bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of congestive heart failure with hospital outcomes among patients with chronic lymphocytic leukemia in the United States: Analysis of nationwide inpatient sample.
Authors: Olusoji Rahman Adesoji , Idowu Abiodun , Adabale Olanrewaju , Mohamed Salih Rajaa , Omore Ibrahim , Ahluwalia Meena 
Published: June 2023

e19506 Background: Chronic Lymphocytic Leukemia (CLL) is adults' most prevalent chronic leukemia. There is an increased report of cardiovascular comorbidities in these patients due to the multi-systemic impact of both the insidious disease and the associated side effects of its treatment. This study aimed to provide real-world contemporary data on the in-hospital outcomes among patients admitted for CLL with comorbid Congestive Heart Failure (CHF) in the United States. Methods: The study is a retrospective study that used the National Inpatient Sample database. We identified patients hospitalized for CLL from 2018-2020 and stratified them into two cohorts – with CHF and without CHF. Inclusion criteria include age ≥ 18 years and hospitalization primarily for active CLL. We excluded patients with aortic stenosis and those whose CLL were in remission. Inferential statistics - chi-squared test and Student t-test (as applicable) - was done on extracted data. The odds ratio was calculated using univariate and multivariate analyses. All analyses were done at a 95% confidence interval with a 2-tailed p-value <0.05 set as the cut-off for statistical significance. Results: A total of 210,012 hospitalizations of CLL were identified, of which 27.5% (57,650) had comorbid CHF. On univariate logistics regression analysis, the average length of hospitalization was statistically (p<0.001) prolonged by one day, and the cost of hospitalization increased by 9,640 + 1482 US dollars among those with CHF and active CLL. The odds of all-cause in-hospital mortality increased by 1.6 folds in these patients (P<0.001). However, after adjusting for individual patients and hospital-level cofounders, active CLL did not have a significant clinical impact on the duration and total cost of heart failure hospitalization. Active CLL, however, significantly increased the risk of all-cause in-hospital mortality by 1.3 folds (4.7% vs 7.2%; adjusted odds ratio 1.31, 95% CI 1.17-1.46; p<0.01) in patients with heart failure. Conclusions: Patients hospitalized for active CLL with a comorbid diagnosis of CHF have increased odds of in-hospital mortality compared to those without comorbid heart failure. This finding suggests the need for integrative multi-disciplinary care for CLL patients with comorbid CHF, such as cardio-oncology.
Efficacy of immune checkpoint inhibitors for the treatment of advanced melanoma (AM) in patients with concomitant chronic lymphocytic leukemia (CLL).
Authors: Cass Samuel , Tobin Joshua , Seo Yongwoo David , Gener-Ricos Georgina , Keung Emily Zhi-Yun , Burton Elizabeth M. , Walsh Danielle M. , Davies Michael A. , McQuade Jennifer Leigh , Lazar Alexander J. , Hampel Paul Joseph , Wargo Jennifer Ann , Ferrajoli Alessandra 
Published: June 2023

e19511 Background: CLL is the most prevalent adult leukemia and is associated with an increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICI in patients with CLL. Immune checkpoint inhibitors (ICI) have revolutionized management of AM, but data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. We, therefore, sought to examine the efficacy of ICI for melanoma in patients with concomitant CLL and AM. Methods: In this international and multicentre retrospective study, review of clinical databases identified patients with concomitant CLL and AM treated with ICI from two US tertiary cancer centers (n = 39) and an Australian multi-institutional experience (AUS, n = 19). Objective response rates (ORR), defined as complete or partial response by RECIST v1.1, and survival outcomes (overall survival, OS, and progression-free survival, PFS) among patients with CLL and AM were assessed. Clinical factors associated with improved ORR and survival were explored. Results: Between 1997 and 2020, 58 patients with CLL were treated with ICI for concomitant AM. Among all patients with CLL and AM, ORR to ICI was 41% and median duration of response was 18 months. A majority were untreated for CLL (64%) at the time of ICI. Patients with prior history of treatment for CLL had significantly reduced ORRs (21% vs 51%, p = 0.04), PFS (3.6 vs. 14.6 months, p = 0.005), and OS (7.4 vs. 52.2 months, p = 0.002), compared to patients on observation for their CLL. Prior treatment with T-lymphocyte depleting chemoimmunotherapy (fludarabine, bendamustine, and alemtuzumab) was particularly associated with poor outcomes (median OS of 7.0 months, median PFS of 3.4 months). On univariate analysis, prior treatment for CLL, high risk CLL 17p deletion, and higher CLL Rai stage were associated with shorter PFS from ICI, though CLL treatment was the only factor independently associated with shorter PFS in the multivariate model (HR 6.5, [CI 2.1-20.3], p = 0.001]. Overall, 3 patients developed CLL progression while on ICI, though in two of these patients, the AM had an objective, durable clinical response to ICI. Overall, immune-related adverse events (irAE) occurred following 38% of ICI and rates of irAE were similar by CLL treatment status. Conclusions: Our case series of patients with concomitant CLL and melanoma demonstrate frequent, durable clinical responses to ICI However, those with prior chemoimmunotherapy treatment for CLL had significantly worse outcomes. We found that CLL disease course is largely unchanged by treatment with ICI.
Incidence and outcomes of immune-related adverse events after immune checkpoint inhibitors in patients with Hodgkin lymphoma.
Authors: Lin Cindy (Hsin-Ti) , Tse William W. , Wang Jiasheng 
Published: June 2023

e19513 Background: Immune checkpoint inhibitors (ICIs) have recently been found to be effective in Hodgkin lymphoma (HL). However, given the impaired systemic immune response in HL, it is unclear whether immune-related adverse events (irAEs) would manifest differently in this population; data on this topic remains scarce. Methods: Data were collected from an aggregated electronic medical record (EMR) database TriNetX Research Network (TriNetX LLC., Cambridge, Massachusetts, USA). Adult patients diagnosed with HL who received pembrolizumab or nivolumab between 1/2018 and 1/2022 were included. irAEs were identified through a set of validated ICD-10-CM codes. Results: Within the study period, a total of 567 patients with HL were identified. Among them, 363 (63.8%) patients received nivolumab and 263 (46.4%) received pembrolizumab. The mean age was 50.1 (SD 19.6) years-old, 227 (40.0%) patients were female, 69 (12.2%) were black, and 156 (27.5%) received ICI-based therapy as the frontline treatment. irAE of any grade occurred in 280 (49.4%) of patients. Patients who experienced irAEs were more likely to be older (p = 0.0106), while using ICIs as the frontline or after various previous treatments was not associated with irAEs (Table). Among specific irAEs, skin toxicities, thyroid dysfunction, pneumonitis, colitis, and hepatitis occurred in 31.6%, 23.6%, 2.8%, 9.3%, and 3.2% of patients, respectively. Regarding the management for irAEs, systemic steroids, topical steroids, mycophenolate, and infliximab were used in 63.6%, 36.8%, 3.6%, and 3.6% of patients, respectively. Of note, ICIs were able to be resumed in 71.1% of patients with irAEs. After propensity-score matching for known prognostic factors for HL, patients with or without irAE had similar overall survival (OS) (hazard ratio 0.84, 95% confidence interval 0.57 to 1.23, p=0.36). No significant difference of OS was seen across different subtypes of irAE, including skin toxicities (p=0.64), thyroid dysfunction (p=0.74), or colitis (p=0.28). Conclusions: irAEs were common in patients with HL receiving ICIs. The majority of patients with irAEs were able to resume ICIs, and the development of irAEs did not affect overall survival. [Table: see text]
Hodgkin lymphoma mortality trends in age subgroups from 1999 to 2020 in the United States.
Authors: Varughese Tony , Koprivnikar Jamie 
Published: June 2023

e19515 Background: Hodgkin Lymphoma has a bimodal distribution with the first peak between ages 15-35 and the second peak being 55 years old and older. Advancements in treatment therapies have improved mortality such that Hodgkin Lymphoma is considered a curable disease. However, treatment outcomes in elderly patients are inferior to those of younger patients. In our study, we analyzed Hodgkin Lymphoma mortality from 1999 to 2020 in the United States. We investigated age-adjusted mortality rates and annual percent changes with a sub-group analysis. Methods: Using the CDC Wonder database, we examined mortality trends from 1999 to 2020 for Hodgkin Lymphoma in adults age 55 and older in the United States. Age-adjusted mortality rates (AAMRs) were calculated per 100,000 people and stratified patients by sex, race/ethnicity, and census region. We computed the annual percentage change trends for the respective stratification using Joinpoint regression software. Additionally, a comparison group between ages 15 and 54 was added for the analysis. Results: In the United States, between 1999 and 2020 there were 24,898 deaths from Hodgkin Lymphoma in Adults 55 and older. The overall age adjusted mortality rate improved from 1.9 per 100,000 people to 1.4, with a respective APC of -2.06%. Our subgroup analysis by sex, race, and census region showed improvements circumferentially. Males consistently had higher rates of improvement than females. Most notably black patients had the lowest difference in AAMR from 1999 to 2020 (0.2), however, white patients and Hispanic patients respectively had higher AAMRs. The comparison group ages 15-54 had lower AAMR change from 1999 to 2020 by sex, race, and region. However, the respective AAMR for the age 15-54 group was significantly lower. Conclusions: Hodgkin Lymphoma has had significant age adjusted mortality rate improvements since 1999. Comparing adults 55 and older to patients 15-54 there is still a notable difference in AAMR. The greater magnitude of improvement in AAMR in older adults with Hodgkin Lymphoma may be related to the approval of agents such as brentuximab vedotin, which has improved tolerability as compared to bleomycin. Alleviating pulmonary toxicity with this novel agent may be more relevant in an older patient population with increased comorbidities. Further, research is needed to continue to identify more efficacious and less toxic therapies for older individuals with Hodgkin Lymphoma. [Table: see text]
Five-year subgroup analysis of tafasitamab + lenalidomide from the phase II L-MIND study in patients with relapsed or refractory diffuse large B-cell lymphoma.
Authors: Duell Johannes , Abrisqueta Pau , Dreyling Martin H. , Gaidano Gianluca , González Barca Eva , Jurczak Wojciech , Maddocks Kami J. , Menne Tobias , Tournilhac Olivier , Bakuli Abhishek , Amin Aasim , Gurbanov Konstantin , Salles Gilles A. , Nagy Zsolt 
Published: June 2023

e19522 Background: The Phase II L-MIND study led to accelerated US approval and EU conditional authorization of the CD19-targeted immunotherapy, tafasitamab, + lenalidomide (LEN) followed by tafasitamab monotherapy for patients (pts) with R/R DLBCL ineligible for autologous stem cell transplant (ASCT). Long-term L-MIND data further support the regimen. Here we present exploratory analyses of final 5-year (yr) efficacy in subgroups of interest. Methods: Pts (≥18 years) with ASCT-ineligible R/R DLBCL, 1–3 prior systemic therapies (incl. ≥1 targeting CD20) and ECOG PS 0–2 received tafasitamab for ≤12 28-day cycles (+ LEN), then alone until disease progression. Primary endpoint was objective response rate (ORR). Secondary endpoints included duration of response (DoR), progression-free survival (PFS) and overall survival (OS). Exploratory subgroup analyses including by International Prognostic Index (IPI) and time to progression after 1L (in pts with only 1 prior line) used Kaplan-Meier estimates of 5-yr endpoints. Results: As of 14 Nov, 2022 in the full analysis set (FAS; n=80), ORR was 56.2% [95% CI: 44.7–67.3]. Median treatment duration was 9.0 months (mo) [0.5–73.6] and median follow-up (mFU) for OS was 65.6 mo [59.9–70.3]). Median DoR was not reached (mFU: 43.7 mo [29.9–58.4]). Of 18 patients in follow-up for ≥5 years, 9 received tafasitamab until end of study per protocol, 9 discontinued while in remission. RR and 5-yr rates for DoR, PFS and OS showed long-term clinical activity in all pt subgroups (Table). Conclusions: In this 5-yr subgroup analysis, a long-term clinical benefit with tafasitamab + LEN followed by tafasitamab monotherapy was observed in all subgroups of clinical interest, including pts with poor prognosis risk factors. These data suggest this immunotherapy may have curative potential, which is being explored in further studies. Clinical trial information: NCT02399085 . [Table: see text]
Multicenter real-world study of newly diagnosed advanced-stage extranodal natural killer/T-cell lymphoma (ENKTL): Proposal for intensive therapy.
Authors: Wei Yu-Ce , Fei Qi , Zheng Bao-Min , Xie Yan , Chen Bo , Liu Wei-Xin , Zhang Changgong , Liu Weiping , Fang Hui , Qi Shunan , Zhang Di , Chai Yue , Li Ye-Xiong , Wang Wei-Hu , Song Yuqin , Zhu Jun , Dong Mei 
Published: June 2023

e19523 Background: Advanced-stage ENKTL is characterized by its low prevalence, poor prognosis, and inconclusive optimal therapy. The present study investigated the treatment of newly diagnosed advanced-stage ENKTLs. Methods: Newly diagnosed stage III/IV ENKTL patients from two large-scale Chinese cancer centers in the last 10-15 years were retrospectively collected and analyzed. Results: With a median follow-up of 75.03 (range, 0.33-292.13) months, the median overall survival (mOS) for the 195 newly diagnosed stage III/IV ENKTL patients was 19.43 (range, 0.33-292.13) months, and estimated 1-, 2-, 3-, and 5-year OS were 59.5%, 46.3%, 41.8%, and 35.1%, respectively. First-line multi-modality therapy(n=89) significantly prolonged OS compared to single-modality therapy(n=106)( P<0.001). Chemotherapy(CT)+radiotherapy(RT)(n=47) compared to CT alone(n=93)( P=0.007), and hematopoietic stem cell transplantation(HSCT)(n=20) compared to non-HSCT(n=175)( P<0.001) both significantly improved OS. For patients ≤60 years and ineligible for HSCT, other therapies with complete remission(n=28) led to comparable OS( P=0.160), with no significant difference in baseline characteristics( P>0.05). Four long-term survival patients treated with chidamide maintenance therapy(MT) achieved a median progression-free survival(PFS) of 55.83(range, 53.27-92.33) months and a mOS of 60.65(range, 53.70-95.70) months, preliminarily indicating its positive impact on prognosis. Regarding CT, anthracycline(ANT)-based regimens(n=60), compared to non-ANT-based ones(n=119), led to significantly inferior PFS( P=0.031) and OS( P=0.010); while asparaginase(ASP)-(n=123) compared to non-ASP-(n=56), and gemcitabine(GEM)-(n=56) compared to non-GEM-based(n=123) regimens, both prolonged PFS( P=0.005; P=0.009) and OS( P=0.086; P=0.003). Multivariate analysis further showed that GEM-based regimens improved PFS(HR=0.691, P=0.061) and OS(HR=0.624, P=0.037) compared to non-GEM-based ones. The GEM+ASP(n=42) combinations slightly improved PFS and OS compared to regimens containing either GEM(n=14) or ASP(n=56) alone( P>0.05). The GEM+ASP combinations led to significantly superior PFS( P=0.058[log-rank test], P=0.036[Breslow test]) and OS( P=0.008) compared to the ANT+ASP combinations. First-line “intensive therapy”, including CT(particularly GEM+ASP regimens), RT, HSCT, and chidamide MT, was therefore proposed, and could improve long-term survival for advanced-stage ENKTLs. Conclusions: We propose the first-line “intensive therapy” for newly diagnosed advanced-stage ENKTLs, including CT, RT, HSCT, and chidamide MT. The GEM+ASP combinations appear to yield the optimal efficacy and survival. RT, consolidative HSCT, or chidamide MT are recommended.
Real-world treatment patterns of bruton tyrosine kinase inhibitors (BTKi) in patients with mantle cell lymphoma (MCL) in community oncology practices in the United States (US).
Authors: Shah Bijal D. , Xue Mei , Yang Keri , Liu Sizhu , Tang Boxiong 
Published: June 2023

e19525 Background: Real-world data on BTKi use in MCL remain limited. This study aimed to examine US real-world BTKi treatment pattern, duration, and adherence in MCL patients. Methods: This retrospective observational study used electronic medical records (EMR) data from Integra Connect database in 18 US community-based oncology practices. Adults with MCL diagnosis on ≥2 separate dates who started BTKi therapy between 1/1/2019 and 11/30/2021 were included. EMR data was collected to ensure adequate medical history and ≥6-months follow up period. Index date was defined based on the use of one of the 3 BTKi: zanubrutinib, acalabrutinib, and ibrutinib for 3 BTKi patient cohorts. Baseline comorbidities were collected ≤90 days prior to index date based on diagnosis records. Sociodemographic and clinical characteristics, comorbidities, and treatment patterns were examined by each BTKi group. Treatment duration was calculated based on EMR and claims until end of follow up. Discontinuation data was based on unstructured physician notes. Kaplan-Meier analysis was used to compare treatment duration between the 3 BTKi groups. Results: In 402 MCL patients identified to start BTKi therapy (44 zanubrutinib; 161 acalabrutinib; 197 ibrutinib), the median age (range) at BTKi therapy start was 75 (56-89) years in zanubrutinib, 76 (36-89) in acalabrutinib, and 72 (36-89) in ibrutinib group ( P<0.01; Table). There is no significant difference between the 3 BTKi groups in other baseline characteristics. Half of zanubrutinib patients used other BTKi in prior therapy, with 31.8% switched from other BTKis to zanubrutinib ≤60 days of treatment start. In acalabrutinib group, 29% had prior BTKi use. Given a later approval date, zanubrutinib group had a relative shorter mean follow-up period (493 days [d]) vs acalabrutinib (701 d) and ibrutinib (746 d). Nevertheless, zanubrutinib patients had significantly longer median treatment duration (292 d) vs acalabrutinib (259 d) and ibrutinib (149 d) ( P<.01). Conclusions: Real-world EMR data from US community-based oncology practices suggested significantly longer treatment duration and adherence in MCL patients treated with zanubrutinib compared with acalabrutinib or ibrutinib. Further analyses on long term utilization are needed upon data maturation. [Table: see text]
Risk reduction of CNS relapse in diffuse large B cell lymphoma with intrathecal methotrexate prophylaxis: A single institution retrospective study.
Authors: Hino Christopher , Lacy Curtis , Brothers Joel M. , Cao Huynh Le , Mirshahidi Hamid R. , Park Kiwon , Akhtari Mojtaba 
Published: June 2023

e19531 Background: Central nervous system (CNS) relapse is an infrequent but serious and challenging complication in diffuse large B-cell lymphoma (DLBCL) that carries a dismal prognosis. While several risk factors have been identified to stratify the risk for CNS relapse including the 2015 CNS internal Prognostic index (CNS-IPI), controversy still remains regarding the indication, timing, and method of CNS prophylaxis. The purpose of this study was to determine whether IT-MTX reduced the risk of CNS relapse, as well as treatment related and financial toxicity of CNS prophylaxis. Methods: We performed a single-center, retrospective analysis on a cohort of 192 patients with DLBCL who had received treatment between January 2010- August 2022. Patients were identified by using ICD10 code diagnosis in the electronic medical records system. We included patients of all stages of disease and CNS-IPI scores along with patients with testis, breast, sinus, and bone marrow extranodal involvement. Patients with primary CNS disease and primary mediastinal disease were excluded from the study. Clinical data collected by chart review included age at time of diagnosis, sex, performance status, LDH level, disease stage, number and type of therapies administered including IT-MTX, extranodal involvement, MYC/BCL2/BCL6 translocation status, HIV status, cell of origin (COO), treatment response. Toxicities and complications thought to be associated with IT-MTX prophylaxis were also documented in addition to total costs of treatment for each patient. Patient characteristics were compared using Fisher exact test or Pearson’s chi-square test. Results: In patients with intermediate to high CNS relapse risk (CNS-IPI 2-5) IT-MTX did not reduce the 1 year risk of CNS relapse (RR 1.1296, 95% CI 0.1933 to 6.6012, P = 0.08924). The median time to CNS relapse was longer in patients who had received IT-MTX (13.5 months) vs those who did not (7 months). Thirty eight (52.8%) patients reported adverse side effects of any kind as a result of IT-MTX administration, with 23.6% of patients developing grade 2-3 adverse events. The average cost for CNS-prophylaxis was estimated to be approximately $8,059.04 over a patient’s treatment course, but as high as $20,140. Conclusions: In conclusion, our study highlights the necessity to develop improved standardized guidelines for use of CNS prophylaxis in patients with DLBCL. The results from our retrospective study add to the growing body of literature showing IT-MTX has limited and potentially transient effectiveness in preventing CNS relapse. Given the high rate of side effects and significant cost of IT-MTX, we recommend that clinicians carefully consider the risks and benefits of prophylaxis before prescribing IT-MTX for CNS-prophylaxis.