bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contemporary real-world associations between performance status and clinical outcomes in patients with cancer: A retrospective cohort study.
Authors: Kumar Deepika , Neeman Elad , Zhu Shiyun , Sun Hongxin , Kotak Dinesh , Liu Raymond 
Published: June 2022

6578 Background: The ECOG-PS (Eastern Cooperative Oncology Group Performance Status) scale is often used to guide cancer care, but the degree to which it predicts contemporary real-world clinical outcomes, in general and within certain patient groups, is relatively unknown. This retrospective cohort study examined associations between ECOG-PS levels and adverse outcomes in cancer patients with diverse patient characteristics. Methods: Various patient characteristics and nurse-rated ECOG-PS scores (range: 0-4) were recorded for all 21,730 adult patients with cancer receiving intravenous systemic therapy between 01/01/2017 and 12/31/2019 at 18 Kaiser Permanente Northern California cancer centers. Differences in baseline characteristics by ECOG-PS scores were evaluated using chi-square tests for categorical variables and ANOVA for continuous variables. Univariable and multivariable Cox Proportional Hazard models were used to test the ability of ECOG-PS to predict the occurrence of adverse clinical outcomes, including 1-month emergency department (ED) visits and hospitalizations, and 6-month mortality. Results: Overall, 42.5% of patients had ECOG-PS = 0, 42.5% had ECOG-PS = 1, 10.5% had ECOG-PS = 2, 4% had ECOG-PS = 3 and 0.4% had ECOG-PS = 4. Most patients were women (58%), non-Hispanic White (61%), English speakers (93%) and married/domestic partners (63%). African Americans, men, older patients, and those with higher Charlson comorbidity index or Stage IV cancer were found to have higher ECOG-PS levels (all p < 0.001). In multivariable analysis, ECOG-PS of 3-4 were associated with higher ED visits (HR 3.85, 95% CI [3.47-4.26]), hospitalizations (HR 4.7, [4.12-5.36]) and mortality (HR 7.34, [6.64-8.11]), compared with ECOG-PS = 0. Upper gastrointestinal (GI) and Stage IV cancers were associated with a higher risk of ED (upper GI: HR 2.39, [2.12-2.68], (stage IV: HR 1.31, [1.21-1.42]), hospitalization (HR 2.67, [2.27-3.13], (HR 1.51, [1.35-1.68]), and mortality rates (HR 3.37, [2.97-3.81], (HR 1.82, [1.68-1.98]), compared to Breast and Stage I cancers; however, advanced age was not associated with these outcomes. Interactions between ECOG-PS and cancer type as well as ECOG-PS and age group were statistically significant (p < 0.001), such that ECOG-PS was more predictive of adverse outcomes in younger patients and those with breast cancer. Conclusions: In this contemporary real-world cohort, multivariable analysis showed that ECOG-PS, cancer type and stage were strong predictors of ED visits, hospitalizations and mortality; however, advanced age was not. These results also show that ECOG-PS is more predictive of clinical outcomes in certain patient groups. Our findings may have implications on the use of ECOG-PS for clinical decision making.
Oncologist consideration of patient health insurance coverage and out-of-pocket costs for genomic testing in treatment decision.
Authors: Shi Kewei , Yabroff K. Robin , Zhao Jingxuan , De Moor Janet , Freedman Andrew , Zheng Zhiyuan , Nogueira Leticia M. , Han Xuesong , Klabunde Carrie N. 
Published: June 2022

6600 Background: Use of genomic testing, especially multi-marker tumor panels, is increasing in the United States. Not all tests and related treatments are covered by health insurance, which can result in substantial patient out-of-pocket (OOP) costs. Although most patients are concerned about OOP costs, little is known about oncologists’ treatment decisions with respect to patient health insurance coverage and OOP costs for genomic testing. Methods: We identified 1,049 oncologists who reported using multi-marker tumor panels from the 2017 National Survey of Precision Medicine in Cancer Treatment. Separate multivariable ordinal logistic regression analyses were used to assess the associations of oncologist, practice, and patient characteristics and the oncologist ratings of the importance of health insurance coverage and OOP cost for genomic testing as part of treatment decisions. Results: Among oncologists, 47.3%, 32.7% and 20.0% reported that patient insurance coverage for genomic testing was very important, somewhat important, and a little/not important, respectively, in treatment decisions. 56.9%, 28.0%, and 15.2% reported patient OOP costs for genomic testing were very, somewhat, or a little/not important in treatment decisions, respectively. In adjusted ordinal logistic regression analyses, oncologists who used next-generation gene sequencing tests were more likely to report patient health insurance and OOP costs for testing as important (odds ratio (OR) = 2.0; 95% confidence interval (CI): 1.2, 3.5) and (OR = 2.1; 95%CI: 1.2, 3.7), respectively) in treatment decisions. Oncologists with more years of experience, who treated solid tumors (rather than only hematological cancers), worked in practices without molecular tumor boards for genomic tests, and with higher percentages of patients insured by Medicaid or self-paid/uninsured also reported insurance coverage or OOP costs for testing were important in treatment decisions (all p < 0.05). Conclusions: Physician, practice, and patient characteristics were associated with oncologists’ ratings of the importance of patient health insurance and OOP costs in treatment decisions. Identifying factors that influence physicians’ priorities in treatment decisions may inform the development and targeting of interventions to support patient and physician discussions about oncology care.
Efficacy and safety results from ASCEMBL, a phase 3 study of asciminib versus bosutinib (BOS) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) after ≥2 prior tyrosine kinase inhibitors (TKIs): Week 96 update.
Authors: Rea Delphine , Mauro Michael J. , Hochhaus Andreas , Boquimpani Carla , Lomaia Elza , Voloshin Sergey , Turkina Anna G. , Kim Dong-Wook , Apperley Jane , Cortes Jorge E. , Sasaki Koji , Kapoor Shruti , Allepuz Alex , Quenet Sara , Bédoucha Véronique , Minami Yosuke 
Published: June 2022

7004 Background: Asciminib is the first BCR::ABL1 inhibitor to specifically target the ABL Myristoyl Pocket (STAMP). In the ASCEMBL primary analysis, asciminib had superior efficacy and better safety/tolerability than BOS in pts with CML-CP after ≥2 prior TKIs. After a median follow-up of 2.3 years (16.5 months’ additional follow-up since primary analysis), we report efficacy and safety results (cutoff: October 6, 2021). Methods: Eligible pts were adults with CML-CP after ≥2 prior TKIs, with intolerance or lack of efficacy per 2013 European LeukemiaNet. Pts were randomized 2:1 to asciminib 40 mg twice daily or BOS 500 mg once daily, stratified by major cytogenetic response (MCyR) status (Ph+ metaphases ≤35%) at baseline. The key secondary endpoint was major molecular response (MMR) rate at wk 96. Results: 233 pts were randomized to asciminib (n=157) or BOS (n=76). At cutoff, treatment was ongoing in 84 (53.5%) and 15 (19.7%) pts, respectively; the most common reason for discontinuation was lack of efficacy in 38 (24.2%) and 27 (35.5%) pts, respectively. MMR rate at wk 96 (per ITT) was higher on asciminib (37.6%) than BOS (15.8%). The difference, adjusting for baseline MCyR, was 21.7% (95% CI, 10.5%-33.0%; 2-sided P=.001). More pts on asciminib than BOS, respectively, had BCR::ABL1IS ≤1% (45.1% vs 19.4%) at wk 96. The probability of maintaining MMR and BCR::ABL1IS ≤1% for ≥72 wk was 96.7% (95% CI, 87.4%-99.2%) and 94.6% (95% CI, 86.2%-97.9%), respectively, on asciminib and 92.9% (95% CI, 59.1%-99.0%) and 95.0% (95% CI, 69.5%-99.3%), respectively, on BOS. Median duration of exposure was 103.1 (range, 0.1-201.1) wk on asciminib and 30.5 (range, 1.0-188.3) wk on BOS. Despite the longer duration of asciminib exposure, safety/tolerability of asciminib continued to be better than that of BOS (Table). No new on-treatment deaths were reported since the primary analysis. Most frequent (>10%) grade ≥3 adverse events (AEs) on asciminib vs BOS were thrombocytopenia (22.4%, 9.2%), neutropenia (18.6%, 14.5%), diarrhea (0%, 10.5%), and increased alanine aminotransferase (0.6%, 14.5%). Conclusions: After >2 years of follow-up, asciminib continued to show superior efficacy and better safety/tolerability vs BOS. Responses were durable, with more pts on asciminib in MMR. Additionally, more pts on asciminib had BCR::ABL1IS ≤1%, a milestone response in later lines associated with improved survival. These results continue to support the use of asciminib as a new CML therapy, with the potential to transform standard of care. Clinical trial information: NCT03106779. [Table: see text]
Enrichment of high-risk innate immune cells in Hispanic and Black children with B-acute lymphoblastic leukemia.
Authors: Gilbert Julie R. , Sabnis Himalee S. , Radzievski Roman , Doxie Deon , DeRyckere Deborah , Castellino Sharon M. , Dhodapkar Kavita M. 
Published: June 2022

7021 Background: Black and Hispanic children with B-acute lymphoblastic leukemia (B-ALL) experience worse outcomes compared to their non-Hispanic white (NHW) counterparts. Immune-based therapies have improved the outcomes of children with B-ALL, however, impact of racial/ethnic background on immune microenvironment is less studied. Methods: BM from 61 children with newly diagnosed B-ALL(Hispanic = 21, Black = 17, NHW = 23) was obtained via the Aflac Biorepository. High-dimensional analysis was performed utilizing single cell mass cytometry with 61 markers to characterize T, NK and myeloid cells. Data was analyzed using Cytobank and high-dimensional visualization platforms such as ViSNE. Clinical data including self-reported race/ethnicity and NCI-risk classification were obtained for all samples. Results: Multi-dimensional analysis was carried out for each cell population to dissect race/ethnicity-associated differences. ViSNE clustering of NK cells identified 3 different NK populations, including a distinct population of mature CD57+ NK cells with Tbethi, HLADRhi, granzymeBhi, CD27- phenotype. The distribution of NK subsets was highly impacted by race/ethnicity. Hispanic (H) patients had higher proportions of CD57+ mature NK cells when compared with other groups, (40 ± 4% vs 33 ± 2%; p = 0.03) with pronounced differences apparent within standard risk (SR) patients. H-SR had higher proportion of CD57+ NK cells compared to other SR patients (mean H-SR 43.4 ± 5.87% vs 26.3 ± 2.87% p = 0.0049). ViSNE clustering of myeloid cells identified 5 clusters based on patterns of cell surface markers, including a distinct CD11c+CD16+DRhi inflammatory/non-classical myeloid population. Further analysis showed that NHW-SR patients have significantly lower proportions of CD16+DR+ myeloid cells compared to Hispanic, Black and NHW-HR patients (mean NHW-SR 3.67 ± 2.56% vs Others 10.8 ± 7.87% p = 0.0394). Notably, a phenotypically similar population has recently been implicated in leukemic progression in preclinical models (Witkowski et al, Cancer Cell 2020). In contrast to innate cells, T cell clusters were broadly comparable between different racial/ethnic groups. Conclusions: These studies provide detailed single-cell proteomic analysis and highlight the impact of racial/ethnic background on immune microenvironment in pediatric B-ALL. Our data identify differences in innate immunity with enrichment of high-risk immune-populations in Hispanic and Black children and depletion of inflammatory myeloid populations in NHW-SR children with B-ALL. These variations may contribute to the observed differences in outcomes and may impact application of immune therapies in racial/ethnic groups.
A phase II study of hyper-CVAD with sequential blinatumomab (Blina), with or without inotuzumab ozogamicin (INO), in adults with newly diagnosed B-cell acute lymphoblastic leukemia (ALL).
Authors: Short Nicholas James , Kantarjian Hagop M. , Ravandi Farhad , Yilmaz Musa , Kadia Tapan M. , Thompson Philip A. , Konopleva Marina , Ferrajoli Alessandra , Jain Nitin , Sasaki Koji , Alvarado Valero Yesid , Borthakur Gautam , Dinardo Courtney Denton , Ohanian Maro , Macaron Walid , Garris Rebecca , Zhao Min , Kwari Monica , Loiselle Christopher , Jabbour Elias 
Published: June 2022

7034 Background: Blina and INO are highly effective in relapsed/refractory B-cell ALL and are associated with high rates of measurable residual disease (MRD) clearance. Use of these agents in the frontline setting may improve outcomes. Methods: Patients (pts) 14-59 years of age with newly diagnosed Philadelphia chromosome (Ph)-negative B-cell ALL, including pts who had received no more than 1 prior cycle of chemotherapy, were eligible. Pts received hyper-CVAD alternating with high-dose MTX/Ara-C for up to 4 cycles, followed by 4 cycles of Blina. Pts with CD20+ disease received 8 doses of an anti-CD20 antibody. Eight doses of IT chemotherapy were given. Maintenance was with alternating blocks of POMP (maintenance cycles 1-3, 5-7, 9-11, and 13-15) and Blina (maintenance cycles 4, 8, and 12). Beginning with pt #39, INO at a dose of 0.3 mg/m2 on day 1 and 8 was added to the 2 cycles of MTX/Ara-C and to 2 cycles of Blina (4 total cycles with INO). Results: Characteristics of the 58 treated pts (38 without INO and 20 with INO) are summarized in Table. Among 45 pts with active disease at study entry, 100% achieved CR. Overall, 76% achieved MRD negativity by flow cytometry after induction and 95% at any time over the course of therapy. The median follow-up of the entire cohort is 26 months (range, 3-61+ months). Overall, 5 pts (9%) relapsed, 18 (31%) underwent transplant in first remission (including an additional 2 pts who relapsed post-transplant), 2 (3%) died in CR, and 33 (57%) remain in continuous remission without transplant. All relapses occurred in pts with established poor-risk features and no relapses have occurred beyond 2 years. For the entire cohort, the estimated 3-year OS is 85% and the 3-year continuous remission duration is 84%. No relapses or deaths have occurred in the INO group, and the estimated 1-year OS is 100%. Treatment was overall well-tolerated. One patient discontinued Blina due to recurrent grade 2 neurotoxicity. No pts have discontinued INO due to toxicity and no cases of veno-occlusive disease have been observed. Conclusions: Hyper-CVAD with sequential Blina is highly effective as frontline treatment of Ph-negative B-cell ALL. The addition of INO to this regimen was safe and early results are encouraging, with no relapses observed to date. Clinical trial information: NCT01371630. [Table: see text]
Impact of prior solid tumor on outcomes of allogeneic hematopoietic stem cell transplantation for AML or MDS.
Authors: Albittar Aya , Portuguese Andrew Jay , Gooley Ted , Deeg H Joachim 
Published: June 2022

7048 Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers a definitive treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Prior solid tumor (PST) is felt to portend a worse post-transplant prognosis. The aim of this study was to evaluate the impact of PST history on allo-HSCT outcome. Methods: We retrospectively identified patients with AML or MDS who underwent first allo-HSCT at the Fred Hutchinson Cancer Research Center between 2010 and 2018. Cox regression analysis was used to identify factors associated with mortality among patients with PST, and to compare outcomes of patients with and without PST. Multivariable models were fit, adjusting for cytogenetic risk level, time from PST diagnosis to transplant, receipt of reduced-intensity conditioning (RIC), and age at transplant. Survival estimates were obtained using the Kaplan-Meier method. Results: 1198 patients were included for analysis, of which 101 had a history of PST. After a median follow up of 1301 days among survivors, there was a total of 558 deaths and 322 relapses among all patients. Patients with history of PST were older (62.5 vs 54.9 yrs) and a higher proportion received RIC (52.5% vs 27.3%). The most common PSTs included breast (38/101, 38%), prostate (13/101, 13%), colon (9/101, 9%), thyroid (8/101, 8%), and uterine (7/101, 7%). Among those with known staging (n = 66), stage 1 (28/66, 42%) was the most common, followed by stage 2 (17/66, 26%) then stage 3 (15/66, 23%). The most common therapies provided were surgery (95/101, 95%), cytotoxic chemotherapy (41/101, 41%), radiation (45/101, 45%), and endocrine therapy (25/101, 25%). The unadjusted hazard ratio (HR) of mortality in the PST group relative to the non-PST group was 1.10 (95% confidence interval [CI] 0.83-1.47, p = 0.52). After adjustment for patient age, disease, patient/donor CMV status, KPS, cytogenetic risk, source of stem cells, and donor type, the adjusted HR was 0.91 (95% CI 0.68-1.22, p = 0.59). The unadjusted HR for relapse was 1.15 (95% CI 0.79-1.67, p = 0.48), and adjusted HR was 1.11 (0.76-1.11, p = 0.61). Among patients with PSTs, high-risk cytogenetics were associated with increased mortality (adjusted HR = 2.21; 95% CI 1.16-4.2, p = 0.016) and relapse (adjusted HR = 1.91; 95% CI 1.01-3.60, p = 0.047). Longer time from PST diagnosis to transplant led to a numerically increased mortality in the unadjusted (HR = 1.05; 95% CI 1.00-1.11, p = 0.057) and adjusted (HR = 1.05; 95% CI 1.00-1.11, p = 0.69) models treating time as a continuous linear variable. Conclusions: In our study, a history of PST did not impact overall survival or relapse rate among patients who underwent first allo-HSCT for AML or MDS. As in the overall population, post-transplant outcomes were primarily driven by cytogenetic risk level. However, it is likely that selection of patients with PST for transplantation was biased based on overall risk assessment.
Thrombocytopenic myelofibrosis (MF) patients previously treated with a JAK inhibitor in a phase 3 randomized study of momelotinib (MMB) versus danazol (DAN) [MOMENTUM].
Authors: Gerds Aaron Thomas , Verstovsek Srdan , Vannucchi Alessandro , Al-Ali Haifa Kathrin , Lavie David , Kuykendall Andrew T. , Grosicki Sebastian , Iurlo Alessandra , Goh Yeow Tee , Lazaroiu Mihaela Cornelia , Egyed Miklos , Fox Maria Laura , McLornan Donal P. , Perkins Andrew , Yoon Sung-Soo , Gupta Vikas , Kiladjian Jean-Jacques , Donahue Rafe , Kawashima Jun , Mesa Ruben A. 
Published: June 2022

7061 Background: MMB, an oral JAK1/2 and ACVR1/ALK2 inhibitor, showed clinical activity on MF symptoms, RBC transfusion requirements (anemia), and spleen volume in the SIMPLIFY trials, including in MF patients (pts) with thrombocytopenia. MOMENTUM is a pivotal phase 3 study of symptomatic and anemic MF pts previously treated with a JAK inhibitor (JAKi) testing MMB vs DAN. This analysis evaluated MOMENTUM pts with baseline (BL) platelet counts (PLT) ≤150 x 109/L. Methods: Eligibility: Primary or post-ET/PV MF; DIPSS high risk, Int-2, or Int-1; MF Symptom Assessment Form Total Symptom Score (MFSAF TSS) ≥10; Hgb <10 g/dL; prior JAKi for ≥90 days, or ≥28 days if RBC transfusions ≥4 units in 8 weeks (wks) or Gr 3/4 thrombocytopenia, anemia, or hematoma; palpable spleen ≥5 cm; PLT ≥25 x 109/L. JAKi taper and washout was ≥21 days. Randomization: 2:1 to MMB 200 mg QD plus DAN placebo or DAN 600 mg QD plus MMB placebo for 24 wks. Primary endpoint: TSS response (≥50% reduction from BL) rate at wk 24. Key secondary endpoints, assessed sequentially at wk 24: RBC transfusion independence (TI) rate, splenic response rate (SRR; ≥25% reduction in volume from BL), change from BL in TSS, SRR (≥35% reduction from BL) and rate of zero transfusions since BL. Results: 60 (74%) of 81 MMB pts and 25 (58%) of 43 DAN pts with BL PLT ≤150 x 109/L completed the 24-week randomized treatment (RT) phase. Median BL TSS were 29 (MMB) and 24 (DAN), Hgb were 7.9 (MMB) and 8.0 (DAN) g/dL, and PLT were 67 x 109/L (MMB) and 64 x 109/L (DAN). Prior JAKi was ruxolitinib in 124 pts (100%) and fedratinib in 6 pts (5%). Efficacy results are in Table. These results are consistent with the overall ITT analysis set (N=195). Most common Gr ≥3 TEAEs in the RT phase were thrombocytopenia (MMB, 31%; DAN, 16%) and anemia (MMB, 7%; DAN, 14%); Gr ≥3 bleeding events occurred in 9% of MMB and 5% of DAN pts. TEAEs led to study drug discontinuation in 15% of MMB and 19% of DAN pts in RT phase. A trend toward improved OS up to wk 24 was seen with MMB vs DAN [HR (95% CI)=0.490 (0.195, 1.235)]. Additional analyses of pts with BL PLT <100 x 109/L (N=100) and BL PLT <50 x 109/L (N=31) show similar treatment effects of MMB vs DAN. Conclusions: In thrombocytopenic MF pts who were symptomatic and anemic, MMB was superior to DAN for symptom responses, transfusion requirements, and spleen responses and showed comparable safety and favorable survival. MMB may address a critical unmet need in thrombocytopenic MF pts. Clinical trial information: NCT04173494. [Table: see text]
Racial disparities affecting Black patients with diffuse large B-cell lymphoma.
Authors: Ermann Daniel Arthur , Vardell Victoria , Fitzgerald Lindsey , Shah Harsh , Stephens Deborah Marie , Hu Boyu 
Published: June 2022

7507 Background: Diffuse Large B-cell Lymphoma (DLBCL) is the most common subtype of Non-Hodgkin Lymphoma, with the majority of patients (pts) achieving long-term survival due to the curative nature of frontline therapy. However, limited data exists regarding presentation and clinical outcomes for underrepresented minorities. In this study, we aimed to evaluate the influence of racial identity on overall survival (OS) outcomes for DLBCL pts. Methods: The National Cancer Database was used to identify DLBCL pts diagnosed from 2004-2018. Demographic and treatment characteristics were compared between racial groups. Kaplan-Meier and Cox regression analyses were used to compare OS between Black and white populations. Multivariate analysis and propensity score matching was performed with adjustment for age, stage, co-morbidity score, median income, and insurance status. Results: Of 223,709 DLBCL pts, 87% were white, 8% Black, and 5% other. As compared to white pts at diagnosis, Black pts were younger (mean 56 years [SD ± 16] vs. 66 years [SD ± 15]), more likely to have ≥1 co-morbidity (33% vs. 27%), be HIV-positive (26% vs. 5%), and have both B-symptoms (40% vs. 30%) and stage IV disease (42% vs. 37%) (All p<0.001). In terms of socioeconomic demographics, Black pts were more likely to be uninsured (8% vs. 3%) and be in the lowest median income quartile (43% vs. 15%), but were more likely to receive treatment at academic centers (50% vs. 36%) (all p<0.001). Both Black and white pts had similar IPI scores at diagnosis and were equally likely to receive multi-agent chemotherapy (77% vs. 77%, p<0.001). With a median follow up of 44.9 months, median OS for all treated HIV-negative DLBCL pts was 109 months (range 21-197). Compared to age-matched white pts, Black pts age ≤ 60 had worse median OS (46 vs. 76 months) along with 5- (73% vs. 75%) and 10-year OS (65% vs. 69%) (all p <0.001). Similar results were seen for Black and white pts between the ages of 61-79, but these differences were not demonstrated for pts ≥80 years old (Table). On multivariate analysis, Black race was independently associated with worse OS (HR 1.06, CI 1.01-1.10, p=0.02). Interestingly, the propensity matched analysis demonstrated no significant OS difference between Black and white pts (median 127 vs. 117 months; HR 1.0, CI 0.94-1.06; p=0.90). Conclusions: We present the largest study to date examining racial disparities in DLBCL. This data demonstrates that Black patients have significantly shorter OS compared to white patients, which persists on multivariate analysis. However, this disparity in survival became nonsignificant when patients are equally matched on surrogate markers of healthcare access such as insurance status and median income. Further studies into examining these racial differences are warranted to optimize care for all DLBCL patients. [Table: see text]