bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-line treatment with Bendamustine plus Rituximab for patients with indolent non-Hodgkin’s lymphoma or Mantle cell lymphoma: Real-world experience.
Authors: Kotchetkov Rouslan , Susman David , Gerard Lauren , DiMaria Erica , Nay Derek Wayne 
Published: June 2021

e19540 Background: Bendamustine plus rituximab (B+R) was established as a preferred first line therapy for patients with previously untreated indolent non-Hodgkin’s lymphoma based on the BRIGHT and STIL trials. However, only few reports on efficacy and safety data of this combination in the real-world setting are available to-date. Methods: We conducted a retrospective review of patients who received therapy with standard doses of B+R in our cancer center from June 2013 to January 2021. Patients with indolent non-Hodgkin’s lymphoma (iNHL) and mantle cell lymphoma (MCL) who received more than one cycle of B+R were evaluated. Results: Amongst a total of 201 patients 56% were males and 44% females. Median age at B+R initiation was 72 years (range 34-94). Follicular lymphoma (FL) (50.3%), marginal zone lymphoma (MZL) (19.4%), and lymphoplasmacytic lymphoma (LPL) (14.5%) were the most common iNHL. Stage 3 and 4 diseases represented 19.9% and 68.6% of patients. Extranodal disease was found in 35.8%. The proportion of patients with high risk disease was 48.5% for FL (FLIPI ≥3), 86.6% for LPL (WMISS score ≥2), and 80.5% for MCL (MIPI score ≥6.2). Prior history of secondary malignancy had 23.4% of patients; 11.4% patients had ECOG 3. Most common indications for B+R initiation were bulky symptomatic lymphadenopathy (69.1%), cytopenia (36.8%) and constitutional symptoms (36.8%). Fifty-eight percent of patients had more than one indication for therapy. Median number of B+R cycles delivered was 6 (range: 1-6), median dose of bendamustine was 90 mg/m2 (range 45-90). Full doses of treatment were given in 66.7% of patients, reduced in 33.3% with mean dose 78.3 mg/m2. A total of 50.8% completed 6 cycles with no delays, in 49.2% treatment was delayed (mean delay time 1.8 weeks). Overall response was 94.5%, with 77.6% complete and 16.9% partial remission. Median duration of follow-up was 35 months (range: 4-91). At the end of follow-up, event free survival (EFS) was 77.1% and overall survival (OS) was 79.6%. Six percent of patients relapsed, 8% developed secondary hematological malignancies, including 14 cases of aggressive B-cell lymphoma and 2 cases of MDS. 16.9% of patients required support with G-CSF. Grade 3-4 neutropenia was recorded in 22.4%, febrile neutropenia in 7.5%, grade 3-4 anemia in 7.9%, and grade 3-4 thrombocytopenia in 3.9% of patients. Rituximab-associated infusion reactions, skin rash, thrombophlebitis, and infection were the most common non-hematological adverse events. A total of 80.6% of patients proceeded to rituximab maintenance. Conclusions: B+R chemoimmunotherapy is feasible to administer in non-clinical trial setting. Despite more dose reduction as compared to STIL trial, B+R retained its efficacy with comparable EFS and OS. No new adverse events or increase in secondary malignancies were found.
Safety of same day HD-MTX with induction therapy for DLBCL with concurrent CNS disease or as prophylaxis for high risk of CNS relapse.
Authors: Barlow Brett , Hatic Haris , Bodine Charles Douglas , Mehta Amitkumar , Goyal Gaurav , Narkhede Mayur 
Published: June 2021

e19545 Background: High-dose methotrexate (HD-MTX) at a dose between 2.5 to 5 gm/m2 is commonly administered in conjunction with standard induction chemotherapy to patients with Diffuse Large B Cell Lymphoma (DLBCL) at high risk of central nervous system (CNS) relapse, as defined by the Lymphoma International Prognostic Index (CNS-IPI). Optimal timing of HD-MTX in relation to induction chemotherapy is unknown. A recent study suggested that HD-MTX intercalated with R-CHOP cycles was associated with increased toxicity and treatment delays without improvement in survival or CNS relapse compared with end of treatment MTX (Wilson et al 2020). This retrospective study evaluates the toxicities and treatment delays associated with HD-MTX administered on day 1 of cycles of chemo-immunotherapy. Methods: This single center retrospective cohort study included 45 patients (pts) with DLBCL with concurrent CNS disease or at high risk of CNS relapse who received HD MTX on day 1 of chemo-immunotherapy at our center. Data was abstracted from chart review and included variables describing clinical and treatment characteristics, time to MTX clearance, toxicities experienced and treatment delays. Results: 31 pts received HD-MTX on the day of R-CHOP chemotherapy, 6 pts received HD-MTX on the day of R-EPOCH (Rituximab, Etoposide, Doxorubicin, Vincristine, Cyclophosphamide, and Prednisone), and 8 pts received HD-MTX with R-MiniCHOP (dose reduced R-CHOP). Same day HD MTX with chemo-immunotherapy was associated with acute kidney injury (AKI; 17-25%), treatment delays >7 days (13-17%), and grade 2 mucositis (11-50%). The burden of toxicities was numerically higher in patients treated with R-EPOCH vs. R-CHOP (Table). Clinical outcomes are summarized in table below. Conclusions: In our heterogeneous population of pts, we describe that the incidence of toxicities and treatment delays experienced with same day HD-MTX are higher with R-EPOCH than with R-CHOP. Comparative studies with intercalated or end of treatment MTX will determine if the incidence of treatment delays, toxicities and de-escalations are higher with same day HD-MTX administration. [Table: see text]
The impact of body weight and body mass index on outcomes of diffuse large B-cell lymphoma treated with axicabtagene ciloleucel.
Authors: Wudhikarn Kitsada , Bansal Radhika , Khurana Arushi , Hathcock Matthew , Bennani N. Nora , Paludo Jonas , Villasboas Jose Caetano , Wang Yucai , Johnston Patrick B. , Ansell Stephen M. , Lin Yi 
Published: June 2021

e19554 Background: Obesity is associated with a pro-inflammatory state and immune dysregulation. Retrospective studies indicate that obesity could affect toxicities and outcomes after immunotherapies including checkpoint inhibitors and allogeneic stem cell transplant. Currently, there are no data specifically on outcomes for obese patients who receive chimeric antigen receptor T (CAR-T) cells. We described the clinical outcome in obese patients with large B cell lymphoma (LBCL) who received axicabtagene ciloleucel (axi-cel). Methods: We analyzed the effect of body weight (BW) and body mass index (BMI) on toxicities and outcomes of 78 adults with LBCL who received axi-cel between June 2016 and October 2020 at Mayo Clinic. Obesity was defined as having BMI of 30 or higher. Results: Of 78 patients, 22 (28%) and 19 (24%) were classified as overweight (BMI 25-29.99 kg/m2) and obese (BMI ≥30 kg/m2), respectively. Baseline characteristics were not statistically significantly different between non-obese and obese patients. The median delivered dose of fludarabine was similar between non-obese and obese patients (89 [0-105] vs 88 [56-94] mg/m2, P=0.32) whereas the median delivered dose of cyclophosphamide was lower in non-obese patients (1503 [1077-1525] vs 1512 [1021-1660] mg/m2, P=0.01). The 30-days cumulative incidence of CRS and ICANS were similar between non-obese and obese patients. BW and BMI were not associated with CRS or ICANS. The overall response rate was 66% (CR 47%) and 68% (CR 53%) in non-obese and obese group, respectively ( P=0.83). The 1-year event free survival (EFS) and overall survival (OS) was 34.6% and 64.5%, neither were different between non-obese and obese patients (EFS 35.8% vs. 30.7%, P=0.60; OS 59.4% vs. 83.9%, P=0.18). The 1-year cumulative incidence of relapse and non-relapse mortality was comparable (60.8% vs. 69.0%, P=0.40 and 3.4% vs. 0%, P=0.42). In the Cox proportional hazards model, higher dose of fludarabine, but not cyclophosphamide, was associated with better EFS and OS; however, neither obesity nor BW were associated with toxicities and outcomes. Conclusions: In our study, Obesity was not associated with risk of toxicities or adverse survival outcomes. The effect of obesity on the pattern of LD chemotherapy dosing including toxicities and outcomes after CAR-T warrants further exploration. [Table: see text]
Prognostic factors of survival in patients with Burkitt lymphoma treated at the National Institute of Neoplastic Diseases in Peru: A 14-years’ experience.
Authors: Solf Rossana , Aliaga Rolig , Vallenas Francisco , Flores Claudio J. , Malpica Luis , Vasquez Chavez Jule Franve 
Published: June 2021

e19570 Background: Burkitt lymphoma (BL) is one of the most aggressive B-cell lymphoma types. However, it has a high cure rate which varies depending on the different clinical pathological characteristics. We aimed to evaluate the prognostic factors for survival in patients with BL. Methods: We performed a retrospective study at the National Institute of Neoplastic Diseases in Peru from 2000 to 2014. We reviewed medical records of patients with BL aged 15 years and above. The data collected were based on clinical characteristics, treatment and survival. Patients with human immunodeficiency virus (HIV) infection were considered for analysis. The overall survival (OS) and progression-free survival (PFS) rates were estimated using the Kaplan-Meier method, the survival curves according to the clinical characteristics were compared using the log-rank test. Prognostic factors were determined using Cox regression modeling. Results: A total of 55 patients had sufficient data for analysis. The median age was 34 years (range 15-73), 78% were male and 73% had B symptoms. Lymph node involvement (LNI) as primary site was present in 89% of patients, of which 43% and 39% were retroperitoneal and cervical LNI, respectively. Bulky mass ( > 10cm) was reported in 73% of the patients. Advanced disease was found in 78% (stage III 31%, IV 47%). Elevated serum LDH level was seen in 60% of cases; and 33% had HIV infection. Intensive chemotherapy was given to 80% (44) of patients, with 34% receiving multi-agent acute lymphoblastic leukemia protocol, 22.8% DA-EPOCH, 18% CODOX-M IVAC, and 11.4% Hyper-CVAD. No patient received rituximab in the front-line setting. The complete response rate was 39%. With a median follow-up of 9 years, the median OS for the entire cohort (N = 55) was 6.9 months (range 1.9-11.9) with a 5-year survival rate of 26.3%. The median OS for the treated patients (N = 44) was 11.3 months (range 3.2-19.4) with a 5-year survival rate of 30.6%. The median PFS was 7.3 months, and the 5-year OFS rate was 30.8%. 5-year OS rates were worse in those with B symptoms (66% vs. 12.5%, p = 0.003), elevated serum LDH level (44.1% vs. 15.2%, p = 0.043), albumin < 3.5 g/dL (36.5% vs. 15.4%, p = 0.023), beta-2 microglobulin > 2.5 mg/L (41.4% vs. 20%, p = 0.029), and HIV infection (31% vs. 16.7%, p = 0.006). In the multivariate analysis, the presence of B symptoms (HR 5.4 [2.2, 13.4], p < 0.001) and HIV infection (HR 2.8 [1.5, 5.4], p = 0.002) were both factors associated with worse survival. Conclusions: In our study, the 5-year OS rate of patients with BL treated with chemotherapy was shorter (30.6%) than in developed countries. The response rates were also lower than in other studies. Inclusion of rituximab is needed to improve response rates. Presence of B symptoms and HIV infection were associated to worse survival.
Clinical characteristics and outcome of mycosis fungoides among children, adolescents, and young adults: Single institution study.
Authors: Taylor Eric , Zhang Yumeng , Hooper Madeline , Seminario-Vidal Lucia , Sokol Lubomir 
Published: June 2021

e19576 Background: Mycosis fungoides (MF) is the most common subtype of cutaneous T cell lymphoma (CTCL) [1]. MF is characterized by the skin infiltrate of small to medium size T lymphocytes with cerebriform nuclei. The incidence of MF increases significantly with age, with a median age at diagnosis of 60 years, and predominantly in white males [2]. The clinical outcome has not been evaluated among children, adolescents, and young adults. This study aimed to evaluate the characteristics and outcomes in this population. Methods: We retrospectively reviewed clinical data on 90 patients with MF at Moffitt Cancer Center between 2000 and 2020. Fifteen patients were diagnosed before the age of 20 years. Our cohort was compared to the largest US epidemiological report by Nath et al. using SEER database, which consists of 4892 patients from 1998-2008 [2]. The Chi-square test was used for comparison. Overall survival (OS) was calculated from diagnosis until death or last contact. OS between different groups was compared using the Kaplan-Meier curve. Hazard ratio and p-value were calculated using the log-rank test. Results: Of 90 patients, the median age at diagnosis was 32 years (range 6-39). The male to female ratio was 1.3:1. White and black races account for 57% and 27% of the patients. Compared to historical control, black patients were significantly higher in the current cohort (27% vs. 13%, p < 0.001). The difference widened in children and adolescents. More patients present with early stage MF in the current cohort (95.6% vs. 83%, p = 0.003). Clinical characteristics, including stage, LDH, WBC, ferritin level, were similar between children/adolescents and young adults. However, our cohort had significantly higher CD8 positive MF, and nearly half of children and adolescents were CD8 positive. Young adults had a higher rate of coexisting skin malignancy; however, this was not statistically significant due to small patient size. Time to diagnosis remained long, especially in children and adolescents’ group. However, the outcome is excellent. At a median follow-up of 4.9 years, four patients deceased, and the median OS was not reached. The prognosis remains poor in patients with advanced disease (HR = 39, p < 0.001) and large cell transformation (LCT) (HR = 8.5, p = 0.009). Conclusions: Compared to historical cohorts, higher proportion of black and female patients were noted in our young cohort with more early-stage and CD8 positive disease. This observation likely represents the different underlying biology of the disease [3]. Clinical outcome in young patients was excellent. However, patients with LCT or advanced stage carry a poor prognosis and need better therapies.
Economic evaluation of six and 12 month (m) treatment with isatuximab and carfilzomib and dexamethasone (IKd) versus daratumumab and carfilzomib and dexamethasone (DKd) in patients with relapsed or refractory multiple myeloma (RRMM).
Authors: AlRawashdh Neda , Choi Briana , Obeng-Kusi Mavis , Calamia Matthias , McBride Ali , Abraham Ivo 
Published: June 2021

e20010 Background: Isatuximab and daratumumab target the CD38 transmembrane glycoprotein on MM cells. IKd and DKd regimens have shown reductions of HR=0.53 (95%CI 0.32-0.89) and HR=0.63 (95%CI 0.46-0.85) resp. in progression or death risk compared to Kd in RRMM. In the absence of a direct IKd vs DKd trial, we performed an indirect treatment comparison on progression free survival (PFS) to enable cost-effectiveness analyses. Methods: A 3-state (pre-progression, progression, death) partitioned survival model was specified. NMA-adjusted transition probabilities were estimated from fitted exponential functions (time horizon of 6 and 12 m; cycle length 28 days). Inputs included the Wholesale Acquisition Cost of IKd, DKd, and premedications; cost of medication administration; and cost of adverse event management. Utility inputs for pre-progression (0.65) and progression (0.61) were per literature. Costs and utilities were discounted at 3.5%/y. A payer perspective was adopted. Life years (LY), quality adjusted LY (QALY), and incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR) were estimated in base case (BCA) and probabilistic sensitivity analyses (PSA). Cost-effectiveness acceptability curves (CEAC) were generated. Results: As detailed in the Table, 6m of IKd treatment was associated with incremental gains of 0.01 (PSA 0.01) LYs but no gains in QALYs at cost savings of $24,188 ($23,762), yielding a dominant ICER of $ -2,418,800 ($-2,376,200) per LYg (ICUR not estimable). Further, 12m of IKd treatment was associated with incremental gains of 0.04 (PSA 0.04) LYs (or 0.48m) and 0.02 (0.03) QALYs at incremental cost of $1,585 ($2,239), yielding ICER of $39,625 ($55,975) per LYg and ICUR of $79,250 ($74,633) per QALYg. Per CEAC, IKd is the dominated strategy in the 6m model and had probability of 50% of being cost-effective at WTP of $100,000 in the 12m model. Conclusions: Clinically, compared to DKd, IKd is associated with slight incremental gains in LYs of 0.12m over 6m and 0.48m over 1y. The 6m clinical gain comes with cost savings of approximately $24,000 or about 15% of IKd therapy, while the 12m gain requires a minimal cost commitment of around $2,000 or 0.6% of DKd treatment. These findings imply a clinico-economic benefit of isatuximab compared to daratumumab containing regimens in RRMM. [Table: see text]
Single cell multiomic analysis and immune cell type profiling of multiple myeloma with t(4;14).
Authors: deMel Sanjay , Scolnick Jonathan , Huo Xiaojing , Soekojo Cinnie , Song Fangfang , Ooi Melissa , Chng Wee Joo 
Published: June 2021

e20013 Background: Multiple Myeloma (MM) is an incurable plasma cell (PC) malignancy and high risk (HR) MM remains an unmet clinical need. Translocation 4;14 occurs in 15% of MM and is associated with an adverse prognosis. A deeper understanding of the biology and immune micro-environment of t(4;14) MM is necessary for the development of effective targeted therapies. Single Cell multi-omics provides a new tool for phenotypic characterization of MM. Here we used Proteona’s ESCAPE™ single cell multi-omics platform to study a cohort of patients with t(4;14) MM. Methods: Diagnostic bone marrow (BM) samples from 14 patients with t(4;14) MM were analysed using the ESCAPE platform from Proteona which simultaneously measures gene and cell surface protein expression in single cells. Cryopreserved BM samples were stained with 65 DNA barcoded antibodies and subsequently sorted on CD138 expression. The CD138 positive and negative fractions were recombined at a known ratio for analysis using the 10x Genomics 3’ RNAseq kit. Resulting data were analyzed with Seurat and MapCell. Results: The patients had a median age of 63 years. All received novel agent based induction. Median progression free and overall survival (PFS and OS) were 22 and 34 months respectively. MMSET was overexpressed in all PCs while FGFR3 expression could be categorized into zero cells expressing FGFR3, low expression (< 10% of cells expressing FGFR3) or high expression (> 80% of cells expressing FGFR3). We also found heterogeneity in the expression of cancer testis antigens (CTA) such as FA133A and CTAG2 between PC clusters across samples. Variation in the immune microenvironment of the BM was seen across all patient samples with no correlation between cell types and PFS or OS. However, an analysis of BM samples at diagnosis and relapse in one patient showed a shift in the ratio of T cells to CD14 monocytes with a ratio of 5.7 at diagnosis compared to 0.6 at relapse. Further analysis of PCs in this patient found 8 PC populations, each containing variable numbers of cells from both the diagnostic and relapse samples. This suggests that all populations present at relapse were also present at diagnosis, although at variable proportions. Increased expression of RCAN3 (associated with cereblon depletion) was detected at relapse. Conclusions: We present the first application of single cell multi-omics immune profiling in high risk MM. The heterogeneity in expression of CTA has implications for the application of immunotherapies, while the upregulation of RCAN3 may explain failure of immunomodulatory therapy. Our small sample size may explain the lack of correlation between gene or protein expression with clinical outcomes. We propose that t(4;14) MM is a genomically and immunologically heterogeneous disease. Single cell analysis of larger cohorts is required to build on our findings.
Patient-reported experience platform identifies discordance between guidelines and real-world practice: Maintenance therapy for high-risk multiple myeloma.
Authors: Sweeney Nathan W. , Goldsmith Scott Ryan , Crees Zachary , Molina Thomas H. , Ahlstrom Jenny 
Published: June 2021

e20022 Background: Patient-reported data play a critical role in assessing clinical benefit from therapeutic interventions and are increasingly used in clinical trials. Internet-based platforms such as HealthTree Cure Hub for Multiple Myeloma ( www.healthtree.org ) provide the opportunity to obtain such real-world patient-reported data, while also providing valuable insights into high-yield areas to focus on quality-improvement efforts. For example, proteasome inhibitor (PI)-based maintenance after autologous stem cell transplantation (ASCT) is a consensus recommendation in many practice guidelines for high-risk multiple myeloma (MM) yet real-world adherence to this practice remains uncertain (PMID 23541011, 30932732). Methods: We examined post-ASCT maintenance therapy in patients with high-risk MM, as defined per mSMART criteria, using patient-reported treatment data from the HealthTree Cure Hub for Multiple Myeloma database. Patients who received an ASCT prior to 2014 were excluded. Results: Our analysis identified 110 MM patients with high-risk MM. Of those, only 48 (44%) received PI-based maintenance therapy. Additionally, 60 (55%) received IMiD (immunomodulatory imide drug) maintenance, 1 (< 1%) received ‘other’, and 1 (< 1%) did not report maintenance therapy. Conclusions: The benefits of PI-based maintenance in MM are well established for high-risk MM. However, analysis of patient-reported data using an online patient portal, HealthTree Cure Hub for Multiple Myeloma, suggests a disparity between practice recommendations and real-world practice patterns. These findings, and others from online patient portals, can serve as a springboard in helping investigators to identify areas for quality-improvement initiatives.
Thyroid hormone receptor α1 acts as a new squamous cell lung cancer diagnostic marker and poor prognosis predictor: Can it be a novel therapeutic target?
Authors: Mohamed Fatma El Zahraa Ammar , Abdelaziz Ali Omar , Kasem Ahmed Hussein , Ellethy Tarek , Gayyed Mariana Fathy 
Published: June 2021

e20508 Background: Lung cancer is considered the first cause of cancer-related death worldwide. Unfortunately, all therapeutic regimens used in lung cancer treatment showed relatively equivalent efficacy. The search and subsequent testing of new therapeutic targets that can be used alternative to, after the failure of or in association with the currently used therapeutics to improve the prognosis is an urgent demand and consequently a very interesting era of oncological lung research. Up to date, it is known that Thyroid hormones and Thyroid hormone receptors (THRs) controls many tumors progression, nevertheless, its role in non-Small Cell Lung cancer (NSCLC) is not yet defineltly understood. This study investigated the expression of Thyroid hormone receptor alpha 1 (THRα1) in NSCLC cases. Methods: Immunohistochemistry using THRα1 antibody was performed on tissue sections collected from 80 patients diagnosed with NSCLC. We also analyzed the expression of THRα gene in Microarrays of squamous cell lung carcinoma (SCC) and adenocarcinoma (AC) patients by using GEO datasets on https://www.ncbi.nlm.nih.gov. Results: We showed, for the first time, the expression of THRa1 in NSCLC. Intermediate and high THRa1 expression was detected in (25% and 66.7%) of SCC cases respectively. High THRa1 expression was associated with shorter OS and poor prognosis. On the other hand, 86.7% of AC cases revealed low THRa1expression. By analyzing GEO data sets, a significant increase in THRa gene value was found in SCC compared to AC cases. Inflammatory cells in SCC cases showed high THRα1 expression. Conclusions: Our study is shedding a new light on the relevance of THRα1 in lung cancer not only as a possible prognostic marker but also as an innovative diagnostic additive tool for lung squamous cell carcinoma which could be tested as a therapeutic target as well.