwell Irl Brian , Davis James , Li Hong , Soong Deborah , Taylor Justin , Lane Andrew A. , Rizzieri David
Published: June 2021

e19043

Background: BPDCN is rare cancer commonly involving the skin and marrow. Tagraxofusp (Tag), a CD123 targeted therapy, was the first FDA approved drug for BPDCN in 2018. CNS involvement occurs in 10-60% of patients and CNS staging and prophylactic (ppx) practices are variable. The pivotal trial of Tag in BPDCN did not require CNS staging and excluded those patients with known CNS involvement. Here, we describe one of the largest cohorts of BPDCN patients with known CNS involvement, including patients treated with Tag. Methods: We collected data from 4 centers on patients with CNS involvement defined by LP or imaging with high clinical suspicion. Survival was estimated via the Kaplan-Meier method with other analyses being descriptive. Results: CNS involvement was identified in 11 patients. Median age was 74 (range 51–83) and 10 were male. 5 patients had CNS staging at initial diagnosis. At time of CNS involvement, 6/11 patients had neuro symptoms. Prior to diagnosis of CNS involvement, 5 received Tag and none received CNS ppx. Of 9 patients treated for their known CNS involvement (table), one received CNS directed systemic therapy, with all others being treated with intrathecal (IT) chemotherapy. All patients treated with 3 or more doses of IT chemotherapy cleared their CSF, and survived at least 6 months from the diagnosis of CNS involvement, including two patients (#5 and 8) with large burden CNS disease and neuro symptoms. Median survival from time of diagnosis of BPDCN was 13.8 months (2.7-35.5) and from time of diagnosis of CNS involvement was 6.0 months (0.1-25.7). Conclusions: Asymptomatic CNS involvement by BPDCN is common; routine staging and ppx should be considered at diagnosis. Tagraxofusp did not appear to prevent the development of CNS disease. IT therapy effectively cleared and controlled CNS involvement in a majority of patients. IT therapy may be sufficient to control CNS disease and IT prophylaxis should be considered, including in patients on CD123 targeting therapies. Our results provide new insights into BPDCN with CNS involvement and include patients treated with recently developed novel systemic therapies.[Table: see text]
Chimeric antigen receptor T-cell therapy real-world assessment of total cost of care and clinical events for the treatment of relapsed or refractory lymphoma.
Authors: Sahli Brett , Eckwright David , Darling Eric , Gleason Patrick P. , Leach Joseph W.
Published: June 2021

e19500

Background: Axicabtagene ciloleucel and tisagenlecleucel are FDA approved to treat relapsed or refractory B-cell lymphoma. CAR-T therapy involves a complex process of extraction, transfection, administration and management of adverse reactions such as cytokine release syndrome. Little has been established using real world evidence identifying CAR-T episode total cost of care (TCC) and post administration clinical events (CE) among the commercially insured population. Methods: Integrated pharmacy and medical claims were queried among a population of 15 million commercially insured members from Jan 2018 to June 2020 to identify members 18 years and older with a CAR-T drug claim cost of > $250,000, lymphoma dx, no leukemia dx, and continuously enrolled through a CAR-T episode of 30 days prior to and 56 days post the CAR-T administration date. The TCC and CAR-T specific costs were calculated for the episode. Inpatient (IP) days pursuant to CAR-T administration were calculated using admission and discharge dates. Post CAR-T administration date CEs defined as subsequent chemotherapy, bone marrow transplant (BMT), and death or hospice, as well as time to event (TTE) were identified. Subsequent chemotherapy post CAR-T administration was identified. Results: 74 members, 59% male and mean age 55 years (min 18, max 76), met inclusion criteria. Mean CAR-T episode TCC was $711,884 (median $610,999) with mean CAR-T drug cost $527,547 (median $411,278). Mean IP days per episode were 17.3 (standard deviation [SD]) 9.6). 29 members (39%) experienced any CE with a mean 228 (SD 217) TTE. No CE identified among 21 (28%) members who disenrolled or ceased claim activity after a mean 253 days (SD 167). 24 (32%) remained enrolled with no CEs with a mean follow-up of a 390 days (SD 264), as of Oct 2020. Non-mutually exclusive CEs include: 22 (30%) members received subsequent chemotherapy, mean TTE 263 days (SD 238); 4 (7%) had a BMT, mean TTE 245 days (SD 108); and 13 (18%) had an identified death or hospice, mean TTE 297 days (SD 143). The most common non-mutually exclusive subsequent chemotherapy observed in 22 members were: rituximab (9 members), bendamustine (8), lenalidomide (8), obinutuzumab (5), pembrolizumab (4), polatuzumab vedotin (4), cyclophosphamide (3), ibrutinib (2), and venetoclax (2). 14 additional subsequent therapies with 1 unique utilizer were also observed. Conclusions: These 74 members show substantial variation in CAR-T episode TCC and clinical experience. 29 (39%) members did not have a durable response to CAR-T with providers initiating subsequent chemotherapy in 22 of 29 cases in the absence of clear guidelines. These data inform managed care activities such as performance metrics, case rates, and value based arrangements. Additionally, these data are important in actuarial forecasting for given the potential future volume of treated patients and spend.
Clinical and morphological characteristics or immunohostochemical factors determine the results of treatment for diffuse large B-cell lymphoma?
Authors: Kushtova Luiza B. , Frantsiyants Elena M. , Bandovkina Valeria A. , Nikolaeva Nadezhda V. , Kapuza Elena A. , Kozel Yuliya Yu. , Kozyuk Olga V. , Dmitrieva Viktoria V.
Published: June 2021

e19539

Background: Diffuse large B-cell lymphoma (DLBCL) is and aggressive heterogeneous tumor. The treatment is ineffective in more than 30% cases: primary resistance is observed in 20%, and relapses in 10%. Clinical prognostic indices do not allow assessing the DLBCL course and treatment outcomes. The purpose of the study was to evaluate the results of treatment of DLBCL patients depending on clinical and immunohistochemical factors of the disease prognosis. Methods: Patients with DLBCL (n = 48): men – 25 (52.1%, mean age 52±3.8 years), women – 23 (47.9%, mean age 60±4.3 years) received standard treatment R-CHOP, R-CHOEP, R-EPOCH. Results: After the treatment, 27 (56.2%) patients were in remission for 3 years, 10 (20.8%) patients developed relapses, and 11 (23%) patients were refractory to the therapy. All groups demonstrated Ki-67 > 80%, overexpression of Bcl2, Bcl6, CD10, MUM-1 on tumor cells, C-MYC gene rearrangements. Patients with stage I and II nodal spread were more likely to be in remission; refractory patients and those with early relapses had stages III and IV. Relapses were detected at different periods after treatment: early relapses (n = 5) within 6 months and late relapses (n = 5) after 12 months or later. Among patients with early relapses, 2 (40%) had extranodal disease and 3 (60%) nodal disease; high/medium IPI was noted in 3 patients, low/medium and low IPI – 1 patient each. Among patients with late relapses, 3 patients had nodal disease and 2 – primary extranodal disease; high/medium IPI was noted in 2 patients, low/medium – in 3 patients. Among recurrent patients, 9 had non-germ cell DLBCL and 1 - germ cell DLBCL. Among refractory patients, 8 (73%) had nodal disease and 3 (27%) - extranodal disease; low/medium IPI was registered in 4 patients, high/medium IPI in 2, low IPI in 5 patients; germ cell tumors in 2 patients, non-germ cell tumors in 9 patients. Conclusions: 33% of DLBCL patients did not benefit from the treatment. Molecular markers such as Ki-67, Bcl2, Bcl6 and CD10 were not prognostically significant. The tumor type had a prognostic value only in the group of patients with relapses - non-germ cell tumors were found in 90% of cases.
Survival outcomes of post-transplant lymphoproliferative disorder: A 12-year analysis.
Authors: Shaikh Hira Ghazal , Khan Rafiullah , Grabel Michael , Jandarov Roman , Charif Mahmoud , Latif Tahir
Published: June 2021

e19543

Background: Post-transplant lymphoproliferative disorder (PTLD) is a rare and potentially fatal complication of chronic immunosuppression in solid organ transplant (SOT) and hematopoietic stem cell transplant recipients. With an overall incidence of ̃ 1 percent in the transplant recipients, it is the most common malignancy, with the exception of skin cancer, after SOT in adults. There is a paucity of information concerning the outcomes and prognostic indicators of PTLD. Methods: We queried the National Cancer Database (NCDB) from 2004 – 2015 for patients with diagnosis of PTLD. Overall survival (OS) was calculated from the date of diagnosis to the date of last contact or death using Kaplan Meier curves to present the cumulative probability of survival. Additionally, Poisson regression was used to test the association between baseline variables and days to event. All statistical analyses were performed using R 4.0.3. Results: Total number of patients identified by inclusion criteria was 425. 1-year OS was 73% (CI 0.684, 0.776), 3-year OS 63% (CI 0.581, 0.683), and 5-year OS 56% (CI 0.502, 0.619) in patients with survival data available (n = 365). 263 patients were excluded due to incomplete data, yielding a final cohort of 192 patients for correlational analysis. The median age was 59 years. Majority were males (60%), < 65 year old (75.5%), Hispanics (91%), and had Charlson-Deyo Comorbidity score of 0 (63.5%). 77% were Caucasians while 15.6% were African Americans. OS was longer in males, Caucasians, patients who received radiation (versus no radiation), those treated at academic or comprehensive cancer center (versus community cancer center), had annual income > $63000 (versus < $63000) by Poisson regression analysis, however the difference was not statistically significant. Conclusions: Our data demonstrates a trend toward poor survival with socioeconomic and treatment variables including gender, race, annual income, treatment center expertise and radiation treatment. Randomized trials are needed to further assess the outcomes of PTLD.