bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of new-onset hypertension in patients (pts) with newly diagnosed chronic lymphocytic leukemia (CLL) treated with Bruton tyrosine kinase inhibitors (BTKi): A real-world data study using the Symphony Health Solution database.
Authors: Kou Tzuyung Douglas , Zhou Lili , Zhou Jinzhi , Cohen Aileen , Aldairy Wassim , White William B 
Published: June 2024

e19014 Background: BTKis provide an important therapeutic option for pts diagnosed with CLL. Concerns have arisen about a potential association with the risk of cardiovascular events with BTKi. Using the Symphony Health Solutions database, this study describes the risk of new-onset hypertension in CLL pts treated with and without BTKis. Methods: Newly diagnosed CLL pts who started ibrutinib or acalabrutinib and those not treated with an approved BTKi between 2019 and 2022 were included in the analysis. The prevalence of hypertension prior to and risk of new-onset hypertension after treatment initiation were defined by use of antihypertensive medication. Pt demographics and comorbidities were described. Multivariate regression and inverse probability treatment weight based on propensity score were used to account for bias due to differences in pt characteristics between groups. Results: In CLL pts treated with (n=7,114) and without BTKis (n=34,571), demographics and clinical characteristics included age at the index date (mean: 70.2 yrs, BTKi; 69.0 yrs, without BTKi), sex (male: 59.8%, BTKi; 55.7%, without BTKi), and Charlson comorbidity scores (mean: 3.3, BTKi; 3.1, without BTKi). At baseline, the prevalence of hypertension defined by the use of antihypertensive medication was 67.8% with BTKi and 67.6% without BTKi. Among pts without any antihypertensive medication use at baseline, the rates of new-onset hypertension within 1 yr after treatment initiation were greater in pts with BTKis than without BTKis (Table). Conclusions: In this real-world analysis, CLL pts treated with BTKis had a higher burden of comorbidities, and use of antihypertensive medication was common. The risk of new-onset hypertension was higher in pts initiated on BTKis than those on non-BTKi treatments. These data suggest that development of hypertension is an important consideration in the long-term management of CLL pts undergoing BTKi treatment. [Table: see text]
Incidence of any infections and SARS-CoV-2 infections in patients receiving treatment for follicular lymphoma and diffuse large B-cell lymphoma: Real-world evidence from a large US national claims database.
Authors: Omofuma Omonefe O. , Breskin Alexander , Shao Ping , Asubonteng Julius , Archambault Alexi N. , Hampp Christian , Shariff Saleem , Hearnden Claire , Ambati Srikanth R. , Mohamed Hesham 
Published: June 2024

e19061 Background: Non-Hodgkin’s lymphoma is a heterogeneous group of conditions, including the indolent subtype follicular lymphoma (FL) and the aggressive subtype diffuse large B-cell lymphoma (DLBCL). Infections associated with NHL are a major concern due to effects of the underlying disease and its treatment and have been reported to increase with increasing lines of therapy (LoT). However, the risk of infections overall and SARS-COV-2 infections specifically is not well characterized in patients who have received multiple LoTs. The goal of the study was to estimate the exposure-adjusted incidence rates (EAIR) of infections during the COVID-19 pandemic by type, severity and LoT received in patients treated for FL or DLBCL in the real-world setting. Methods: We identified patients in the Optum Clinformatics claims data from October 1, 2015, to June 30, 2023. Patients were aged ≥18 years, enrolled continuously for 365 days before index (start of LoT), and had ≥2 ICD-10 diagnosis codes for FL or DLBCL in the 365 days before index. The EAIR (per 100 person-years, PY) was estimated for infections by type (any infections and SARS-COV-2 [after 1/1/2020]), severity (hospitalized or fatal hospitalizations), and number of LoTs received. Results: A total of 4,799, 989 and 249 FL patients were included in the 1L (1 LoT), 2L, and 3L+ cohorts, respectively. The EAIR of infections resulting in hospitalization in 1L, 2L, and 3L+ cohorts were 20.4 (95% confidence interval (CI): 18.9-22.1), 32.5 (27.4-38.5), and 56.7 (44.3-72.5) per 100-PY for any infection; and 9.7 (8.1-11.5), 8.5 (4.4-13.4) and 11.6 (6.2-21.5) per 100-PY for SARS-COV-2 infections, respectively. The EAIR of fatal hospitalizations were 4.1 (3.5-4.8), 9.3 (7.0-12.4), and 14.9 (9.8-22.8) per 100-PY for any infection; and 2.7 (2.0-3.8), 3.1 (1.5-6.5), and 3.1 (1.1-10.5) per 100-PY for SARS-COV-2 infections. A total of 8,058, 2,114 and 682 DLBCL patients were included in 1L, 2L, and 3L+ cohorts, respectively. The EAIR of infections resulting in hospitalization in 1L, 2L, and 3L+ cohorts were 64.2 (60.7-67.8), 85.2 (76.9-94.3), and 113.4 (98.4-130.7) per 100-PY for any infection; and 13.1 (11.4-15.1), 14.4 (10.9-19.0), and 22.8 (16.7-31.0) per 100-PY for SARS-COV-2 infections respectively. The EAIR of fatal hospitalizations were 12.0 (10.8-13.3), 23.0 (19.5-27.1), and 27.8 (22.1-34.9) per 100-PY for any infection; and 3.1 (2.3-4.1), 5.5 (3.5-8.6), and 7.0 (4.1-12.0) per 100-PY for SARS-COV-2 infections in 1L, 2L and 3L+ cohorts, respectively. Conclusions: This real-world analysis demonstrated substantial morbidity and mortality associated with overall and SARS-COV-2 infections among NHL patients, with a higher incidence in DLBCL compared to FL, and with increasing LoTs.
Impact of military deployment on non-Hodgkin lymphoma subtype.
Authors: Sgrignoli Robert , Rendo Matthew , Fenderson Joshua L. , Morris Michael , Kou Chung-ting Jimmy , Aden James , DeStefano Christin 
Published: June 2024

e19070 Background: Approximately 3.5 million activity duty service members (ADSM) have deployed to Afghanistan or Iraq from 2001-2022. During deployments, ADSMs are potentially exposed to deployment-related toxins and carcinogens, which could theoretically alter cancer biology. In terms of non-Hodgkin lymphoma (NHL), it is unclear whether deployment affects NHL subtype or cancer-specific survival. Methods: Deployment and occupation data from the Defense Manpower Data Center was merged with data from the Department of Defense Tumor Registry. Documented cases of NHL diagnosed from 2001-2022 were identified. ADSMs and retirees were included; dependents and those under the age of 18 were excluded. Differences in NHL subtype (aggressive B-cell, indolent B-cell, T-cell) and cancer-specific survival were assessed by deployment status (previously deployed vs. never deployed). Occupation was assessed among those who deployed. Propensity score matching (2:1) for age at diagnosis, year of diagnosis, and gender was performed to minimize confounding. All data were carried out using SAS and Jump statistical software. This study was approved by the IRB. Results: There were 2,599 ADSMs and retirees diagnosed with NHL between 2001-2022. Approximately 15% had previously deployed (n=398). Compared with never deployed, military personnel who had previously deployed were more likely to have aggressive B-cell NHL (45% vs. 34%) and less likely to have indolent B-cell NHL (50% vs. 54%) or T-cell NHL (6% vs. 12%), p<0.001. Deployment to Iraq or Afghanistan did not impact NHL subtype. During deployment, occupations of Infantry, Engineering and Healthcare did not impact NHL subtype, whereas occupations of Pilot/Aircrew and Intelligence did, with less T-cell lymphoma diagnosed (0 vs. 7%, and 3% vs. 8%, respectively). When evaluating NHL subtype by race, it was noted that in comparison to White, Asian, Pacific Islander and Other Race, Black Race was associated with more T-cell NHL (21%), largely comprised of cutaneous T-cell lymphoma. Conclusions: After propensity score matching, prior deployment was associated with more aggressive B-cell lymphoma than military personnel who had never deployed. Deployment occupation affected NHL subtype diagnosed, with Pilots/Aircrew and Intelligence personnel being less likely to have T-cell lymphoma, whereas Black Race was associated with a higher likelihood of having T-cell lymphoma. This study sheds insights into the impact of deployment on cancer subtype. Ongoing investigations are assessing mortality differences by deployment as well as causes of death.
Survival outcomes in primary cutaneous diffuse large B-cell lymphoma, leg type.
Authors: Baidoun Firas , Hoppe Bradford S. , Tun Han W. , Alhaj Moustafa Muhamad 
Published: June 2024

e19074 Background: Primary cutaneous diffuse large B-cell lymphoma (PCDLBCL-LT) is an uncommon type of lymphoma predominantly affects elderly patients and is associated with poor outcome. Large-scale studies describing and evaluating the effect of different type of treatments on survival outcome are lacking. Methods: The National Cancer Database (NCDB) was queried for patients diagnosed with PCDLBCL-LT between 2004 and 2020. All patients aged ≥18 years diagnosed with PCDLBL-LT were included. We excluded patients with unknown chemotherapy and radiation therapy status or lost to follow-up (unknown vital status of last contact). Kaplan-Meier and multivariate Cox regression were used in the analyses. Results: The total cohort consisted of 967 patients with PCDLBCL-LT. Out of whom 516 (53%) were females, 841 (87%) were White non-Hispanic, 41 (4%) were White Hispanic and 37 (4%) were African Americans. 276 (29%) received chemotherapy, 203 (21%) received radiation only, 293 (30%) received chemoradiation, 147 (15%) did not receive any treatment and 48 (5%) had unknown treatment status. The median age at diagnosis was 78 years (range 23-90). The median follow-up time was 87 months (95% CI 74-99), the median overall survival (mOS) for the whole cohort was 42 months (95%CI 37-47). Among patients with known treatment status and vital status of last contact (N=841), patient who received chemoradiation had significantly better mOS compared to patients who received chemotherapy only, radiation only and no treatment (64 vs 41, 39 and 9 months, respectively P<0.001). Patient who received chemotherapy only and radiation only as first line therapy had significantly better mOS compared to patients who received no treatment (41 and 39 vs 9 months, respectively P<0.001), but there was no statistically significant difference in the mOS between chemotherapy only and radiation only (41 vs 39 months, P=0.359). On multivariate analysis, older age, male gender, and Charlson-Deyo score 2 and ≥3 were associated with worse OS (HR 1.061 95%CI 1.050-1.072; P<0.001, HR 1.241 95%CI 1.093-1.482; P=0.017, HR 1.396 95%CI 1.004-1.941; P=0.047 and HR 2.454 95%CI 1.619-3.719; P<0.001 respectively), all type of treatments including chemotherapy only, chemoradiation, and radiation only were associated with better OS (HR 0.576 95% CI 0.443-0.749; P<0.001, HR 0.379 95%CI 0.290-0.495; P<0.001 and HR 0.443 95%CI 0.339-0.578; P<0.001, respectively). Conclusions: This large real-world analysis shows a survival benefit with combined treatment of chemoradiation in this uncommon type of lymphoma compared to single treatment modality.
Racial disparities in major adverse cardiovascular and cerebrovascular events in patients with non-Hodgkin lymphoma.
Authors: Raval Maharshi , Uttam Chandani Kanishka , Agrawal Siddharth Pravin , Eldimllawi Ahmed Medhat , Siddiq Sajid , Nadeem Ahmed , Chintakuntlawar Ashish V. , Hashmi Shahrukh K. 
Published: June 2024

e19076 Background: Non-Hodgkin Lymphoma (NHL) is the seventh most prevalent cancer and has sixth highest malignancy mortality in United States. Owing to the advances in treatment of NHL including targeted therapies, the survival of NHL patients has increased over the past decades. However, inequalities may exist in the access to advanced care, clinical trials, and subspecialist appointments in certain patient populations. We aim to study the racial disparities in major cardiovascular and cerebrovascular events (MACCE) in NHL patients. Methods: Using ICD-10 codes, patients with NHL were identified from National Inpatient Sample 2019 database. We included all-cause in-hospital mortality (ACIHM), acute myocardial infarction (AMI), atrial fibrillation (AF), cerebrovascular accident (CVA), and sudden cardiac death (SCD) as MACCE for the outcomes. Baseline characteristics including demographics, comorbidities; and MACCE outcomes were studied using chi-square for categorical or ANOVA for continuous data (statistical significance determined as p-value <0.05) and results were stratified based on patient’s races. Results: Out of the total sample size of 205220 patients admitted with a diagnosis of NHL, 74.94% (153785) were White, 8.95% (18370) were Black, 9.46% (19415) were Hispanic, 3.48% (7140) were Asian/Pacific Islander, 0.42% (875) were Native American, while 2.75% (5635) belonged to other races. When compared to White patients, ACIHM was significantly higher in Black patients with adjusted odds ratio (aOR) of 1.294 (95% CI 1.099-1.523, p=0.002) and Asian/Pacific Islander patients (aOR 1.279, 95% CI 1.005-1.628, p=0.045). Risk of AMI was lower in Black patients (aOR 0.751, 95% CI 0.587-0.96, p=0.023) as compared to White patients. AF risk was significantly lower in Black, Hispanic, and Other race patients compared to White patients. The odds of developing CVA are higher in Asian/Pacific Islander patients (aOR 1.285, 95% CI 1.002-1.649, p=0.048) and of having SCD are higher in Black patients (aOR 2.052, 95% CI 1.5-2.806, p<0.001) when compared to White patients. Conclusions: In patients with NHL, Black patients had higher ACIHM and SCD while Asian/Pacific Islander patients had higher ACIHM and CVA when compared to White patients. Although the reason of disparity is likely multifactorial, the findings of this study highlight the need for development of healthcare strategies stratified by race which may aid to mitigate the increased risk of MACCE in certain races. Further research involving possible genetic influences and social determinants of health contributing to poorer outcomes in Black and Asian/Pacific Islander patients with NHL becomes imperative.
Incidence, characteristics and outcomes in relapsed and refractory CD20+ PTLD: An institutional retrospective cohort study.
Authors: El-amir Zain , McLane Michael Joseph , Kaminski Mark S. , Phillips Tycel Jovelle , Wilcox Ryan A. , Sano Dahlia , Karimi Yasmin , Carty Shannon 
Published: June 2024

e19078 Background: Post-transplant lymphoproliferative disorder (PTLD) is a malignancy with significant morbidity and mortality after solid organ transplant (SOT). Frontline treatment of CD20+ PTLD is well established; however, there is a lack of data on the treatment of relapsed/refractory (R/R) PTLD, especially in the era of novel therapies approved since 2017 for diffuse large B-cell lymphoma. Methods: We conducted a single institution retrospective study of adult SOT patients with CD20+ PTLD. Inclusion criteria were age ≥18 and use of an adult regimen that included rituximab for frontline therapy. Baseline and pathologic characteristics, frontline and subsequent treatments, response rates, and toxicities were collected. Results: 71 cases of CD20+ PTLD were diagnosed between 01/01/2012 to 12/31/2022. The median age at diagnosis was 46. SOTs included kidney (46.5%), liver (21.1%), lung (16.9%), heart (14.1%), and pancreas (1.4%). Pathologically, 47 cases were monomorphic (12 germinal center B-cell-like [GCB] subtype, 26 non-GCB subtype, 9 cases indeterminate), 12 were polymorphic, 2 were non-destructive, and 10 were unclassified. 38 cases (53.5%) were Epstein-Barr virus positive. Frontline treatments included rituximab followed by R-CHOP (38.0%), rituximab monotherapy (16.9%), R-EPOCH (4.2%), and R-miniCHOP (2.8%). Toxicities included acute kidney injury (21.1%) and perforation (9.8%) and rejection (7%). The median overall survival (OS) was 62 months. 21 (29.6%) patients relapsed (N = 13) or were refractory (N = 8) to frontline treatment. Median time to relapse was 12.0 months. Systemic treatments included RCHOP, R-miniCHOP, RICE, R-Gemcitabine and oxaliplatin (R-GemOx), lenalidomide/tafasitamab (len/tafa), and R-ibrutinib with an overall response rate (ORR) of 72.2% in the second line setting; 50% of patients required dose reductions. Median OS was 17 months. Progression-free survival (PFS) was 4.5 months. The. ORR, median PFS and OS among those who received novel therapy (N=3) was 100%, 4.4 months, and not reached compared to 66.7%, 8 months, and 4.6 months with traditional cytotoxic therapy (N=15), respectively. 6 patients received a third line of therapy, which included polatuzumab-BR, CAR-T cell therapy, R-GemOx, len/tafa, and loncastuximab. ORR was 80%. 33% of patients required dose reductions. At data cutoff, 2 patients who received a third line of therapy were alive with stable disease on therapy. Causes of death in third line treatment included perforation (N=1), COVID (N = 1), fungemia (N=1), and cardiac arrest likely unrelated to PTLD (N = 1). 3 patients who died had active PTLD at time of death. No patients experienced graft rejection during treatment for R/R PTLD. Conclusions: R/R CD20+ PTLD after SOT remains a therapeutic challenge. Better understanding of cytotoxic versus novel therapies can help guide clinical decision making.
CSF proteomics for predicting response to treatment in patients with primary and secondary central nervous system lymphoma.
Authors: Wilding Hannah E. , Aastha Aastha , Mikolajewicz Nicholas , Macedo Filho Leonardo , Bhanja Debarati , Heebner Madison , Khan Shahbaz , Ignatchenko Vladimir , Ozair Ahmad , Ahluwalia Manmeet Singh , Glantz Michael J. , Kislinger Thomas , Mansouri Alireza 
Published: June 2024

e19083 Background: Despite exquisite responses to initial therapy in patients with CNS lymphoma (CNSL), relapse is common and overall responses are disappointing compared to other non-CNS diffuse large B-cell lymphomas. Incorporation of multi-agent intraventricular chemotherapy (MAIVC) alongside systemic therapy is a novel strategy. To maximize MAIVC benefit, identification of minimally-invasive biomarkers for guiding patient management is necessary. This study sought to identify cerebrospinal fluid (CSF)-based proteomic predictive biomarkers for MAIVC treatment response at baseline and for longitudinal monitoring of tumor burden in CNSL. Methods: A retrospective study of patients with primary or secondary CNSL that were treated with MAIVC at Penn State Health (2015-2021) was conducted and reported following REMARK guidelines. Each MAIVC cycle was administered via Ommaya reservoir and included a 2-drug combination comprised of methotrexate, rituximab, cytarabine, etoposide, topotecan, gemcitabine, or thiotepa. Patient-matched CSF was sampled at pre- and post-therapeutic endpoints and profiled using shotgun proteomics. Patients were grouped by treatment response status. Early responders were defined as patients achieving malignant-cell-free CSF within 6 MAIVC cycles, whereas never responders were those patients that i) did not achieve malignant-cell-free CSF by endpoint or ii) required salvage surgery or radiation during MAIVC. Results: 59 patients were included (21 primary; 38 secondary CNSL) with a median age of 66 years (range 25-90) and median number of MAIVC cycles of 8 (range 2-23). Only 1 required Ommaya removal secondary to infection. A proteomic-based classifier, comprised of SGCE, LCP1 and AGRN, discriminated between early and never responders with AUROC of 0.95. Comparison of CSF at baseline (<3 cycles MAIVC) vs. post-treatment (>12 cycles MAIVC) identified H3F3A, YWHAE, LCP1, CA1 and GAPDH as tumor burden biomarkers. Conclusions: Here we developed a proteomic signature capable of predicting CNSL patient response to MAIVC, with potential to improve clinical decision making. Furthermore, the biomarkers associated with tumor burden represent important indicators of treatment response. Ongoing efforts are underway to evaluate these candidates in independent validation cohorts.
Efficacy and safety of GPRC5D-based monotherapies for relapsed/refractory multiple myeloma: A systematic review and meta-analysis.
Authors: Shrestha Asis , Adhikari Ayush , Rayamajhi Sandesh , Gouli Sugam , Shrestha Jasmine , Niraula Sujan , Neupane Niraj , Al Hadidi Samer 
Published: June 2024

e19503 Background: G protein-coupled receptor family C group 5 member D (GPRC5D), a highly expressed receptor in myeloma cells, is one of the novel emerging targets for relapsed/ refractory (R/R) multiple myeloma (MM). Among the GRPC5D therapies, currently one agent talquetamab has been approved while CAR-T therapies are under development. Methods: A literature search using electronic databases Pubmed, Embase, Scopus, Web of Science and Cochrane, including major conference abstracts was conducted from inception to December 31, 2023 focusing on GPRC5D therapies in MM. For multiple reports of the same study, the latest available report of the study describing the efficacy or safety was selected. Only GPRC5D based monotherapies were included, and combination regimens were excluded for this review. Data on safety and efficacy were extracted, evaluated and systematically analyzed using Comprehensive Meta-analysis 3.3. The study protocol was registered with PROSPERO (CRD42024497933). Results: After screening 562 articles, and removing duplicates, total seven studies with 581 patients were included (5 GPRC5D-CAR T studies with 137 patients and 2 GPRC5D-BsAb studies with 444 patients). The pooled overall response rate (ORR) for GRPC5D therapies in this cohort was 77.4%, with best response rate [very good partial response (VGPR) or better] of 59.2%. The pooled incidence rate of cytokine release syndrome (CRS), any grade and Immune effector cell-associated neurotoxicity syndrome (ICANS), any grade, was 78.8% and 9.6% respectively. Grade 3/4 hematological adverse events included neutropenia being the most common (69.6%), followed by thrombocytopenia (36.8%) and anemia (34.2 %). Subgroup analysis was performed for GPRC5D therapies- CAR T and BsAb as shown in the table. Conclusions: GPRC5D based therapies showed high response rates in R/R MM with distinct side effect profile including CRS and cytopenias. Further studies along with follow up of the ongoing trials is needed to understand the long-term outcomes. [Table: see text]