bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional activity of peripheral blood mononuclear cells in patients with non-Hodgkin's lymphomas receiving treatment after COVID-19 disease.
Authors: Sagakyants Aleksandr B. , Lysenko Irina B. , Shulgina Oksana G. , Kamaeva Inna A. , Zolotareva Ekaterina I. , Novikova Inna A. , Vladimirova Liubov Yu , Kit Oleg I. , Dzhenkova Elena A. , Zlatnik Elena Yu , Dmitrieva Viktoria V. , Nikolaeva Nadezhda V. 
Published: June 2022

e19564 Background: Patients with non-Hodgkin's lymphomas (NHL) develop abnormalities in the structural and functional organization of the immune system leading to immune deficiency. Chemotherapy (CT) in patients after SARS-CoV infection is associated with a more severe disease course affecting the treatment results. The cytokine-producing activity (CPA) of blood cells is poorly studied, while it determines the effectiveness of antitumor and anti-infective functions of the immune system. The purpose of this study was to evaluate CPA of peripheral blood mononuclear cells in patients receiving treatment for NHL after COVID-19. Methods: The study included 8 patients with large B-cell NHL with PCR-confirmed COVID-19 infection in past medical history. All patients received from 3 to 4 chemotherapy cycles. K2EDTA blood samples obtained before and after 3-4 CT cycles were divided into 2 parts after dilution with a sterile nutrient medium solution: part 1, to assess spontaneous CPA; part 2, with addition of a sterile mitogen (phytohemagglutinin 4 μg, concanavalin A 4 μg, and lipopolysaccharide 2 μg) to assess stimulated CPA. The samples were incubated for 24 hours at 370C, and the levels of IL-1β, IL-6, IL-8, IL-10, IL-18, IL-4, IL-2, TNF- α, INF-ɣ, INF-α were determined in the obtained plasma. The stimulation coefficient (SC) was calculated as the ratio of stimulated CPA to spontaneous CPA. Results: 3-4 CT cycles in patients after COVID-19 was accompanied by an elevation of spontaneous CPA of the blood cells IL-6, INF-ɣ, TNF-α, IL-8, compared to the initial levels, by 678%, 127%, 64% and 57%, respectively. The ability of cells to spontaneous production of IL-10 and INF-α decreased by 30% and 100%. The mitogen-induced CPA of mononuclear cells in relation to IL-10, IL-6, IL-2, IL-1β and INF-α increased by 300%, 130%, 92%, 52% and 52%, respectively. Stimulated CPA in relation to INF-ɣ decreased by 21% compared to initial levels. As a result of the revealed CPA changes, SC in NHL patients after COVID-19 receiving CT increased, compared to the initial levels, by 465%, 92% and 48% respectively for IL-10, IL-2, IL-1β, as well as the appearing ability to INF-α production. SC for IL-6, INF-ɣ, TNF-α, and IL-8 decreased by 70%, 66%, 33% and 27% respectively. Conclusions: Certain features of spontaneous and mitogen-activated CPA of blood mononuclear cells were revealed in NHL patients after COVID-19, indicating a change in the functional activity of immune cells which could affect the development of the disease and the effectiveness of the therapy. The data obtained require additional studies and can be used to assess the condition of patients, as well as to predict the therapy efficacy.
Clinical efficacy of daratumumab (DARA)-based second line therapy after DARA-containing and DARA-free induction therapies in multiple myeloma: A single center experience.
Authors: Ciardiello Amanda , Korde Neha , Hultcrantz Malin , Hassoun Hani , Mailankody Sham , Shah Urvi A , Lu Sydney X. , Patel Dhwani , Maclachlan Kylee , Lahoud Oscar Boutros , Shah Gunjan L. , Scordo Michael , Chung David J. , Landau Heather Jolie , Giralt Sergio , Derkach Andriy , Usmani Saad Zafar , Lesokhin Alexander M. , Tan Carlyn Rose Co 
Published: June 2022

e20005 Background: DARA has been FDA approved for newly diagnosed multiple myeloma (NDMM) in combination with lenalidomide/dexamethasone (Rd), bortezomib/melphalan/dex, and bortezomib/thalidomide/dex since 2018. With the increase use of DARA combinations in NDMM, understanding the role of DARA retreatment at relapse needs to be examined in clinical practice. Herein, we describe a single institution experience of the efficacy of DARA-based retreatment as second line of therapy (LOT2) for patients (pts) who received DARA-based induction compared to DARA-free induction regimens. Methods: Thirty-three pts treated with DARA-based LOT2 at MSK from 1/2015 to 9/2021 were included in this retrospective analysis. Primary endpoint was overall response rate (ORR; ≥PR by IMWG criteria). Discrete patient characteristics were summarized by frequency (percentage) and continuous characteristics were summarized by median (IQR). Progression free survival (PFS) was evaluated by Kaplan-Meier method. Results: Two cohorts were identified based on prior DARA exposure: cohort 1 (N=6) received DARA-based induction without meeting DARA-refractory criteria and cohort 2 (N=27) had carfilzomib and Rd (KRd) induction (Table). Median follow-up was 13.8 and 14.5 months for cohorts 1 and 2, respectively. In cohort 1, 5 pts received DARA-KRd and 1 had DRd as first line therapy (LOT1). Median time between last dose of DARA in LOT1 and first dose of DARA in LOT2 was 17.5 months (IQR 12.1-19.8). ORR were 83% and 79% for cohorts 1 and 2, respectively. In cohort 1, ORR comprised of 1 sCR, 1 VGPR, and 3 PR. For cohort 2, there were 5 sCR/CR, 7 VGPR, and 9 PR. Median PFS was not reached in cohort 1 and 16.2 months in cohort 2. Conclusions: In a cohort of pts retreated with DARA after DARA-based induction, our findings suggest that DARA-exposed MM pts may derive benefit from DARA retreatment in subsequent lines of therapy similarly to pts who were DARA-naïve prior to DARA-based LOT2. Longer follow-up is needed to assess survival outcomes. In addition, larger confirmatory studies are warranted to further characterize response characteristics of DARA combinations in LOT2, especially as DARA-based therapy is increasingly used in treating NDMM. [Table: see text]
T-cell redirected bispecific antibodies in relapsed and refractory multiple myeloma: A systematic review and meta-analysis.
Authors: Waqar Syed Hamza Bin , Khanam Razwana , Rehman Mohammad Ebad Ur , Chattaraj Asmi , Ali Hassam , Anwer Faiz 
Published: June 2022

e20014 Background: Multiple myeloma (MM) is a malignant plasma cell disorder which remains incurable, and in relapsed and refractory treatment, chimeric antigen receptor therapy shows promise. Bispecific antibodies (bsAbs) utilize the exact mechanism by engaging BCMA and other potential tumor-associated antigens on myeloma cells and T-cells. We have conducted a systematic review and meta-analysis to evaluate the efficacy and safety of bsAbs in heavily pretreated MM cohorts. Methods: We searched PubMed, Clinicaltrials.gov, Cochrane, Google Scholar, Embase, and major conferences (oral and poster presentation), with MeSH terms and keywords for “multiple myeloma” or “relapsed refractory multiple myeloma,” AND “bispecific antibody” or “BiTE”. We included all original studies reported in the English language published from inception until January 2022. After primary and secondary screening, eleven clinical trials were included. Pooled analysis was done with the help of random effects model (Freeman-Tukey Double Arcsine Transformation) in OpenMetaAnalyst software. Results: We identified nine phase I and two phase II trials (n=837), with a mean age of 64.5 years. Most cohorts being triple-, quad- or penta-refractory MM. Complete response (CR) or stringent CR (sCR) reported is 12% (95% CI 9-15.3%, I² 16.54%, n=66), very good partial response (VGPR) 14.8% (95% CI 8.3-22.7%, I² 80.57%, n=93) and partial response (PR) 11.8% (95% CI 0.2-3.41%, I² 93.21%, n=26). The overall response rate (ORR) reported is 59.5% (95% CI 44.7-73.5%, I² 90.71%, n=307). Among the most common adverse events anemia is seen in 44.2% (95% CI 38.1-50.4%, I² 17.86%, n=152), neutropenia in 33.8% (95% CI 18.4-51.2%, I² 93.27%, n=179), thrombocytopenia in 32% (95% CI 21.4-43.6%, I² 75.96%, n=113) and cytokine release syndrome in 57.1% (95% CI 45.5-68.4%, I² 85.63%, n=315). Conclusions: Bispecific antibodies have shown promising efficacy in relapsed and refractory MM cohorts with a very well safety profile. Upcoming phase II/III trials are much awaited, along with combination studies of bsAbs with other agents to gauge response.[Table: see text]
COVID-19 impact on multiple myeloma prescribing patterns.
Authors: Pittos Elias , Shah Dipti , McAuliff Kelly , McCarthy Amanda , Cavers William , Grover Rashmi , Feczko Lucia , Avalos-Reyes Elisea , Johnson Kjel Andrew 
Published: June 2022

e20027 Background: COVID-19 has impacted several areas of oncology patient care, most notably the reduction of patient visits for treatments. Standard treatment of multiple myeloma (MM) involves a combination of intravenous (IV) and oral therapies. The purpose of this study is to assess the impact COVID-19 had on IV and oral medication prescribing patterns pre and during the COVID-19 pandemic among MM patients. Methods: This is a retrospective review of adult MM patients insured by a large commercial and Medicare health plan in the United States who started a new IV or oral MM agent during the study period. To assess the impact of COVID-19 on IV and oral medication prescribing patterns, we compareda pre-COVID period (March 1-August 31, 2019) to a COVID period (March 1-August 31, 2020). We utilized medical and pharmacy claims to identify patients and calculated new therapy starts per newly diagnosed patient (defined as the number of patients starting a new IV or oral medication for MM divided by the total number of patients with a first indication date of MM within the study timeframe). We compared rates using a Chi-square test; p-values ≤ 0.05 were considered statistically significant. Results: 1,754 patients were enrolled in the study; there were no significant differences in demographic characteristics pre and during COVID-19 between the two groups with respect to age (67.05 vs. 66.64; p=0.45), gender (p=0.80), insurance plan type (p=0.17), geographical region (p=0.26) and medication (p=0.59). During COVID-19, the number of newly diagnosed MM patients decreased by 22% (9,657 to 7,560) and the total number of new therapy starts decreased by 11% (930 to 824). When looking at rates of new therapy starts per newly diagnosed patient, both IV (11%; p=0.03) and oral (51%; p=0.03) medication rates significantly increased. Additionally, there were significant increases in new therapy start rates by region in the Northeast for oral (157%; p<0.01) and West for IV (32%; p=0.02) medications. There were no significant differences in new start rates by insurance plan type (all p>0.08). Conclusions: While the total count of new therapy starts, a proxy for new diagnoses, decreased during COVID-19, the rate of new starts for both IV and oral therapies for patients diagnosed with MM significantly increased. These increased start rates may be explained by a remarkable 22% drop in the total number of newly diagnosed MM patients during COVID-19. As the pandemic continues, further study is warranted to understand how COVID-19 may impact IV vs. oral usage in MM. [Table: see text]
A novel parameter reflecting the interaction between CD8+ T cells and cancer-associated fibroblasts.
Authors: Zheng Xinlong , Xiao Weijin , Zeng Dongqiang , Peng Wenying , Long Feng , Jiang Kan , Bai Jing , Zheng Xiaobin , Miao Qian , Mok Tony S. K. , Lin Gen 
Published: June 2022

e20536 Background: Accumulating evidence reveal complicated crosstalk amongst cancer-related fibroblasts (CAFs) and immune cells in tumor microenvironment (TME). However, interaction within CAFs and immune cells, and their relationship with clinical outcomes remain largely undetermined. Methods: Interaction between CAFs and immune cells was evaluated by the CD8+ T cells/CAFs ratio (CFR), denoting great difference within single-sample gene-set enrichment analysis (ssGSEA) scores. Association of CFR with survival was examined in TCGA/GEO lung cancer and TCGA pan-cancer cohorts. Correlation between CFR and immunotherapeutic efficacy was determined in five independent cohorts including melanoma, lung cancer and urothelial cancer. orrelations between CFR and objective response rates (ORR) reported in the literature following pembrolizumab monotherapy were calculated in 20 TCGA cancer cohorts. To translate the in silico findings into clinical use, immunohistochemically-detected CD8/α-SMA ratio was used as prognostic and immuno-therapeutically predictive biomarker in two lung cancer cohorts. Furthermore, correlation within CFR, TMB, PD-L1, and molecular/genomic characteristics of CFR subgroups was also evaluated. Results: A moderately positive correlation existed between CAFs and immune cells infiltration in various cancer types. Higher immune cells/CAFs ratios indicated favorable prognosis regardless of distinct immune cells. Higher CFR, an independent risk factor and complementary factor to PD-L1 and TMB, was strongly associated with improved survival in melanoma, lung cancer and urothelial cancer immunotherapy cohorts (log-rank test, P < 0.05). Moreover, CFR averages across cancer types provided a higher correlation coefficient with the ORR following pembrolizumab monotherapy when compared to PD-L1 expression and TMB, r = 0.65 versus 0.36 and 0.31, respectively. Finally, in the clinical setting, CD8/α-SMA ratio was validated as an independent prognostic and predictive biomarker of immunotherapy efficacy in non-small cell lung cancer (HR, 0.21, 95% CI, 0.12-0.37, P < 0.001; HR, 0.37; 95% CI, 0.19-0.75; P < 0.001). Low CFR was associated with upregulation of hypoxia, TGF-β signaling, epithelial-mesenchymal transition and angiogenesis. Conclusions: CFR was a promising biomarker in the prediction of immunotherapeutic efficacy across various malignancies.
Predictive value of the biomarker of peripheral blood of lung carcinoma patients responding to PD-1 treatment: A real-word study.
Authors: Su Shu , Lv Xin , Chen Fangjun , Qi Liang , Ren Wei , Yu Lixia , Yang Xiaoyan , Yan Tingting , Li Shanping , Wei Jia , Liu Baorui , Wang Lifeng 
Published: June 2022

e20549 Background: The introduction of anti-PD-1 antibody has greatly improved the clinical outcomes of patients with lung cancer. Pre-treatment biomarkers in peripheral blood such as neutrophil-lymphocyte ratio, cytokine level, or clinical features such as BMI, lactate dehydrogenase, and prognostic nutrition index have been shown to be predictive markers treated by immunotherapy. Here we retrospectively analyzed the efficacy of PD-1 antibody-based therapy in patients with locally advanced un-operable or metastatic lung cancer patients and report an association between peripheral blood biomarkers with clinical response in these patients. Methods: We conducted a single-center study by including medical record data for lung cancer patients treated with PD-1 antibody first-line or posterior-line either as monotherapy or in combination with chemotherapy. The patients enrolled from March 2020 to December 2021 were treated with albumin paclitaxel or pemetrexed plus carboplatin、lobaplatin or cisplatin combined with PD-1 antibody. The clinical response were assessed after 2 circles of therapy. Peripheral blood were drawn prior to therapy and post therapy. Multiple Th1 and Th2 cytokines levels in the blood serum were evaluated and phenotype of T cells of peripheral blood were also analyzed. The association between cytokines levels, T cells phenotype and clinical response were investigated. Results: 61 patients with stage IIIA-IV lung cancer were enrolled in the study. 40 non-squamous NSCLC patients, 15 Squamous NSCLC patients and 6 SCLC patients received PD-1 antibody with chemotherapy. 40(65.6%)patients were first-line therapy and 21(34.4%) were posterior-line treatment. 42(68.9%) patients achieved partial response(PR), 7 (11.5%) patients were stable(SD) and 12(19.6%) patients had progressed disease (PD). The disease control rare(DCR) was 80.4%. In DCR group, higher levels of IFN-γ(P = 0.023,P < 0.05), TNF-α(P = 0.007,P < 0.05)and IL-5 (P = 0.002, P < 0.005) were detected in peripheral blood prior to the treatment comparing to PD group. Besides, the reduction of lymphocyte absolute counts in peripheral blood after PD-1 antibody-based therapy was associated with disease progression(P = 0.023,P < 0.05). Furthermore, higher CD8+CD27+T cells in peripheral blood before therapy was associated with worse clinical response(P = 0.019,P < 0.05) and higher ratio of CD4+CD45RO+CD62L+/ CD4+CD45RO+CD62L-seems to related with better clinical response, though without statistic difference due to limited sample size. Conclusions: These results suggest for the first time that serum IFN-γ, TNF-α and IL-5 levels could predict clinical efficacy with anti-PD-1 blockade therapy in lung cancer patients. Other biomarkers include lymphocyte counts or phenotype may also have predictive value. Large prospective studies need to further clarify the value of these biomarkers.
Immune-related gene set prediction model contributes to the evaluation of prognosis in lung adenocarcinoma patients.
Authors: Zhang Liwen , Liu Yang , Lu Leilei , You Dong 
Published: June 2022

e20550 Background: In recent years, rapid progress of immunotherapy (I/O therapy) development brings new hope to LUAD patients. The subtypes and/or quantality of TIL-IC cells were closely related to the prognosis and to the I/O therapy’s response in patients with a variety of solid tumors. In order to stratify high-risk and low-risk LUAD patients, we herein established a prognostic prediction model based on the expression of large-scale immune infiltration genes in LUAD patients. Methods: RNA sequencing data and relevant clinical information of LUAD patients ( n = 501) were obtained from the TCGA cohort. Stromal and immune scores were calculated using ESTIMATE algorithm. The differentially expressed immune-related genes (IRGs) were identified using the “DESeq2” package in R platform. Patients were randomly divided into training set and validation set with a ratio of 8:2. Univariate and Lasso Cox regression analyses were performed to identify overall survival (OS)-related IRGs. Next, stepwise multivariate Cox regression analysis was carried out to establish an optimal risk model of immune-related prognostic gene sets in the training cohort. Kaplan-Meier curves and receiver operating characteristic (ROC) curves were used to examine the predictive performance of the model in the validation cohort. Results: A total of 643 IRGs were identified in these LUAD patients, of which 140 IRGs were significantly associated with OS by univariate Cox regression analysis (P < 0.05). Lasso Cox and stepwise multivariate Cox regression analysis identified IRGs as independent prognostic factors, including C20orf197, SPRR1B, CHRNA5, SLC14A2, RP11-284F21.9, IGLV9-49, IGF2BP1, and C5orf64. The final immune-related gene set model was as follow: risk score = −0.13 * expression level of C20orf197 + 0.074 * expression level of SPRR1B + 0.23 * expression level of CHRNA5 − 0.11 * expression level of SLC14A2 + 0.11 * expression level of RP11-284F21.9 - 0.076 * expression level of IGLV9-49 + 0.048 * expression level of IGF2BP1 - 0.42 * expression level of C5orf64. Patients were divided into high-risk group and low-risk group with the median risk score. Kaplan–Meier survival analysis showed that the high-risk group had a significantly poor prognosis, when compared to the low-risk group in the training set ( HR 2.77, 95%CI; [1.96 - 3.93], P < 0.0001). The ROC curve analysis equally revealed that the area under curves for OS in the first and fifth year were 0.82 and 0.81, respectively, in the validation cohort. Taken together, the eight IRGs risk prediction model could effectively stratify LUAD patients according to prognosis. Conclusions: We constructed a prognostic prediction model for LUAD patients, which consisted of a robust signature of eight IRGs. This model could effectively stratify high-risk and low-risk LUAD patients and help to customize personalized treatment plans.
Influence of ancestry in racial disparities of squamous cell lung cancer.
Authors: Choi David , Lee Michelle Jeung-Eun , Jain Sanjay R. 
Published: June 2022

e20554 Background: Significant progress has been made in the screening, diagnosis, and treatment of squamous cell carcinomas of the lung (LUSC). Despite the advancements, African American populations continue to experience worse disease burden and poorer overall survival, even after controlling for patient and tumor characteristics. While the interplay of various social determinants of health is well known to contribute to racial disparities in cancers, the molecular basis of racial disparity is less understood. Given the diversity of the US population that comprise of genetically admixed groups, understanding the role of ancestry and its influence on biology of cancers that drive incidence and prognosis is paramount to reducing racial disparities. Therefore, in this study, we aimed to investigate the influence of African (AFR) ancestry in genetic mutations of LUSC. Methods: We utilized The Cancer Genome Ancestry Atlas (TCGAA) to obtain data on the genetic ancestry and ancestral composition of 504 LUSC patients. The dataset contained 459 self-reported whites, 32 blacks, and 11 Asians. The percentage of each patient’s ancestral composition (European, AFR, Asian, and Native American) was revealed via the LAMP technique. The dominant ancestry was defined as those with genetic composition of ≥50% from one of four ancestral backgrounds. Genetic alteration profiles and clinical data of patients were obtained from LUSC TCGA PanCancer Atlas through GDC data portal. Of those with AFR dominant ancestry, we analyzed the differences in the gene mutation frequency based upon the proportion of AFR ancestry. Results: Ancestry analysis uncovered 30 AFR ancestry dominant cases with a mean AFR composition of 78.4%. We found 14 subjects with > 80% AFR ancestry and 16 subjects with 50-80% AFR ancestry. Two patients from the > 80% were excluded from the mutational analyses due to absence of genetic profiles in the data portal. TP53 was the most frequently mutated gene with a rate of 91.7% and 87.5% in > 80% and 50-80% AFR groups, respectively. Evaluation of the classic genetic mutations that drive disease pathology in LUSC (EGFR, ALK, PIK3CA, NRAS, KRAS) revealed 25% of > 80% AFR ancestry subjects carried mutations in at least one of these genes compared to 6.3% in the 50-80% AFR ancestry subjects. Also, a trend towards worse overall survival (OS) was seen in those with greater proportion of AFR ancestry (median OS of 27.2 months in > 80% group vs 43.9 months in 50-80% group). Conclusions: Despite the limited sample size, our study highlights substantial heterogeneity in tumor biology even within those of AFR ancestry and that genetic ancestry may impact tumor and host biology that contribute to disparities. Moving forward, engagement of the African American community into clinical trials and genomic studies are needed to explore ancestral influence on tumorigenesis, and to facilitate discovery of new actionable targets to help eradicate racial disparities in lung cancer.