bluuebunny/crossref_metadata_2025_split huggingface dataset:
Weekly paclitaxel (P), carboplatin (CP) plus pembrolizumab (PMB) as first-line treatment of recurrent or metastatic (R/M) or locally very advanced (LVA) head and neck squamous cell carcinoma (HNSCC): A retrospective study in 39 patients (pts).
Authors: Borel Christian , Carinato Hélène , Pflumio Carole , Poprawa Elodie , Brahimi Youssef , Oriel Marine , Vacheret Clara , Ravily Delphine , Coliat Pierre , Petit Thierry , Burgy Mickael 
Published: June 2024

e18018 Background: Since the results of the KN-048 trial, the combination of platinum/5FU plus PMB has become the standard of care (SOC) for R/M HNSCC pts. The KN-B10 study shows that 5FU can be replaced by P with a favorable response rate and toxicity profile. Weekly use of P reduces hematologic toxicity and increases dose-intensity. Methods: We retrospectively reviewed all records of patients with R/M or LVA (T4b and/or N3b) HNSCC, ECOG-PS 0 to 2, PDL1 CPS ≥ 1, treated in first-line with weekly P (80 mg/m2) and CP (AUC 2: maximum total dose of 250 mg and systematic G-CSF at D3 and D4) for up to 12 infusions plus PMB every 3 weeks for up to 35 administrations. Results: From July 2020 to April 2023, 39 pts (median age 63 years, 74% male, 18% PS2) were treated. Primary tumors: oropharynx 44%, larynx 23%, hypopharynx 18% and oral cavity 15%. Disease setting: LVA 20%, local recurrence in irradiated area 54%, local recurrence and distant metastases 10% distant metastases only15%. With a median follow-up of 19 months (m), median Overall Survival (mOS) was 17.2 m (95%CI: 10.8-NR). 31/39 (79%) pts achieved an objective response (OR): 7 CR and 24 PR. For the 8 LVA pts, all achieved an OR, with a median Event Free Survival of 10 m (95%CI: 6.27-NR): the 4 progression-free pts (8.6 m+ to 25 m+) were treated with radiotherapy after neoadjuvant immuno-chemotherapy. For the 31 R/M pts, ECOG-PS was a significant prognostic factor of OS, mOS: 19.3 m (95%CI: 14.4-NR) for ECOG-PS 0-1 pts vs. 10.3 m (95%CI: 5.4-13.9) for ECOG-PS 2 pts (p = 0.02). For R/M pts, median Progression Free survival was 6.9 m (95%CI: 4.4-8.6) and the ORR was 74%, with a median duration of response of 6.5 m (95%CI: 3.13-8.56). Toxicity was manageable, with 20 (51%) pts experiencing at least one grade 3-4 adverse event: hematologic 18% (including one febrile neutropenia), infection 5%, neuropathy 8%, diarrhea 8%, infusion reaction 8%, electrolyte disturbances 8%, renal failure 3% and no toxic deaths. Conclusions: The combination of weekly P and CP plus PMB produces a high ORR and increased OS consistent with the results of the Frail-Immune study (J. Fayette ASCO 2023). This regimen deserves further consideration not only in the R/M setting, but also in the neoadjuvant setting for locally advanced patients.
Precision medicine for papillary thyroid carcinoma (PTC) variants: A machine learning approach to prognosis and treatment guidance.
Authors: Alshwayyat Sakhr Abdulsalam , Alenezy Abdalwahab , Asha Wafa , Alshwayyat Mustafa , Kamal Haya , Ghammaz Owais , Alshwayyat Tala Abdulsalam 
Published: June 2024

e18072 Background: PTC is a common endocrine cancer with a good prognosis, but aggressive subtypes, such as Hürthle cell (HCC) and columnar cell variants (CCV), pose challenges due to their higher recurrence and metastasis rates. To provide personalized care, we applied machine learning to evaluate the treatment effectiveness and develop precise prognostic models for PTC variants. Methods: The Surveillance, Epidemiology, and End Results (SEER) database provided the data used for this study’s analysis (2000–2019). Patients who met any of the following criteria were excluded: diagnosis not confirmed by histology, previous history of cancer or with other concurrent malignancies, and unknown data. To identify prognostic variables, we conducted Cox regression analysis and constructed prognostic models using machine learning (ML) algorithms to predict the 5-year survival. Patient records were randomly divided into training (70 %) and validation (30 %) sets. A validation method incorporating the area under the curve (AUC) of the receiver operating characteristic curve was used to validate the accuracy and reliability of the ML models. Results: The study population comprised 3690 patients. Among them 3180 patients with CCV and 510 patients with HCC, respectively. Most patients (62.8%) were 45 years or older, with a median age of 52 years. A total of 56.9% of patients had a tumor size greater than 2 cm, with a median tumor size of 3.1 cm. The largest racial group was white, comprising 83.8% of the cases, and 11.8% of the cases were Asian. Most cases were regional (53.4%, n=1969), followed by localized (38.3%, n= 1413). Multivariate Cox regression analysis revealed that N1 negatively affected the survival of HCC patients. CCV has a favorable prognosis after surgery, radiotherapy, or total thyroidectomy. Poor prognosis in CCV is associated with black race, large tumor size, and T4 stage. Improved survival in the localized/regional stage and decreased survival with male sex, older age, distant metastasis, and advanced AJCC stage in both PTC subtypes. ML models revealed that the random forest classifier (RFC) and K-Nearest Neighbors (KNN) accurately predicted outcomes, followed by Logistic Regression (LR) models. The highest contributing factors were AJCC staging, tumor size, and T aspect of TNM staging. Conclusions: Our study offers a method for evaluating and treating patients with PTC variants. The machine learning model that we created serves as a useful and personalized resource to aid in clinical decision-making processes.[Table: see text]
Cytogenetic and molecular features of mixed-phenotype acute leukemia in US veterans and its potential impact on therapy.
Authors: McKinnell Zoe , Degann Seta , Karel Daniel , Antonio Martha , Nassereddine Samah , Neppalli Amarendra Kumar , Jain Maneesh Rajiv 
Published: June 2024

e18535 Background: Mixed phenotype acute leukemia (MPAL) is a rare and heterogeneous subtype of acute leukemia. Per the 2022 WHO criteria, it is categorized based on its predominant immunophenotypic lineage (B vs. T) and the presence of a Philadelphia chromosome (Ph+) or a KMT2A rearrangement. While many other cytogenetic and molecular abnormalities have been described, due to the rarity of this disease, neither their incidence nor the role of targeted therapies has been well defined. We conducted a retrospective study of all veterans with MPAL diagnosed between 2000-2023 to examine the impact of different clinical, immunophenotypic, cytogenetic, molecular, and treatment strategies on overall survival (OS). Methods: Electronic medical record data from the Veterans Affairs Informatics and Computing Infrastructure database were used to identify 320 patients diagnosed with MPAL between 2000-2023 using the text utilization integration feature to query all notes. All patient charts were reviewed manually. Pathology reports and clinical notes were reviewed to collect data on diagnosis, treatment, and outcome. To date, 74 patients have been identified and included in this preliminary analysis. Cox regression analyses were used to compare OS between patients with different MPAL subtypes, cytogenetic, and molecular features as well as different treatment approaches. Multivariate analysis was performed with controls for age, race, and BMI. Results: In line with prior research, decreases in OS were seen among older patients > 65 yo compared to patients <30 yo and those who received an AML induction over ALL induction regimen with HR of 8.28 (p 0.04) and 2.02 (p 0.03) respectively. Patients who had a transplant had significantly improved OS with a HR of 0.19 (p <0.001). Of the 32 patients who had potentially targetable mutations, 14 received targeted maintenance therapy with either Ph+ or FLT3 inhibitors. Patients who got targeted maintenance therapy (including FLT3 inhibitors) had an OS of 55 months compared to 17 months for those who did not. 50% of those patients who did not get maintenance therapy went to transplant and 31% of patients who did get maintenance therapy went to transplant yet these patients still had improved OS. Conclusions: This preliminary data demonstrate that while MPAL is a complex and heterogeneous disease, a significant portion of patients have targetable mutations. Further studies evaluating targeted therapies such as FLT3, IDH, and menin inhibitors in MPAL patients may be warranted. [Table: see text]
CD19 expression in diffuse large B-cell lymphoma (DLBCL) patient biopsies after treatment with tafasitamab.
Authors: Volgina Alla , Rumberger Beth , Johannsdottir Hrefna , Larsen Thomas Stauffer , Alvarez Arias Diana 
Published: June 2024

e19050 Background: Tafasitamab (tafa) is a CD19-targeting immunotherapy that induces enhanced antibody dependent cellular cytotoxicity and phagocytosis. Tafa received accelerated FDA approval in 2020 for treating relapsed or refractory DLBCL in combination with lenalidomide in patients ineligible for autologous stem cell transplant, based on results from L-MIND, a multicenter, open-label, single-arm, phase 2 trial. FirmMIND (NCT05429268) is an ongoing identical study, further evaluating efficacy and safety of tafa in this setting. Several other CD19 targeting agents are available; however, CD19 antigen loss following treatment with chimeric antigen receptor T-cell therapy targeting CD19 (CART19) has raised concerns over CD19-targeted therapy sequencing. Loss of CD19 has not been observed to date in tafa clinical trials or practice. Methods: To evaluate CD19 expression at screening and after disease progression in firmMIND, we developed an immunohistochemistry (IHC) assay using a mAb that binds to an intracellular epitope of CD19 clone LE-CD19. To validate that CD19 expression is detectable after tafa treatment, we treated cultured SU-DHL-4 or Jurkat cells with tafa at a saturating concentration for 24 hours. After washing out unbound tafa, cells were harvested at specific timepoints. Resulting cell line blocks were assessed for CD19 expression by IHC. We also monitored CD19 trafficking in response to fluorescently labeled tafa by confocal microscopy. Results: By IHC, CD19 expression was comparable between treatment conditions, suggesting the assay can effectively measure CD19 expression in lymphoma biopsy samples post-tafa. Confocal microscopy showed a fraction of tafa-bound CD19 internalized and colocalized with a CD19 intracellular pool labeled with anti-CD19 mAb clone EPR5906; this mAb also detected CD19 that remained localized on the cell surface. The data demonstrated that CD19 persists on tumor cells after tafa treatment at levels that could be bound by other CD19-targeting therapies. As of the January 25, 2024 data cutoff, we received 6 end-of-treatment (EOT) samples from patients in firmMIND. Biopsies were collected 14-26 days after the last tafa dose; 5 of 6 samples were biopsies from lymph nodes or liver and showed ≥80% of tumor cells staining CD19+ on membranes with 3+ intensity by IHC, except 1 that was collected only 6 days after last dose and showed 50% positivity. The sixth biopsy (extranodal subcutaneous lesion) showed no CD19 expression at baseline or EOT. Conclusions: Patient biopsy analysis and preclinical data suggest that following tafa treatment, CD19 antigen is preserved on the surface of tumor cells after short and transient internalization and could be targeted by other CD19 agents, such as CART therapy. This conclusion is supported by sequential treatment with tafa followed by CART in vivo (Sakemura, 2024). Analyses are ongoing to confirm these findings.
Health-related quality of life (HRQoL), functioning, and symptoms with odronextamab monotherapy in patients (pts) with relapsed or refractory follicular lymphoma (R/R FL) by POD24 status in the ELM-2 study.
Authors: Villasboas Jose Caetano , Mayer Laura Magnano , Tessoulin Benoît , Cho Seok-Goo , Taszner Michal , Novelli Silvana , Luminari Stefano , Merli Michele , Ubieto Ana Jiménez , Poon Michelle , Tucker David , Walewski Jan Andrzej , Ivanescu Cristina , Chaudhry Aafia , Mohamed Hesham , Ambati Srikanth R. , Harnett James , Kamat Siddhesh , Kim Tae Min ,   ELM-2 Investigators
Published: June 2024

e19057 Background: In ELM-2 (NCT03888105), a Ph 2, single arm, open label trial, odronextamab demonstrated robust efficacy, generally manageable safety, and overall maintenance of patient-reported outcomes (PROs) in R/R FL pts (Villasboas et al. ASH 2023). In FL, pts with disease progression within 2 yrs of frontline chemoimmunotherapy (POD24) are hard to treat with poor clinical outcomes, representing an unmet need. We report PROs by POD24 status in pts with Grade 1–3a R/R FL from ELM-2. Methods: Pts received IV odronextamab in 21-day cycles (C): 80 mg QW in C1–4, with C1 dose step up to mitigate cytokine release syndrome, then 160 mg Q2W (Q4W if complete response ≥9 mo) until progression. PROs were collected at baseline (BL), Wks 2–4, 10, then Q8W in Yr 1, and Q12W in Yr 2. Post-hoc POD24 subgroup analyses were performed on six EORTC QLQ-C30 scales, the EQ-5D-3L VAS, and FACT-Lym LymS. Estimated mean change from BL (CFB) was analyzed using mixed models for repeated measures (MMRM) through Wk 42 (≥10 pts at last assessment). Published meaningful CFB thresholds were used to define deterioration/improvement in responder analyses. Results: By Jan 31, 2023, 140 pts with R/R FL had received odronextamab. Pts with POD24 (n=70) were younger than pts without POD24 (n=70; median age 57.5 vs 62.0 y), had fewer prior Tx lines (median 2 vs 3), and a higher proportion double refractory to anti-CD20 Ab + alkylator (53% vs 29%). Objective response rate was similar in evaluable pts with (n=63; 79%) and without (n=65; 80%) POD24. PRO questionnaire completion ranged from 52–95% through Wk 42 across groups. Descriptive analyses suggest BL PRO scores were similar by POD24 status, showing good HRQoL/functioning and low symptom burden, and were generally maintained through Wk 42 with minimal between-group differences (overlapping 95% CIs for LS mean CFB [Table]). In both groups, more pts reported PRO maintenance or improvement vs deterioration across visits, except for fatigue at Wk 10 in pts without POD24. Conclusions: In pts with heavily pretreated R/R FL, odronextamab Tx maintained HRQoL, functioning, and symptoms irrespective of POD24 status. Clinical trial information: NCT03888105 . [Table: see text]
Gender disparities in Waldenstrom macroglobulinemia: Insights from a comprehensive analysis.
Authors: Kaldas David , Thapa Shrinjaya , Shariff Bushra , Modukuri Shrikar , Shain Kenneth H. , Blue Brandon Jamaal , Chavez Julio C. , Baz Rachid C. , Grajales-Cruz Ariel Felipe 
Published: June 2024

e19064 Background: Waldenstrom Macroglobulinemia (WM) is a rare, complex hematological malignancy with paucity of research about the landscape of gender disparities regarding clinical phenotype, genotype and outcomes. The aim of our abstract to identify those gender-based variations in WM. Methods: This is a retrospective study using a large WM database at Moffitt Cancer Center (MCC). We reviewed the baseline characteristics and molecular information of patients evaluated at MCC from years 1995 to 2020 and outcomes based on gender. Chi-square tests were used for comparing categorical variables and t-test for continuous variables. Kaplan-Meier method was used to compare survival. Results: Total of 265 patients with WM were identified, 63% (167) were males and 37% (98) were females. Mean age at diagnosis was 76 years for both groups, most of the patients were white non-Hispanics (94% in men vs 96% in women) (P=0.09) and had performance status (PS) 0 at diagnosis, 63% in men, 70% in women. The table summarizes baseline characteristics based on gender, men had slightly lower hemoglobin mean 11.1 vs11.5 in women (P =0.013), lower platelet count mean 209 vs 264 in women (P=<0.001) and slightly lower albumin mean 3.8 vs 3.92 in women (P=0.0445). Hyperviscosity and plasmapheresis were more in women 10% vs 2% in men (P=<0.001), Cryoglobulinemia was more in men 11% vs 1% (P=<0.001). There were no statically significant gender differences based on the presence of mutations in MYD88, CXCR4, tp53, or del6q. The median overall survival (mOS) was slightly longer in lower-risk WM female pts, but not in high-risk (based on International Prognostic Scoring System for WM). The overall mOS was 98 months (mo) for females compared to 95 for males, P=0.004. The mOS for low-risk WM was 137 vs 132 mo, for intermediate risk 89 vs 87 mo, and for high-risk 37 vs 39 mo respectively for females and males (P=<0.001). The rate of Diffuse Large B Cell Lymphoma transformation was not different (7% and 4%, respectively for women and men, (P=0.11) Women were more likely to respond to Bendamustine + Rituximab (BR)/BR + steroids than men (43%vs 25%, p=0.04)There were no differences in response to Cytoxan+ Rituximab+ Prednisone, Bruton’s tyrosine kinase inhibitors, or Venetoclax treatment. Conclusions: This retrospective review of a large database of WM patients highlights important gender differences in clinical WM disease features. Women had better overall survival, mainly in lower risk WM and higher responses to immunosuppressive therapy. Although disparities in WM may be multifactorial, disparities based on gender needs more studies to be explored for better understanding of the disease biology and outcomes. [Table: see text]
Effect of 1-L-MT on immunotherapy of diffuse large B-cell lymphoma via downregulation of PD-L1.
Authors: Chengtao Sun , Xu Xue , Yao Chunping 
Published: June 2024

e19066 Background: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma, accounting for more than 30% of all cases. Although with the development of treatment, the 5 years overall survival rates remain low, range from 30%-50% for all DLBCL patients. In addition to R-CHOP, immunotherapy has attracted much attention. However, the single-agent activity of most immune checkpoint inhibitors (ICI) in DLBCL has been overwhelmingly disappointing. It is urgent to develop new methods to enhance the efficacy of DLBCL treatment. Our previous study demonstrated that 1-L-MT, an IDO1 inhibitor, can inhibit tumor growth of DLBCL. Here, we investigate whether 1-L-MT promotes antitumor immunity of ICI in DLBCL. Methods: The role of 1-L-MT on cell proliferation in vitro and tumor growth in NOD/SCID mice were investigated. RNA-seq analysis was performed in 1-L-MT treated and control OCI-Ly10 cells. ChIP assay was performed using AhR-precipitated DNA samples of OCI-Ly10 cells (treated with or without 1-L-MT) and primers for PD-L1, and he expression of PD-L1 was evaluated by RT-qPCR. The combination of 1-L-MT and PD-1 blockade therapy were performed in C57BL/6 mouse bearing tumor cells to evaluate the antitumor activity. Results: In our study, IDO1 inhibitor 1-L-MT sensitized diffuse large B cell lymphoma to immunotherapy via downregulation of PD-L1. Further study confirmed that 1-L-MT could reduce the expression of PD-L1 and upregulate the expression of MHC-I antigen presentation factors. In addition, RNA-seq and bioinformatics analysis revealed that the transcription factor AhR may involved in the downregulation of PD-L1 transcription level induced by 1-L-MT. Mechanistically, ChIP and RT-qPCR assays were conducted to test AhR-PD-L1 interaction, and the results showed that AhR directly bound the promoter of PD-L1. 1-L-MT-mediated PD-L1 reduction promoted T cell activation and T cell killing of tumor cells. The combination of 1-L-MT and anti PD-1 antibody significantly inhibited DLBCL growth and extends the lifespan of tumor-bearing mice. Conclusions: Our study unveiled a mechanism by which 1-L-MT induces PD-L1 downregulation via AhR and provides methods to facilitate immunotherapy in diffuse large B-cell lymphoma. The present study may provide a theoretical foundation for overcoming the challenge of low-sensitivity to immunotherapy in DLBCL.
External validation of the lactate dehydrogenase/albumin ratio as a clinical predictor of overall survival in Peruvians with diffuse large B cell lymphoma.
Authors: Pichardo-Rodriguez Rafael , Beltran Garate Brady E , Castro-Uriol Denisse , Paredes-Noguni Sally , Vela-Ruiz Manuel , Alarcon Rozas Ashley Efrain , De La Cruz-Vargas Jhony A. , Vilela Luis 
Published: June 2024

e19072 Background: The lactate dehydrogenase/albumin ratio (RLA), a potentially promising inflammatory biomarker derived from the division of serum lactate dehydrogenase and albumin values, has shown a strong correlation with overall survival (OS) in patients with diffuse large B-cell lymphoma (DLBCL). However, its validity in our specific population requires confirmation. We aimed to validate the RLA as an early predictor of OS in a cohort of Peruvian patients with DLBCL. Methods: We conducted a retrospective cohort study recruiting consecutive patients diagnosed between 2009 and 2017, with the last follow-up on July 1, 2022, at the National Hospital Edgardo Rebagliati Martins and the Maria Auxiliadora Hospital. The optimal cutoff point for RLA was estimated using ROC curve analysis, and survival curves were plotted and analyzed using Cox regression and Kaplan-Meier methods with the Log-Rank test. Results: A total of 283 patients with a median follow-up of 2.6 (range: 0.02-10.51) years were included. The optimal cutoff point for RLA was established at 23.6. Values below 23.6 were associated with poor OS when comparing survival curves (p<0.001). In the multivariate model, a prognostic association was found between RLA and OS (HR: 3.37, 95% CI: 1.78-6.39, p<0.001). Conclusions: The RLA is confirmed as a valid biomarker in our population for predicting OS in patients with diffuse large B-cell lymphoma (DLBCL), allowing for early evaluation. [Table: see text]
Characteristics and outcomes of plasmablastic lymphoma in a predominantly Hispanic population.
Authors: Kolawa Adam Alexander , McLain Julian Hardy , Ye Shirley , Siddiqi Imran , Mohrbacher Ann 
Published: June 2024

e19079 Background: Plasmablastic lymphoma (PBL) is a rare subtype of diffuse large B-cell lymphoma and is frequently associated with immunosuppression. PBL displays immunoblastic morphology and a plasma cell immunophenotype. Data regarding patient characteristics, outcomes, and optimal treatment for this disease is limited. The reported prognosis of patients with PBL has been historically poor, with median overall survival ranging from 6 to 18 months. A recent publication of the SEER/NCDB database found a significantly improved OS in the Hispanic population (HR 0.7, p=0.014). This study investigates demographic, treatment, and survival outcomes for a primarily Hispanic PBL population. Methods: We identified 42 cases of pathologically confirmed PBL at two high volume tertiary care centers in Southern California between March 2010 and June 2023. Chart review was used to collect data on clinical presentation, treatment, and outcomes. Results: Median age of patients at diagnosis was 46 years (range 17-91 years) and 90% were male. Hispanic patients represented 81% of the total cohort. Predisposing immunosuppression was identified in 60%, and 50% of the total cohort were HIV-positive. Pathologic analysis showed EBV positivity by EBER in situ hybridization in 67%. 76% of patients presented with advanced disease (Stage III/IV). The most common regimens were EPOCH (27%) and V-EPOCH (49%). Response rates and CR rates were 63% and 50% respectively. Median follow-up was 10.5 months. OS was 72% at 1-year and 60% at 2-years. Conclusions: Our cohort demonstrated a 1-year OS of 72% compared to the 56% 1-year OS for PBLs in the SEER/NCDB database. There was no statistically significant difference in survival between the Hispanic and Non-Hispanic cohorts in our study. However, this is likely due to the small sample size in the latter. Notably, our patient population had more advanced disease at presentation (76% Stage III/IV) than the SEER/NCDB cohort (60% Stage III/IV). This improved survival is likely multifactorial, but could represent ethnic differences in PBL biology, high EBV positivity, and the frequent utilization of higher intensity regimens (EPOCH/V-EPOCH = 76%). Further studies are needed to better characterize this disease in the Hispanic population. [Table: see text]