tbuckley/cabot-search huggingface dataset:
Characteristics, treatment, and outcomes of cutaneous mantle cell lymphoma: A decade-long study at MD Anderson Cancer Center.
Authors: Charles Gaulin, Jared R. Zhang, Susan Y. Wu, Preetesh Jain, Chi Ok, Fangfang Yan, Wendy Chen, Onyeka Oriabure, Bouthaina Shbib Dabaja, Jillian Rebecca Gunther, Penny Fang, Chelsea Camille Pinnix, Michael Wang
Journal: Journal of Clinical Oncology (2024)

e19037 Background: Mantle cell lymphoma (MCL) is a rare B cell neoplasm that accounts for 6% of all non-Hodgkin lymphomas and affects predominantly older Caucasian males. Cutaneous involvement is rare in MCL, but more commonly occurs in the advanced or terminal stages of the disease and lacks a standardized approach. Here we report our center’s experience with cutaneous MCL. Methods: We conducted a retrospective chart review of all MCL patients treated at the University of Texas MD Anderson Cancer Center from January 2013 to December 2023 and identified 20 MCL patients with cutaneous involvement. Demographic data, disease characteristics, imaging findings, therapies, and survival outcomes were collected. The study was performed in accordance with the guidelines of the institutional review board. Results: Among the 20 MCL patients with cutaneous involvement (Table), nearly all were Caucasian (n=19/20, 95%), and most were male (n=14/20, 70%). The median age at cutaneous MCL diagnosis was 63.5 years (range: 50-83). All patients had advanced stage disease. The median interval from MCL diagnosis to the emergence of cutaneous symptoms was 2.2 years (range 0-9.3). Most had relapsed/refractory disease (n=17/20, 85%). Most patients had blastoid (n=13/19) or pleomorphic (n=4/19) cytology with a Ki-67 proliferative index ≥50% (n=19/20, median 90%). Several patients had p53 expression (n=11/14) and/or TP53 aberrations (n=4/16). Immediate subsequent systemic therapy, most commonly immunochemotherapy (n=9/20), led to frequent responses (overall response rate: 61%). Most patients received low-dose radiotherapy (RT) for their cutaneous disease (n=19/20) achieving high rates of local control (n=16/18). Of those who are alive and in complete response (n=3) at data cutoff, 2 received chimeric antigen receptor (CAR) T cell therapy as their last MCL-directed treatment. The median survival time from MCL diagnosis to death was 6.83 years (95% confidence interval (CI):4.20-not estimable (NE)). The median survival time from the diagnosis of cutaneous involvement to death was 3.16 years (95%CI: 1.93-NE). The median follow-up duration from MCL diagnosis was 8.22 years. Conclusions: Cutaneous involvement in MCL is associated with aggressive disease biology and poor survival outcomes. Low-dose RT with concurrent immunochemotherapy should be considered the current standard therapeutic approach. CAR T cell therapy and/or bispecific T cell engagers may further improve outcomes in these high-risk patients. [Table: see text]
Intratumoral and fecal microbiota to reveal microbial markers associated with gastric carcinogenesis.
Authors: Yiwen Wang, Wenjie Han, Yue Wang, Tao Sun, Junnan Xu, Li Han, Xiaolin Liu
Journal: Journal of Clinical Oncology (2024)

e16014 Background: The relationship between dysbiosis of the gastrointestinal microbiota and gastric cancer (GC) has been extensively studied. However, microbiota alterations in GC patients vary widely across studies, and there are still no diagnostic biomarkers for early GC that can be replicated in multiple populations. Therefore, this study aimed to characterize the gastrointestinal microbial communities associated with gastric carcinogenesis. The diversity results showed significant differences in GC patients' intratumoral microbiota compared with the non-GC population. Methods: 1,642 gastric tissue samples and 394 fecal samples were tested using 16s rRNA amplicon sequencing. After identifying taxa with differential biomarkers, we built a random forest model to distinguish gastric cancer from normal controls. We validated the generalizability and specificity of the model using an external cohort. In addition, we used the KEGG database for predictive analysis of colony correlation functions. Results: The positive correlation between GC-enriched bacteria increased, and the positive correlation between GC-depleted bacteria decreased compared to healthy individuals. Functional analysis revealed that carbohydrate and iron metabolism pathways significantly enriched in the GC phase. In addition, we explored non- Helicobacter pylori ( HP) commensals, which play an essential role in HP-negative and HP-positive GC. Finally, random forest models were constructed using the specific taxa associated with GC obtained from the Lefse analysis, and it was found that the combination of Lactobacillus and Streptococcus included alone could well discriminate between GC patients and healthy individuals in fecal samples (area under the curve (AUC) = 0.7949). We also validated it in an independent cohort (AUC = 0.7712). Conclusions: This study demonstrates the validity of GC-specific microbial markers across multiple populations, which may contribute to early non-invasive diagnosis of GC.
Efficacy and safety of immunotherapy in patients with liver metastases in patients with esophageal cancer: A retrospective, real-world study.
Authors: Tiejun Ren, Dingyi Wang, Jinjin Gu, Lijuan Zhao
Journal: Journal of Clinical Oncology (2024)

e16033 Background: Advanced or metastatic esophageal cancer patients tend to have a poor prognosis. The liver is the most common organ of distant metastasis in esophageal cancer. The liver metastases associated with a higher risk of survival. Developing the optimal treatment modalities is especially important for those patients. The efficacy of programmed cell death protein 1 (PD-1) or its ligand (PD-L1) inhibitors have not been clearly clarified in liver metastasis of esophageal cancer. Methods: This is a single-center, retrospective, real-world study. We collected general information and clinical data from patients with liver metastasis of esophageal cancer who admitted to Luoyang Central Hospital between April 2020 and October 2023. All patients were first diagnosed esophageal cancer with liver metastasis and received PD-1 or PD-L1 inhibitor regimen or chemotherapy regimen for the first time. Patients treated with interventional therapy or who had received PD-1 or PD-L1 inhibitors were excluded. The efficacy and safety of patients receiving immunotherapy were evaluated, including overall survival (OS), objective response rate (ORR), progression-free survival (PFS), disease control rate (DCR), grade 3-5 treatment-related adverse events (TRAE), and immune-related adverse events (irAE). We also evaluated the relationship between clinical features and outcomes using univariate and multivariate analyses. Results: We enrolled 61 patients with a median age of 61 (44-88) years, 63.9% males; 37 in the immunotherapy group (23 in the first-line group, 62.2%) and 24 in the chemotherapy group (19 in the first-line group, 79.2%). Median OS was 14.1 (95% CI 11.4-16.8) months in the immunotherapy group and 9.2 (95% CI 8.5-9.9, p &lt; 0.01) months in the chemotherapy group; In first-line treatment, the median OS in the two groups was 19.4 (95%CI 15.0-22.2) months and 9.6 (95%CI 8.9-10.3, p &lt; 0.01) months. In all patients, Median PFS was 7.2 (95% CI 6.4 – 8.0) months in the immunotherapy group and 4.6 (95% CI 3.8 – 5.4) months in the chemotherapy group, p = 0.174. The ORR of immunotherapy and chemotherapy was 56.8% and 33.3%; DCR was 78.4% and 62.5%. Univariate and multivariate analysis showed that N stage and treatment regimen were significant factors related with OS. Grade 3 TRAE in immunotherapy group and chemotherapy group were 29.7% and 29.2%, respectively. The incidence of irAEs was 10.8%. No treatment-related deaths occurred. Conclusions: This real-world data showed PD-1 or PD-L1 inhibitors might have good efficacy and manageable safety in EC patients with liver metastases, especially in first-line patients. [Table: see text]
The role of determining HER2neu status in patients with gastric cancer.
Authors: Rabiga Kadyrbayeva, Dilyara Kaidarova, Kaldigul Smagulova, Elmira Medetbekova, Innara Turkpenova, Maria Dmitrenko, Samat Kaldarbekov, Ayaulym Nurmukhambet
Journal: Journal of Clinical Oncology (2024)

e16067 Background: Over the past two decades, gastric cancer has continued to maintain a leading position in both incidence and mortality rates among all malignant neoplasms in the Republic of Kazakhstan. Recent data indicate that amplification or overexpression of the HER2 gene is detected in 7-34% of gastric cancer cases, significantly impacting treatment outcomes. Studying a specific group of patients with HER2 overexpression in gastric cancer is of great interest in clinical oncology. Research aim: To examine the long-term treatment outcomes in patients with gastric cancer depending on the status and level of HER-2 expression in real clinical practice. Methods: Analysis was conducted on 172 formalin-fixed paraffin-embedded samples of gastric adenocarcinoma and gastroesophageal junction carcinoma, subjected to immunohistochemical examination to determine HER2 protein expression. Patients' ages ranged from 18 to 85 years, with a mean age of 61.7 years; among them, 106 (61.6%) were male and 66 (38.4%) were female. Of the 172 patients, 64 (37.2%) had primary tumors located at the gastroesophageal junction, while 108 (62.8%) had tumors located in the body of the stomach. Based on differentiation grade, the majority were G3-100 (50%), G2-91 (45%), G1-9 (5%). HER2 testing was performed on the Ventana BenchMark Ultra platform using the HER2 (4B5) antibody. Results: HER2 overexpression was detected in 26 (15.1%) of the 172 patients. Patients with HER2 2+ non-amplified were 6 (3.5%), HER2 2+ amplified were 8 (4.6%), HER2 1+ was detected in 19 (11%) cases, and HER2 0 was found in 121 (80.9%) cases. Long-term results revealed statistically significant differences, notably the highest overall survival rate in patients with HER-2 overexpression compared to HER-2 low and absence of HER-2. The HER2 3 (+FISH/SISH) variant was significantly more prevalent in 84.6% compared to HER2 0 in 52%, and HER2 1 in 48%, p &lt; 0.05. Comparison of Her2 status using the chi-square method in groups revealed probable differences concerning tumor localization, with a criterion value of 0.034; morphological form (criterion value = 5.83); and differentiation grade (criterion value = 10.05). Conclusions: These results underscore the importance of further HER2 research in gastric cancer and gastroesophageal junction carcinoma for the development of personalized therapeutic strategies.
Long term results of a new treatment strategy for follicular low grade lymphoma (FLGL).
Authors: Fernando Cabanillas, Thyra Gutierrez Sierra, Adelba Torres, Jose Abreu-Albelo, Fredrick B. Hagemeister
Journal: Journal of Clinical Oncology (2024)

e19035 Background: FLGL usually presents with widespread but asymptomatic lymphadenopathy, low SUVs on PET and normal LDH. It's considered incurable and standard of care has been 'watch and wait' (W&amp;W) followed later by treatment if necessary. We have described a subset of patients that we termed clinically discordant indolent histology (“CDIH”) whose behavior is more aggressive. CDIH is defined as presence of any of these: B symptoms, high LDH, SUV &gt;14 on PET, Ki-67 index &gt;30% or involvement of areas such as lung, pleura, soft-tissue, CNS and bones. Our study aims to assess real-world long-term outcome of managing FLGL with and without CDIH. Methods: We analyzed 186 previously untreated FLGL cases treated at our center from June 2002-July 2023, without opting for W&amp;W. CDIH cases typically received R-CHOP x6, then 4 FND. Non-CDIH mainly received FND-R. All received 2 years maintenance rituximab. Main objective was to assess 10-year PFS and OS of stage IV cases, comparing it in a real-world setting against our previously published MD Anderson (MDACC) data. Secondary objectives were to compare our 10-year PFS and OS in stage IV cases against historical controls based on the FLIPI-2 score. We also sought to determine prognostic value of CDIH as compared to FLIPI-2, evaluate early relapse rate (2 yrs), and assess rate of transformation to aggressive lymphoma. Results: Median age: 58 (26-93). Median follow up: 96 mos (6-261). Stage III-IV: 76%. CDIH was present in 56%. Our PFS 10 yrs for non-CDIH=96% vs CDIH=77% (p=0.002). For stage IV, PFS 10 yrs = 82% vs MDACC's 50% using FND-R. OS 10-yr= 90% vs MDACC's 85%. 67 pts were followed &gt;10 years; a relapse occurred in only 5 (7%). Our PFS 10 yr for favorable FLIPI-2 (score 0)= 97%, for intermediate (1-2) =88%, unfavorable (3-5)= 72% (p=.15). Our PFS results were consistently superior to literature data across all FLIPI-2 scores. Transformation to DLBCL= 6/186 (3%) compared to 20-30% historical controls; 5 of 6 transformations were in cases with CDIH and 4 occurred within 3 yrs. Early (&lt;2 yr) relapse rate= 2% in contrast with 20% literature data; all 4 early relapses were CDIH. Conclusions: Our findings emphasize several advantages of initiating treatment early and basing it on presence or absence of CDIH. Our data highlight the need to 1- identify CDIH for potential use of doxorubicin treatment. 2- CDIH as prognostic factor seems more effective than FLIPI-2. 3- PFS 10 yr results are remarkably superior to both literature controls and to our previous experience at MDACC with FND-R. 4- Only 7% relapses beyond 10 yrs suggest potential for cure, according to our results and those from MDACC. [Table: see text]
Natural killer cell-derived exosome-based cancer therapy: from biological roles to clinical significance and implications
Authors: Chaohua Si, Jianen Gao, Xu Ma
Journal: Molecular Cancer (2024)

Abstract Natural killer (NK) cells are important immune cells in the organism and are the third major type of lymphocytes besides T cells and B cells, which play an important function in cancer therapy. In addition to retaining the tumor cell killing function of natural killer cells, natural killer cell-derived exosomes cells also have the characteristics of high safety, wide source, easy to preserve and transport. At the same time, natural killer cell-derived exosomes are easy to modify, and the engineered exosomes can be used in combination with a variety of current cancer therapies, which not only enhances the therapeutic efficacy, but also significantly reduces the side effects. Therefore, this review summarizes the source, isolation and modification strategies of natural killer cell-derived exosomes and the combined application of natural killer cell-derived engineered exosomes with other antitumor therapies, which is expected to accelerate the clinical translation process of natural killer cell-derived engineered exosomes in cancer therapy.
Dose optimization and exposure-response analyses to support optimal dose of ABBV-400, a novel C-met–targeting antibody drug conjugate, in patients with metastatic colorectal cancer (mCRC).
Authors: Carla Biesdorf de Almeida, Benjamin Engelhardt, Heiko Babel, Jesus D Badillo, Manish Sharma, John D. Powderly, Martha Raluca Neagu Aristide, Kevin Jay Freise, Sven Mensing, Apurvasena Parikh
Journal: Journal of Clinical Oncology (2024)

3030 Background: ABBV-400 is an antibody drug conjugate (ADC) consisting of a c-Met targeting antibody conjugated to a potent inhibitor of topoisomerase 1 (Top1) payload. ABBV-400 has shown encouraging activity and demonstrated tolerability of dosages up to 3.0 mg/kg Q3W as monotherapy in patients with advanced solid tumors in an ongoing phase 1 study (1). Dosage optimization is a critical aspect of oncology drug development and FDA Project Optimus has focused on reformulating the dosage selection paradigm for oncology products. The phase 1 study included a dose optimization phase in mCRC patients in which 3 doses were evaluated (1.6, 2.4 and 3.0 mg/kg Q3W) to determine the optimal dose for further development. Herein, exposure-response analyses are reported to determine optimal monotherapy dose in mCRC patients. Methods: Data across a range of doses (1.6 – 6.0 mg/kg Q3W) from the phase 1 study (NCT05029882) were used. Population pharmacokinetics (PK) and exposure-response (E-R) analyses were conducted to characterize ABBV-400 conjugate and unconjugated payload PK and the relationship between exposures and efficacy (objective response rate [ORR]) and safety (Grade (Gr) ≥ 3 neutropenia, anemia and thrombocytopenia) endpoints. Relative dose intensity (RDI) analysis was performed. Results: ABBV-400 conjugate and payload PK were adequately described by a combined multi-analyte population PK model with first order kinetics (n=204). ABBV-400 conjugate average concentration was a better predictor of response and showed that higher exposure correlated with higher probability of response (n=122 CRC, ORR, p &lt; 0.05) and safety events (n=204, Gr ≥ 3 neutropenia, anemia and thrombocytopenia, p &lt; 0.001). Dose intensity analyses showed greater number of dose reductions for 3 mg/kg Q3W with effective (actual) dose received of 2.6 mg/kg Q3W in mCRC patients. E-R analyses for safety and efficacy and dose intensity analyses in mCRC 3L+ patients indicate that both 2.4 and 3.0 mg/kg doses provided meaningful efficacy (ORR); while the 3.0 mg/kg dose may provide higher response rates, the 2.4 mg/kg Q3W dosing regimen provides an optimal balance of safety and efficacy compared to 3.0 mg/kg Q3W. Conclusions: Population PK, E-R for efficacy and safety and RDI analyses and totality of clinical data supported the selection of 2.4 mg/kg Q3W as optimal ABBV-400 monotherapy dose for further study in mCRC patients. 1. Sharma M, et al. ASCO 2023. Abstract 3015. Clinical trial information: NCT05029882 .
A phase 1/2 study of BDC-3042, a novel dectin-2 agonistic antibody, in patients with advanced cancers.
Authors: Mohamad Adham Salkeni, Andrae L. Vandross, Ecaterina Elena Dumbrava, Antonio Giordano, Christopher Chen, Justin Kenkel, Danlin Cai, Lu Xu, Michael N. Alonso, Shelley Ackerman, Tai Yu, Dawn E. Colburn, Edith A. Perez, Sharon Wilks
Journal: Journal of Clinical Oncology (2024)

TPS2695 Background: Tumor-associated macrophages (TAMs) are a major component of the immune infiltrate in most cancers and play a key role in establishing the immunosuppressive tumor microenvironment (TME) that enables tumor progression. However, TAMs are phenotypically plastic and have the potential to be reprogrammed into immunostimulatory cells that enhance innate and adaptive anti-tumor immunity. BDC-3042 is a novel agonistic antibody targeting an immune-activating receptor expressed on TAMs known as Dectin-2 ( CLEC6A) [1]. Dectin-2 is a C-type lectin receptor best known for its role in pathogen recognition and induction of protective immune responses against fungi and other microbes. We have previously demonstrated that Dectin-2 agonism stimulates pro-inflammatory cytokine secretion and antigen presentation by TAMs, resulting in robust CD8+ T cell-mediated anti-tumor immunity in syngeneic mouse models [2]. Elevated gene expression of Dectin-2 has been found in a wide range of solid tumor types compared to non-malignant tissues. Nonclinical studies with BDC-3042 have demonstrated its potential to reprogram TAMs and elicit anti-tumor activity as a novel immunotherapeutic approach for diverse human cancers [2]. A phase 1/2, first-in-human, dose-escalation and dose-expansion study of BDC-3042 as a single agent and in combination with a cemiplimab in subjects with advanced cancers has been initiated. Methods: This study is enrolling up to 185 patients with advanced cancers, including non-small cell lung cancer, melanoma, triple-negative breast cancer, renal cell carcinoma, colon cancer, head and neck cancer, and ovarian cancer. Primary objectives of the dose-escalation phase are to define safety and tolerability and to determine the recommended phase 2 dose (RP2D) of BDC-3042 as a monotherapy (Part 1) and in combination with cemiplimab (Part 2). The dose-expansion phase will evaluate preliminary anti-tumor activity of BDC-3042 monotherapy (Part 3) and with cemiplimab (Part 4). Secondary objectives will evaluate pharmacokinetic parameters and pharmacodynamic biomarkers in tumor tissue and in peripheral blood associated with drug exposure. Exploratory analyses will also be conducted to assess BDC-3042’s ability to reprogram TAMs and identify biomarkers associated with BDC-3042 biological activity and with cemiplimab. This study is being conducted in the US and is currently recruiting patients. 1. Kenkel J, et al. Cancer Res. 2023. 2. Kenkel J, et al. J Immunother Cancer. 2021. Clinical trial information: NCT06052852 .
An open-label, multicenter, phase I study of ATG-022 in patients with advanced/metastatic solid tumors (CLINCH).
Authors: Sarwan Bishnoi, Dan Cao, Shehara Ramyalini Mendis, Jim Coward, Jun Zhao, Hui Xie, Li Zheng
Journal: Journal of Clinical Oncology (2024)

3032 Background: Claudin 18.2 (CLDN 18.2) is a tumor associated antigen broadly expressed in gastric, pancreatic, and other solid tumors. ATG-022 is an antibody drug conjugate (ADC), consisting of a humanized monoclonal antibody that binds to CLDN 18.2 with high affinity of sub-nM grade and a conjugated linker-payload vc-MMAE. ATG-022 has displayed promising tumor growth inhibition activity both in vitro and in vivo. Methods: CLINCH is a phase I, multi-center, open-label, dose-finding study (NCT05718895) of ATG-022 in patients with advanced solid tumours. The study design includes a dose escalation phase, enrolling subjects with advanced/metastatic solid tumors, regardless of CLDN 18.2 expression, and a dose expansion phase which will enroll select advanced/metastatic solid tumors with CLDN 18.2-positive expression at the defined maximum tolerated dose and/or recommended Phase 2 dose to further evaluate the safety, tolerability, and efficacy of ATG-022. Other endpoints include pharmacokinetics (PK) and exploratory biomarkers of drug activity. In the dose escalation phase, ATG-022 is administered intravenously every 3 weeks (Q3W) at the starting dose of 0.3 mg/kg, followed by 0.9, 1.8, 2.4, 3.0, and 3.6 mg/kg Q3W using a modified 3+3 dose-escalation design. Efficacy assessments are evaluated per RECIST1.1 criteria. Results: As of 9 Oct 2023, 10 patients (pts) with advanced solid tumors have been enrolled to receive ATG-022 at a dose from 0.3 to 2.4 mg/kg. Median age was 59 years. Baseline ECOG scores were 0 (0 pts) and 1 (10 pts); 8 pts had stage IV disease. Three pts had received more than 3 prior lines of systemic therapy. Eight pts (80%) had ≥ 1 TRAEs; 1 pt (10%) had ≥ 1 Serious TRAEs; 3 (30%) pts had grade ≥ 3 TRAEs. The most common grade ≥ 3 TRAEs included nausea (30%), vomiting (30%) and decreased appetite (30%). No DLT was reported among the current dose levels. Among 7 pts with gastric cancer, 3 pts are confirmed to be CLDN 18.2 positive. One of these pts has maintained stable disease with tumor shrinkage for more than 6 months (treatment ongoing) at a dose of 0.9 mg/kg, demonstrating tolerability of ATG-022. One PR was observed in a gastric cancer pt (CLDN 18.2 expression to be determined) at the dosage of 1.8 mg/kg. It was noteworthy that a CR was seen in a gastric cancer pt dosed at 2.4 mg/kg, with negative CLDN 18.2 expression. PK analysis of ATG-022 from 0.3 to 2.4 mg/kg revealed that the exposure of total antibody, MMAE and ADC drug is increased as dose increased. No accumulation of ATG-022 was observed. Conclusions: ATG-022 demonstrated preliminary anti-tumor activity, tolerability, safety, as well as comparable PK properties at current dose levels. The high affinity of sub-nM grade of ATG-022 in pts with low CLDN 18.2 expression needs further investigation. The dose escalation is ongoing and updated data will be presented. Clinical trial information: NCT05718895 .