bluuebunny/crossref_metadata_2025_split huggingface dataset:
Weekend effect on TLS admission in patients with acute leukemia and lymphoma: Nationwide analysis of mortality, HD, demographics and health care utilization.
Authors: Obeidat Khaldun , Tariq Muhammad Junaid , Gupta Shweta 
Published: June 2022

e19582 Background: Tumor lysis syndrome (TLS) is a well-known complication of hematological malignancies including leukemia and lymphoma which can occur after chemotherapy or spontaneously, early recognition of TLS can be challenging sometimes. We attempted to evaluate the Weekend effect on TLS outcomes. Methods: Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS) was queried to identify TLS admissions between 2016-2018 in patients with diagnosis of acute leukemia and lymphoma. We studied socio-demographic differences, all-cause mortality, acute renal failure and dialysis. Secondary outcomes included mean length of stay (LOS), mean total hospital charges (THC). Statistics were performed using the t-test, univariate and multinomial logistic regression. Results: A total 1595 TLS admissions were identified (51% in lymphoma and 49% in acute leukemia), weekend admissions were 14.4% of total admissions. There was no significant difference in the baseline characteristics between the 2 groups including mean age, sex, race, median household income national quartile for patient zip code, insurance, region of hospital and location/teaching status of the hospital. Total 195 (12%) patients died in the total study group; Mortality rate among patients with lymphoma was 16% while those with leukemia was 9%. Overall mortality rate among the Weekend group compared to weekday group was insignificantly higher (20% vs 11% with P = 0.11, aOR 1.4 CI 0.56-3.46 p = 0.53). Mortality in the Weekend group was significantly higher in patients with lymphoma (30% vs 13% P = 0.04) while in leukemia patients there was no significant weekend effect (8% vs 9% P = 0.83). Total 1170 patients developed acute renal failure (aOR 1.56 Cl 0.64-3.9 p 0.32) of which 30 required dialysis, none of them was admitted in the weekend group. Mean LOS for the whole cohort was 6.47 days and mean THC was $94,954 with no significant difference between the 2 groups. Conclusions: All-cause mortality was significantly higher in patients with TLS and lymphoma admitted on the weekend (p = 0.04) compared to weekday while no weekend effect was found in TLS admissions in leukemia. Further studies are needed to clarify if this higher mortality may be associated with delay in TLS diagnosis over weekend admissions in lymphoma patients.
Post hoc analysis of a long-term safety extension study: Responses to siltuximab in idiopathic multicentric Castleman disease patients receiving on-label dosing.
Authors: Rossi Jean-Francois , Zinzani Pier Luigi , Casper Corey , Voorhees Peter M. , Fayad Luis , Kanhai Karan , Kurzrock Razelle , Van Rhee Frits 
Published: June 2022

e19586 Background: Siltuximab is the only FDA- and EMA-approved therapy for idiopathic multicentric Castleman disease. Its long-term efficacy and safety were established in a 6-year extension study featuring patients who responded to treatment or had stable disease in a phase 1 or phase 2 trial. However, dosage could be adjusted at physician discretion; of 60 patients, 33 remained on the on-label dosing of 11 mg/kg administered every 3 weeks. To assess the safety and efficacy of on-label dosing, we performed a post hoc analysis in patients who maintained this dosing. Methods: A mixed-effects model was used to analyze longitudinal measurements for tumor response, C-reactive protein (CRP), hemoglobin (Hb), erythrocyte sedimentation rate (ESR), fibrinogen, albumin, and platelet counts at multiple time points. Adverse events (AEs) were also assessed. Greenhouse–Geisser correction was used to ensure that the assumption of sphericity was met for the mixed-effects model. Tukey post hoc correction was applied to determine significant differences between specific time points. Results: Of the 33 patients on 3-week dosing, one transitioned to receiving siltuximab every 6 weeks for 25 cycles but restarted 3-weekly dosing due to suspected progressive disease (PD). Disease control was observed in 31 of the 33 patients (93.9%) at their last on-study assessment (complete response [CR] in 9 [27.3%]). Quantitative analyses were performed on the 32 patients who maintained 3-weekly dosing until their last on-study assessment. Siltuximab led to sustained mean levels of CRP, Hb, ESR, fibrinogen, albumin, and platelet counts for the duration of the study. In the 19 patients with residual IL-6 activity at screening (CRP levels > 4 mg/L) there was an overall reduction in CRP from baseline at multiple time points. This group showed a trend towards improved total Hb levels, which increased by 9.43% (adjusted p = 0.048) at cycle 31, and some demonstrated an improvement in ESR, fibrinogen, and albumin levels. All patients reported AEs, mostly grade 1 or 2, with no deaths. At point of enrolment into the extension study, the three most common AEs were hypertension (36.4%), fatigue (42.4%), and pain (51.5%). Conclusions: Our findings show that long-term on-label dosage of siltuximab sustains an improved inflammatory profile and disease control.[Table: see text]
Population-wide patterns of care in mantle cell lymphoma in Australia: An analysis of the pharmaceutical benefits scheme dataset.
Authors: Tam Constantine Si Lun , Zhao Fei-Li , Liu Tom , Gauba Raj , Chuen Li Shu , Tang Boxiong 
Published: June 2022

e19587 Background: The treatment landscape in patients with mantle cell lymphoma (MCL) is changing with the introduction of Bruton’s tyrosine kinase inhibitors (BTKis) and bendamustine in Australia. We sought to analyze the practice impact of the introduction of publicly funded novel agents in MCL. The objective of this study was to describe the evolving treatment patterns of Australian patients with MCL over the last 10 years using population-wide prescription records. Methods: Patients who initiated a treatment for MCL between 01/01/2011 and 07/31/2021 were extracted from the Services Australia 10% Pharmaceuticals Benefits Scheme (PBS) dataset, which includes the dispensing records for 10% of the Australian population. This dataset captures all publicly funded treatments in Australia. The index date was defined as the commencement of any drug for MCL. First-line (1L) therapy was defined as the first treatments prescribed for MCL. A patient was defined as relapsed/refractory (R/R) if they had commenced a drug which was in a different therapeutic category, or if they re-started the same regimen after a gap of more than 180 days. Descriptive analyses were conducted to examine the use of treatment regimens for the overall 10-year population by line of therapy. Analyses by calendar year were also performed to assess the changes in the treatment patterns. Results: Overall, 241 patients with MCL were identified over the study period. The majority of patients were male (68.4%), age > 60 years (84.9%), and most being aged 70-79 years (42.1% of total). Many patients were receiving comedications at baseline, including antihypertensives (44.1%), anticoagulants (14.5%), and/or antipsychotics or antidepressants (12.5%). In the overall population (2011-2021), the majority of patients had received 1L treatment with bendamustine-rituximab (BR, 53.9%), rituximab plus other regimens (27.6%), or rituximab monotherapy (11.2%). The most commonly used regimens in R/R patients at any subsequent episode of treatment included BTKi (66.3%), rituximab monotherapy (52.8%) or rituximab plus other regimens (31.5%). A trend in adoption of novel agents was observed throughout the years following their PBS listing. Analysis by calendar year showed that from 2011 to 2020 for 1L therapy, the use of BR increased from 0% to 50% and use of rituximab-containing regimen except BR decreased from 100% to 16.7%; use of BTKi increased in R/R patients from 0% to 74.7%. Conclusions: MCL treatment patterns have significantly changed in Australia since the introduction of BTKis and bendamustine-containing regimens. The use of rituximab-containing regimens except BR in 1L MCL has decreased and use of BTKis in R/R patients has increased.
Chemo or chemo-free regimens in heavily pretreated multiple myeloma? Role of bendamustine-bortezomib-dexamethasone (BVD) in NOVEL agents' era.
Authors: Cerchione Claudio , Catalano Lucio , Nappi Davide , Ronconi Sonia , Cangini Delia , Ceccolini Michela , Musuraca Gerardo , Martinelli Giovanni 
Published: June 2022

e20010 Background: The treatment of heavily pretreated Multiple Myeloma continues to be considered as an important unmet clinical need. Bendamustine is an old bi-functional alkylating agent which has proved to be effective in relapsed, refractory and in new diagnosed Multiple Myeloma (MM). Thus, aiming to provide further insights in this field, also in novel agents’era, we present here a retrospective, real-life analysis of patients with relapsed/refractory MM (rrMM), who had received salvage therapy with bendamustine in combination with bortezomib and dexamethasone (BVD). Methods: 81 patients (44 M/37 F), with rrMM, median age at diagnosis 59.4 years (r. 36-82), median age at start of treatment 63.6 years (r.37-86) treated with several lines of treatments (median 6, r. 2-11), every refractory to all the drugs previously received (also Bortezomib), received BVD (B 90 mg/sqm days 1,2; V 1.3 mg/sqm days 1,4,8,11, D 20 mg days 1,2,4,5,8,9,11,12, Pegfilgrastim day +4) every 28 days, until progression. All patients had previously received bortezomib-based and IMIDs-based treatments, and 32% (26/81) had also received radiotherapy. 69% (56/81) had undergone single or double autologous and three (2%) allogeneic stem cell transplant. All patients were relapsed and refractory to last therapies received before BVD. Results: Bendamustine was well tolerated, with grade 3-4 transfusion-dependent anemia in 56% (46/81) of patients, and 43% (35/81) grade 3-4 neutropenia (no ospedalization was required, no septic shocks were observed). No severe extrahematologic toxicity was observed, only grade 1 gastrointestinal side effect (nausea), treated by common antiemetic drugs. According to IMWG, ORR was 63% (51/81: 7 CR, 18 VGPR, 15 PR, 11 MR) with 11 PD and 19 patients in SD, which can be considered as an impressive result in this subset of rrMM patients. In particular, for 11 patients, BVD was, after having achieved at least a PR, a bridge to second auSCT, and for two patients a bridge to alloSCT. Eight patients have surprisingly achieved a notable PR after failure of novel agents (i.e. Carfilzomib, Daratumumab and Pomalidomide). Median time to response was 1.3 months (r.1-3), median OS from diagnosis was 67.3 months (r.6-151), median OS from start of Bendamustine was 9.6 months (r.2-36). Conclusions: The triplet Bendamustine-Bortezomib-Dexamethasone has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, and, in particular cases, it could be considered as a bridge to a second autologous or allogenic SCT, also after failure of novel agents. Clinical trial information: A101.
Responses to salvage therapy in AL amyloidosis after progression on daratumumab.
Authors: Mann Hashim , Salei Yana , Fogaren Teresa , Toskic Denis , Scalia Stephanie , Ma Xun , Zhou Ping , Comenzo Ray 
Published: June 2022

e20030 Background: Daratumumab (Dara)-based therapy is the standard for upfront treatment in systemic light-chain (AL) amyloidosis and is preferred in the relapsed setting. However, outcomes of patients who relapse on dara remain unclear. In such circumstances, optimal sequencing of subsequent drugs is also not well-established. Here, we describe outcomes of AL patients who progressed on dara-based treatments. Methods: We conducted a retrospective review of AL patients treated at our center from 2015 to 2022. Patients were eligible if they progressed on dara at any time during disease course. We recorded all standard metrics, including serologic and biomarker data. Patients with incomplete follow-up or missing data were excluded. Descriptive statistics were performed with Prism 5.0 (GraphPad; San Diego, CA). Results: A total of 11 patients were identified. Median age was 73. Nine were male, and 8 had AL, λ-type (2–κ, 1–heavy chain). Median iFLC at baseline was 342 mg/L (55.6–9780) and NT-proBNP was 1166 pg/mL (147–5000). Cardiac involvement was most common (82%); 64% had ≥2 organs involved. Six had t(11;14) by FISH and/or cyclin D1 overexpression by IHC, 3 had gain 1q, 2 had del 17p, and 4 had complex cytogenetics. Five patients received ≥2 prior lines of therapy, including 3 ASCT. Three (27%) received dara in induction, whereas the most common indications for later use were hematologic/organ progression (45%), suboptimal response (18%), and refractory disease (9%). At a median follow-up of 82 weeks, all patients had progressed. Median time to next therapy was 15 weeks (7–151). Six (55%) continued dara at salvage, while other agents used were bortezomib (n=5), ixazomib (n=6), pomalidomide (n=5), cyclophosphamide (n=4), bendamustine (n=4), and belantamab mafodotin (n=3). All patients with t(11;14) or cyclin D1 overexpression received venetoclax, of whom 4 also received HMG-CoA reductase inhibitors (statins). ORR was 100%. Hematologic VGPR and CR rates were each 36%, PR 18%, and 1 patient had low dFLC PR. Rate of VGPR or better was higher in patients with t(11;14) and/or cyclin D1 overexpression (83% vs 60%; P=0.55). Of the 4 patients who received venetoclax and statins for t(11;14) disease, 3 had CR and 1 had VGPR. One renal and 3 cardiac responses were observed. At last follow-up, 2 patients with VGPR had died while the rest had ongoing responses. Conclusions: In our study, most patients had t(11;14) and progressed on dara within 20 weeks. Salvage therapy incorporating novel agents yielded impressive responses. The combination of venetoclax and statins was effective in overcoming the negative impact of t(11;14) although further studies are needed for validation.[Table: see text]
Prevalence of monoclonal gammopathy of undetermined significance in black South African men.
Authors: Cicero Kara Ilene , Joffe Maureen , Patel Moosa , Pentz Audrey , Ruff Paul , Lentzsch Suzanne , Leng Siyang , Chiuzan Codruta , Jacobson Judith , Rebbeck Timothy , Neugut Alfred I. 
Published: June 2022

e20032 Background: Monoclonal gammopathy of undetermined significance (MGUS) is the precursor to multiple myeloma (MM). MM disproportionately affects black individuals, but the cumulative risk of progression from MGUS to malignancy does not differ by race. Hence, the racial disparities in MM incidence appear to arise from differences in the occurrence of MGUS. Nonetheless, MGUS has been studied mainly in white populations; the study that first described the natural history of MGUS was conducted by Kyle, et al. (2006) in 97.3% white Olmsted County, Minnesota. Methods: We determined the prevalence of MGUS among black South African men >30 years of age at the Chris Hani Baragwanath Academic Hospital in Johannesburg. We conducted serum protein electrophoresis (SPEP) and free light chain (FLC) quantification and used the same criteria for MGUS as the Olmsted County studies: a monoclonal protein on SPEP or an abnormal FLC-ratio plus elevation in the appropriate FLC. We also investigated the association between MGUS and various clinical and behavioral factors. Results: The prevalence of MGUS in our cohort (n=386) was 8.03% (95%CI 5.32-10.74), nearly 1.6-fold higher than in Olmsted County males. In a univariable logistic regression model, MGUS was associated with HIV status (odds ratio (OR) 2.39, 95%CI 0.95-5.51), but in the adjusted model that also included body mass index (BMI) and cigarette use, the magnitude of the association decreased to an OR of 2.17 and was not statistically significant. MGUS was associated with current (vs. never) cigarette smoking in both univariable (OR 5.2, 95%CI 1.53-24.0) and multivariable (OR 4.11, 95%CI 1.08-20.4) models. Conclusions: Not only did we find the prevalence of MGUS in black South African men to be substantially higher than in white populations, but we also report that MGUS cases are associated with potentially modifiable risk factors. Building on this pilot study, a larger study is currently underway powered to confirm the relationship between MGUS and HIV, as well as between MGUS and cigarette smoking, in a black African population inclusive of both genders. Future studies designed to evaluate genetic and matched-environmental contributions may elucidate racial disparities and facilitate the development of strategies to prevent plasma cell malignancies.[Table: see text]
Real-world treatment patterns and clinical outcomes in early stage non-small cell lung cancer (eNSCLC) in Canada.
Authors: O'Sullivan Dylan E , Boyne Devon J , Ford-Sahibzada Chelsea , Inskip Jessica A , Smith Christopher J , Sripada Kaushik , Brenner Darren R , Cheung Winson Y 
Published: June 2022

e20504 Background: The prognosis of eNSCLC remains uniformly poor. An understanding of current therapies and outcomes can provide insights into how novel therapies can be integrated into our management paradigm. Methods: We conducted a large, retrospective, population-based cohort study of de novo eNSCLC patients (stages IB, IIA, IIB, and IIIA) diagnosed in Alberta, Canada between 2010-2019 using electronic medical records and administrative claims data. The primary objectives were to describe treatment patterns and survival outcomes among eNSCLC patients. In addition, we examined the association between systemic therapy (ST) and overall survival (OS) using multivariable Cox proportional hazards models. Results: A total of 5,126 eNSCLC patients were included. The stage distributions were: 31.0% IB, 13.4% IIA, 17.7% IIB, and 37.9% IIIA. The mean (SD) age was 71.3 (10.3) years and 52.5% were female. 45.3% of patients were referred to a medical oncologist, ranging from 23.7% in stage IB and 58.3% of IIIA. Among stage IB and II patients, 59.2% and 58.1% received surgery, respectively, while 25.7% of stage IIIA patients underwent surgery. 23.6% of patients initiated ST, ranging from 3.5% in stage IB to 38.5% in IIIA. ST use increased over the study period by 9.3% and 19.5% in stage IIB and IIIA disease, respectively. Median follow-up for the cohort was 21.86 months; median OS was 28.18 months (95% CI: 26.56-29.69). Median OS for stage IB, IIA, IIB, and IIIA were 49.01 (95% CI: 45.00-54.15), 36.56 (95% CI: 32.94-42.25), 29.23 (95% CI: 25.32-33.11), and 16.50 (95% CI: 15.39-17.59). Findings from the Cox analyses are tabulated (see Table). For stage IIB and IIIA individuals who received surgery, adjuvant ST was also associated with a decreased likelihood of death [hazard ratios (HR) of 0.77 (95% CI: 0.56-1.07) and 0.69 (95% CI: 0.54-0.89), respectively]. Conclusions: In a Canadian real-world setting, stage IIB and IIIA patients who received adjuvant ST tended to have better survival than patients who did not. However, a considerable proportion of patients are not referred to a medical oncologist to be considered for ST. Improving referral pathways appears to be an essential step to ensure that emerging novel therapies are implemented effectively in the real world so that potential survival gains from new drugs can be realized.[Table: see text]
Physician referral patterns and use of adjuvant therapy among stage IB-IIIA non-small cell lung cancer (NSCLC) patients (2010-2017).
Authors: Kale Hrishikesh , Wang Wei-Jhih , Chirikov Viktor , Shah Anne , Apple Jon 
Published: June 2022

e20509 Background: As the treatment landscape for early-stage NSCLC continues to evolve with the recent approvals of targeted and immunotherapy agents in the adjuvant setting, it is important to understand physician referral patterns and predictors of adjuvant therapy (AT). This study examined physician referral patterns at key treatment phases and assessed predictors of receiving AT in stages IB-IIIA NSCLC patients. Methods: A retrospective study using the linked SEER-Medicare database (01/01/2010-12/31/2017) included patients newly diagnosed with stages IB-IIIA NSCLC who received surgical resection. Specialties were identified by linking NSCLC claims to the AMA Physician Masterfile. AT was defined as the use of systemic chemotherapy or radiation therapy within 4 months of surgery. Multivariable logistic regression was conducted to assess predictors of receiving AT. Results: A total of 7,108 patients met the study criteria (53% IB; 9% IIA; 19% IIB; 20% IIIA). Primary care physicians (PCP) (71%), surgical oncologists (29%), and medical oncologists (36%) were the most frequently visited first specialists during pre-diagnosis, diagnosis to surgery, and post-surgery phases, respectively. The median time from diagnosis to surgery was 44 days. After surgery, 74% patients visited a medical oncologist (62% IB; 87% IIA; 83% IIB; 88% IIIA). About 41% received AT (21% IB; 64% IIA; 56% IIB; 69% IIIA). Of those, the median time from surgery to adjuvant therapy was 46 days. In the adjusted analysis, later stage at diagnosis and shorter referral time to medical oncologist had the highest odds of receiving AT (Table). Conclusions: The strongest predictors of receiving adjuvant therapy were time to medical oncologist post-surgery and stage at diagnosis. Future studies in the era of targeted therapies can use these results as a benchmark to optimize management and outcomes as well as assess changes in referral patterns in IB-IIIA NSCLC patients.[Table: see text]