tbuckley/cabot-search huggingface dataset:
Combining nimotuzumab with PD-L1 inhibitors and chemotherapy to treat esophageal cancer: A retrospective study.
Authors: Size Chen, Yiguang Lin, Jiayi Dong, Minghan Song, Shao Lijuan
Journal: Journal of Clinical Oncology (2024)

e16072 Background: Combining immunotherapy with targeted therapy and/or chemotherapy has been shown to have superior clinical benefits in cancer treatment. The combination of immunotherapy, targeted therapy, and chemotherapy may be an option for esophageal cancer. This study assessed retrospectively the efficacy and safety of nimotuzumab combined with the PD-L 1 inhibitor and chemotherapy in the treatment of patients with esophageal cancer. Methods: All enrolled patients were from the First Affiliated Hospital of Guangdong Pharmaceutical University between September 2021 and August 2023. All patients received intravenous nimotuzumab (200 mg/w) combining with PD-L1 inhibitors (Tirelizumab; Caralizumab; Sintilimab; Pembrolizumab; Nivolumab and Penpulimab, 6 cycles in total) and chemotherapy (albumin paclitaxel 150mg/m2, cisplatin 25mg/m2, for 1-3 days per cycle, for a total of 6 cycles). The primary endpoint was overall survival (OS). Secondary endpoints consisted of the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety. Efficacy was assessed according to the criteria of RECIST 1.1 and while adverse events (AEs) were graded according to CTCAE 5.0. Following treatment, patients’ general condition, levels of lymphocytes, IL-6, hs-CRP, PCT, CYFRA21, NSE(E), and SCC were monitored regularly. Results: A total of18 patients diagnosed with EC were enrolled in the study. The majority of the patients were male (16/18), 17 (94.4%) patients diagnosed with esophageal squamous cell carcinoma. Lymphatic metastasis occurred in 13 (72.2%) patients and 5 (27.8%) patients experienced distant metastases. Six (33.3%) patients received radical surgery and five (27.8%) patients did not receive systematic antitumor therapy in the past. 17 (94.4%) patients diagnosed with esophageal squamous cell carcinoma (ESCC). No patient achieved complete response (CR) and 6 (33.3%) patients achieved partial response (PR). The ORR and DCR were 33.3% and 83.3%, respectively. The median OS was not achieved, the 12-month OS rate was 84.8%, 24-month OS rate was 74.2%. The median PFS was 7.9 months, the 12- and 24-month PFS rates were 44.0% and 36.7%, respectively. The incidence of Grade ≥ 3 AEs was 43.85%, including anemia (18.8%), lymphopenia (18.8%) and rash (6.3%). Conclusions: This combinational treatment regimen results in a significant improvement in OS compared to the combination of PD-L1 inhibitors and chemotherapy without increased AEs. Compared to other combinations of targeted drugs with PD-L1 inhibitors and chemotherapy, the use of nituzumab significantly prolonged mPFS and increased OS rates at 12 and 24 months.
Radiotherapy improved the efficacy of immunotherapy for advanced esophageal cancer.
Authors: Yicong Chen, Ruixuan Yu, Xiaojuan Zhou, Xiaoxiao Zeng, Yong Xu, Feng Peng, Bingwen Zou, Lin Zhou, Youling Gong, Jin Wang, Yongsheng Wang, Meijuan Huang, You Lu, Yongmei Liu
Journal: Journal of Clinical Oncology (2024)

e16063 Background: The development of immunotherapy has changed treatment methods for advanced esophageal cancer (EC).However, the efficacy of ICIs in advanced EC is not ideal, and the clinical research on the combination of ICIs and Radiotherapy(RT) in advanced EC remains insufficient. This study aimed to evaluate the effectiveness and safety of radiation in first-line immunotherapy for advanced EC. Methods: We conducted 201 advanced EC patients who received first-line ICIs in West China Hospital. The enrolled patients were divided into 2 groups based on whether they received radiation therapy. Results: The analysis included data from 201 patients. The radiotherapy (RT) group had 103 patients (51.2%), whereas the non-radiotherapy (NRT) group included 98 individuals (48.8%). The RT sites include esophagus lesions (83, 80.6%), metastatic lymph nodes (11, 10.7%), liver metastases (4, 3.9%), bone metastases (2, 1.9%), brain metastases (2, 1.9%), lung metastases(1, 0.97%). The median radiation dose was 50.4 Gy (range, 12-68). The RT group had a median OS of 22.8 months (95% CI, 17.8-NA), which was longer than the NRT group's 14.6 months (95% CI, 12.8-26.5) (p = 0.038). And the median PFS was 12.9 months (95% CI, 11.2-14.0) in the RT group versus 7.3 months (95% CI, 6.3-9.7) in the NRT group (p = 0.006). Patients in the RT group had a higher disease control rate (DCR) (99.0% vs. 76.5%, P &lt; 0.001). However, a higher proportion of patients in the RT group developed grade 3-4 myelosuppression (37.86% V.S. 20.20%, P = 0.006), and there was no significant difference in the other AEs. Conclusions: In the first-line immunotherapy for advanced esophageal cancer, radiotherapy has been attributed to improved survival with tolerable toxicity.
Triple combination treatment of trastuzumab, chemotherapy and immune checkpoint inhibitor in HER2 positive unresectable, locally advanced, metastatic gastric and esophageal adenocarcinoma: A systematic review and meta-analysis.
Authors: Lorenz Fort Estrada Revillas, Carlos Dy, John Kelvin Lalusis
Journal: Journal of Clinical Oncology (2024)

e16071 Background: The current standard of care for unresectable, locally advanced or metastatic HER2 positive gastric, esophageal and gastroesophageal junction adenocarcinomas is the combination of the anti HER 2 antibody trastuzumab and cytotoxic chemotherapy. In recent years, the addition of immune checkpoint inhibitors to this combination has been studied to determine if it can improve clinical outcomes for this disease. This systematic review and meta-analysis evaluated high-quality data from clinical trials to determine the role and efficacy of this triple combination treatment. Methods: A systematic search of English-language articles on PubMed, Cochrane and Google scholar was done to identify randomized trials (RCTs) investigating the use of triple combination treatment of anti-Her 2 antibody, chemotherapy and immune checkpoint inhibitor in the treatment of unresectable, locally advanced, or metastatic HER2 overexpression positive gastric, esophageal and gastroesophageal junction adenocarcinoma. Quality of the studies was assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2). Inverse variance was the statistical method used with random effects as the analysis model in the production of the Forest plot and calculation of risk ratio (RR) at 95% confidence intervals (CI). Results: Four (4) RCTs (N = 866) were included for quality assessment and data extraction. Two (2) of these RCTs (N = 80) were single arm studies which both showed favorable outcomes in terms of objective response rate and progression free survival. The two (2) other RCTS (N = 786), each had two arms (triple regimen versus comparator) and were used in the meta-analysis. Risk of bias was low and heterogeneity was low (I 2 below 50%). Pooled results showed that in patients given triple combination regimen, there is statistically significant improvement in progression free survival (RR 1.55 95% CI 1.20-2.00, p 0.0007). There is also an increase in overall response rate in favor of the triple combination regimen, albeit not statistically significant (RR 1.31 95% CI 0.99-1.74, p = 0.06). Conclusions: The addition of an immune checkpoint inhibitor to the current standard of care of anti Her 2 antibody and chemotherapy provides meaningful results in terms of tumor response and progression free survival in Her 2 positive locally advanced or metastatic gastric and esophageal adenocarcinomas. More robust trials, and data on overall survival supporting the use of this triple regimen may help re-shape the current standard of care for this disease.
Efficacy, safety and DNA methylation analysis of cadonilimab combined with taxane and cisplatin as the first-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC): An open-label, multicenter phase II trial– Updated results from AK104-IIT-014.
Authors: Wang Qu, Jing Gao, Bo Zhang, Yun Liu, Yijia Guo, Mudan Yang, Jing Huang
Journal: Journal of Clinical Oncology (2024)

e16064 Background: Immune checkpoint inhibitors combined with chemotherapy has become the current first-line standard treatment for advanced ESCC, while still having a lot of room for improvements in objective responses and survival. Cadonilimab, a bispecific antibody simultaneously targeting PD-1 and CTLA-4, may further boost anti-tumour activity with a satisfied safety profile. Here, we present the updated data for the safety and efficacy of Cadonilimab combination therapy as the first-line treatment in advanced ESCC. Methods: Treatment-naïve patients (pts) with unresectable locally advanced or metastatic ESCC were eligible for inclusion. Cadonilimab (10mg/kg, iv, d1, q3w) combined with paclitaxel or nab-paclitaxel (175 mg/m 2 , iv, d1, q3w) and cisplatin (65 to 75 mg/m 2 , iv, d1, q3w) were administrated for up to 6 cycles, then Cadonilimab (10mg/kg, iv, d1, q3w) monotherapy continued as maintenance until progressive disease or unacceptable toxicity, with a maximum of 24 months. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety. Plasma cell-free DNA samples were collected before and after treatment and prepared for DNA methylation level sequencing. Results: At updated analysis (cut-off: February 5, 2024), 35 pts were enrolled with a median age of 61 years (range 44-75), 82.9% were male, 57.1% had PD-L1 CPS&lt;10 and 88.6% had distant metastases. In the efficacy-evaluable population (n = 29), 5 pts reached complete response (CR), 21 pts had partial response (PR) and 3 pts had stable disease (SD). The ORR was 89.7% (95%Cl: 71.5%-97.3%) and the DCR was 100.0% (95%Cl: 85.4%-100.0%). Among evaluable pts with PD-L1 CPS≥10 and PD-L1 CPS&lt;10, the ORR were 100.0% (12/12) and 81.3% (13/16), respectively. SEPT9 methylation was significantly higher in patients with CR or PR compared to patients with SD (33.28% vs 3.87%, p &lt; 0.001). The median PFS and OS was still not reached. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 9 (25.7%) pts. The most common TRAEs were neutropenia (17.1%), leukopenia (5.7%) and hyponatremia (5.7%). Immune-related adverse events were observed in 9 pts (25.7%). Three pts (8.6%) suffered from serious adverse events, and no grade 5 TRAEs or death were observed. Conclusions: The updated results suggested that bispecific antibody AK104 combined with taxane and cisplatin as first-line treatment showed promising anti-tumor activity and manageable safety in patients with advanced ESCC. DNA methylation level might be a potential biomarker for guiding patient outcomes. Follow-up is ongoing for survival analysis. Clinical trial information: NCT05522894 .
An open-label, multicenter phase 1 study to characterize safety, tolerability, preliminary antitumor activity, pharmacokinetics, and pharmacodynamics of VIP943 monotherapy in patients with advanced CD123+ hematologic malignancies.
Authors: Stephen Anthony Strickland, Emily K. Curran, Omer Hassan Jamy, Mary-Elizabeth Percival, Amy J. Johnson, Joseph Birkett, Xin Huang, Melanie M. Frigault, Hans-georg Lerchen, Beatrix Stelte-Ludwig, Tasheda Navarro, Jim Peck, Wyatt Gross, Raquel Izumi, Ahmed M. Hamdy, Naval Guastad Daver
Journal: Journal of Clinical Oncology (2024)

TPS3167 Background: VIP943 is an anti-CD123 antibody-drug conjugate (ADC) with a unique linker cleaved only by legumain and a novel kinesin spindle protein inhibitor payload. The linker-payload was engineered to increase the therapeutic index thereby improving efficacy and reducing severe toxicities compared with current ADCs. In an in vivo MOLM-13 model, VIP943 had statistically significant (p &lt;0.001) improvement in tumor growth inhibition compared with the only ADC approved for the treatment of acute myeloid leukemia (AML), gemtuzumab ozogamicin (GO). In a nonhuman primate (NHP) single dose toxicology study, VIP943 (20 mg/kg) showed no signs of toxicity as measured by hematology, serum chemistry and survival. In contrast, NHP treated with a single dose of GO (3 mg/kg) had significant toxicity including death and mandatory euthanasia. The single-dose toxicity of GO was ameliorated by substituting the VIP943 proprietary linker and payload on an anti-CD33 antibody (3 mg/kg) as measured by hematology, serum chemistry and survival. (1,2). Methods: This trial in progress (NCT06034275) is an open-label, multicenter, Phase 1, first-in-human (FIH), dose-escalation and dose-optimization study of VIP943 in subjects with relapsed or refractory CD123+ hematologic malignancies including AML, myelodysplastic syndrome, and B-cell acute lymphoblastic leukemia. A cycle of VIP943 treatment is 28 days of once weekly intravenous infusions with no pause between cycles. The dose-escalation portion of this study follows a standard 3+3 design. Dose escalation decisions will be made by the safety review committee, and decisions will be based on the incidence of dose-limiting toxicities (DLTs). Based on FDA guidance, a dose-optimization portion of this study will randomize subjects into ≥2 dose cohorts to derive a recommended dose range for Phase 2. The study will also characterize the pharmacokinetics of VIP943 and its components and explore potential biologic activity by assessing pharmacodynamic/exploratory biomarkers, and antitumor activity using standard response criteria. As this is a FIH study, only subjects with CD123+ hematologic malignancies who have exhausted all available therapies or are not fit for standard of care can be enrolled. The results from this study will form the basis for decisions for future studies. Enrollment for cohorts 1 (no DLTs) and 2 (safety review ongoing) has completed. 1. Stelte-Ludwig et al ASH 2022. 2. Stelte-Ludwig et al ASH 2023. Clinical trial information: NCT06034275 .
Impact of rituximab maintenance on survival of patients with mantle cell lymphoma: A north Indian tertiary care center experience.
Authors: Soumyadeep Datta, Ajay Gogia, Naveet Wig, Hari Krishna Raju Sagiraju, ATUL SHARMA, Saumyaranjan Mallick, Ritu Gupta
Journal: Journal of Clinical Oncology (2024)

e19047 Background: Mantle cell lymphoma (MCL) is an aggressive variant of non-Hodgkin lymphoma. Indian data is scarce owing to its rarity in south-east Asia. Till now, studies have not shown overall survival benefit with rituximab maintenance (RM). Our study aims to assess if RM improves overall survival of MCL patients. Methods: We retrospectively analysed clinicopathological data of 90 transplant-ineligible MCL patients treated between January’2013-December’2023 at Institute Rotary Cancer Hospital - All India Institute of Medical Sciences, New Delhi, India. Rituximab-based induction chemotherapy was used in all patients as per institutional protocol. RM was used in twenty-eight (31.0%) patients due to financial constraints. Primary outcome was overall survival (OS). Secondary outcomes were event free survival (EFS) and factors affecting OS, EFS. OS was defined as time from treatment initiation to demise from any cause or last follow-up. EFS was defined as time from treatment initiation to disease progression or relapse or demise from any cause. Response was assessed by modified Cheson’s lymphoma response evaluation criteria. STATA 13.0 was used to assess survival by Kaplan-Meier analysis and log rank test. Factors affecting survival were assessed by multivariate analysis (Cox proportional hazards model) and expressed as adjusted hazard ratio (aHR). p value &lt; 0.05 defined statistical significance. Results: Median age was sixty years; male-female ratio 3:1. Thirty-five (39.0%) had one or more co-morbidities, 79(88.0%) generalised lymphadenopathy, 72(80.0%) extra-nodal involvement, 49(54.0%) B symptoms, 84(93.0%) advanced stage (III/IV), 49(54.0%) high risk MCL international prognostic index (MIPI). Clinical and tumor characteristics, response rates after initial induction were similar in both maintenance and non-maintenance groups. Overall, 52(58.0%) patients were alive with median follow-up of 63.0 months (inter-quartile range 37.0-90.0 months). Median OS was 37.5 months in non-maintenance group and did not reach in maintenance group. Estimated 1.0-, 2.0, 3.0-year OS were 100.0%, 91.0%, 81.0% vs 75.0%, 63.0%, 55.0% respectively in maintenance vs non-maintenance group. RM was significantly associated with better OS [aHR (95% confidence interval): 0.31 (0.13-0.75), p=0.01]. Advanced stage, Eastern Co-operative Oncology Group performance status (ECOG PS) ≥2 at presentation were also significant factors for poor OS. Median EFS was significantly lower in non-maintenance group [14.0 vs 42.5 months; aHR (95% confidence interval): 0.34 (0.18-0.64), p=0.001]. Advanced stage, anemia, high risk MIPI at presentation were also significant factors for poor EFS. Conclusions: This was the first study from south-east Asia demonstrating impact of rituximab maintenance in MCL. Rituximab maintenance significantly improved OS and EFS of MCL patients.
Revealing heterogeneity in chronic lymphocytic leukemia: AI-driven insights into aggressive and indolent disease subtypes.
Authors: Bessi Qorri, Joseph Geraci, Mike Tsay, Christian Cumbaa, Larry Alphs, Luca Pani
Journal: Journal of Clinical Oncology (2024)

e19029 Background: Chronic lymphocytic leukemia (CLL) exhibits a broad spectrum of clinical behaviors, from indolent courses requiring minimal intervention to aggressive forms demanding immediate treatment. The underlying heterogeneity of CLL poses significant challenges in predicting disease progression and tailoring patient-specific therapeutic strategies. Leveraging advanced and novel artificial intelligence (AI) and machine learning (ML) methodologies, our study aims to dissect the complexity of CLL, focusing on the identification and characterization of biomarkers that differentiate aggressive and indolent disease forms. Methods: The NetraAI is a priorietaryAI/ML system that is also being utilized in a research collaboration at a leading American oncology institute (not disclosed) that integrates machine intelligence, augmented intelligence, and an agent that interacts with AI-derived patient representations. This system was designed to learn from datasets with a small number of samples and many independent variables. This system operates by generating hypotheses in the form of interactive representations of patient populations that reveal heterogeneity along with statistically significant driving factors. Finally, an automated agent called AutoPlay interacts with these representations and generates an accounting of all variables, subpopulations of samples, and it also generates a human readable perspective on what was discovered by the data set. Results: We applied the NetraAI to a CLL dataset and used it to refine the analysis and interpretation of the corresponding transcriptomic data (GSE39411). Significantly lower levels of FADS3, GSDME, LPL, IMMT, NMB, and AEBP1 and higher expressions of COBLL1, P2RY1R, PDE8A, SYNE2, and FCRL3 were identified as hallmarks of indolent CLL, suggesting these markers could inform less aggressive disease management strategies. Furthermore, within a total of 104 CLL samples, we uncovered two distinct subpopulations within aggressive CLL, delineated by unique genetic markers. Group A, encompassing 31 aggressive CLL samples is predominantly characterized by the expression of lipoprotein lipase (LPL), while Group B, comprising 22/23 aggressive samples, is characterized by ZBTB20 and SYNE2. Our poster will also provide glimpses into a more refined heterogeneity that emerged from the analysis. Our results not only underscore the heterogeneity within aggressive CLL, but also highlights the potential for these markers to guide prognostic assessments and therapeutic decisions. Conclusions: This study not only advances our understanding of CLL heterogeneity, but also sets the stage for the development of more personalized and effective treatment modalities. By identifying drivers of disease aggression and indolence, we pave the way for targeted therapies that could significantly improve patient outcomes in CLL.
Effects and outcomes of tumor lysis syndrome in patients admitted with Hodgkin and non-Hodgkin lymphoma: A National Inpatient Sample study (2019-2020).
Authors: Mrunanjali Gaddam, Rabia Iqbal, Jayalekshmi Jayakumar, Manasa Ginjupalli, Bhavyakumar Vachhani, Sujana Sanka, Priya Thanneeru, Rohit Sekandlapuram, Ankushi Sanghvi, Priya Hotwani, Dhairya Nanavaty, Vikash Kumar, Surbhi Singh, Ana Colon Ramos, Jincy Clement
Journal: Journal of Clinical Oncology (2024)

e19032 Background: Tumor Lysis Syndrome (TLS) is a life-threatening oncologic emergency. The newer advancement in therapeutic approaches in oncology has widened the range of malignancies associated with TLS. A lot of literature on the incidence of TLS in various solid malignancies exists. However, the effects of TLS on hematological malignancies, especially Hodgkin’s Lymphoma (HL) and Non-Hodgkin’s Lymphoma (NHL) have rarely been analyzed. Our study aims to identify the impact of TLS in patients hospitalized with HL and NHL and draw a comparison between HL and NHL. Methods: We analyzed the National Inpatient Sample database from 2019 - 2020 to identify patients &gt; 18 years old with a primary diagnosis of HL and NHL. We compared the TLS prevalence and all-cause in-hospital mortality, length of hospital stay (LOS), and total costs in patients admitted with HL and compared it with NHL. Categorical variables were compared using the chi-square test, and the t-test compared continuous variables. Multivariable regression analyses were performed adjusting for demographics, hospital-level characteristics, and relevant comorbidities. Results: Among 24,550 Hodgkin’s Lymphoma (HL) hospitalizations and 108,060 Non-Hodgkin’s Lymphoma (NHL) hospitalizations, TLS was diagnosed in 0.69% of HL patients and 0.89% of NHL patients. In-hospital mortality was significantly higher in both HL (44.1%) and NHL (28.3%) patients with TLS compared to those without TLS (HL: 4.5%, NHL: 5.1%). Multivariate regression analysis revealed that TLS presence increased the chance of mortality among both HL (OR 17.9) and NHL (OR 7.3) patients. TLS also significantly impacted secondary outcomes including Acute Kidney Injury (AKI) and Hyperkalemia in both HL and NHL patients. No statistically significant differences were found in the odds of cardiac arrhythmias between HL and NHL patients with TLS (Table). TLS was associated with longer Length of Stay and higher total hospital costs in both HL and NHL patients compared to those without TLS. Conclusions: TLS is significantly associated with increased mortality in patients with HL and NHL, more in HL compared to NHL. In patients with HL, and NHL, TLS is an independent risk factor for in-patient mortality, the longer LOS, and the total cost, thereby incurring an increased burden on healthcare resources. Our study aims to highlight the need for greater vigilance in this vulnerable group when TLS occurs. [Table: see text]