Exploration of targeted anti-tumor therapy最新文献

{"title":"Eosinophil cytolysis with or without ETosis in four cases of human gastric cancer: a comparative ultrastructural study.","authors":"Rosario Caruso, Valerio Caruso, Luciana Rigoli","doi":"10.37349/etat.2025.1002309","DOIUrl":"https://doi.org/10.37349/etat.2025.1002309","url":null,"abstract":"<p><p>The ultrastructural morphology of eosinophil cytolysis and extracellular trap cell death (ETosis) has predominantly been examined in non-neoplastic eosinophil-associated diseases, with a limited investigation in neoplasms. This current electron microscopy study examined the ultrastructural characteristics of eosinophil cytolysis and ETosis across four distinct gastric cancer cases: three cases (cases 1-3) exhibited non-ETotic cytolysis, while one case (case 4) presented eosinophils at various stages of ETosis. In cases 1-3, eosinophil non-ETotic cytolysis was characterized by localized plasma membrane disruption, the presence of free extracellular granules (FEGs), and the maintenance of a round or oval nuclear lobe profile. In case 4, eosinophils were observed in progressive stages of ETosis, arbitrarily subdivided into early, intermediate, and advanced. Although early ETosis and non-ETotic cytolysis exhibited overlapping ultrastructural features, chromatin decondensation and nuclear envelope enlargement were more pronounced in early ETosis. Nuclear envelope disruption, loss of the round or oval nuclear lobe profile (intermediate stage), extracellular DNA trap deposition, and the appearance of Charcot-Leyden crystals (advanced stage) were all distinctive features of ETosis. The findings of this case report confirm previous observations of eosinophil cytolysis with or without ETosis in non-neoplastic diseases and extend them to advanced gastric carcinoma. Since Charcot-Leyden crystals were only seen in case 4, their correlation with ETosis was further supported. In gastric cancer, the release of FEGs during non-ETotic cytolysis and the release of both FEGs and DNA traps during ETotic cytolysis may contribute to the formation of an antitumor microenvironment.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002309"},"PeriodicalIF":0.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12022494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoimmunotherapy: the smart trooper for cancer therapy.","authors":"Suphiya Parveen, Dhanshree Vikrant Konde, Safal Kumar Paikray, Nigam Sekhar Tripathy, Liza Sahoo, Himansu Bhusan Samal, Fahima Dilnawaz","doi":"10.37349/etat.2025.1002308","DOIUrl":"https://doi.org/10.37349/etat.2025.1002308","url":null,"abstract":"<p><p>Immunotherapy has gathered significant attention and is now a widely used cancer treatment that uses the body's immune system to fight cancer. Despite initial successes, its broader clinical application is hindered by limitations such as heterogeneity in patient response and challenges associated with the tumor immune microenvironment. Recent advancements in nanotechnology have offered innovative solutions to these barriers, providing significant enhancements to cancer immunotherapy. Nanotechnology-based approaches exhibit multifaceted mechanisms, including effective anti-tumor immune responses during tumorigenesis and overcoming immune suppression mechanisms to improve immune defense capacity. Nanomedicines, including nanoparticle-based vaccines, liposomes, immune modulators, and gene delivery systems, have demonstrated the ability to activate immune responses, modulate tumor microenvironments, and target specific immune cells. Success metrics in preclinical and early clinical studies, such as improved survival rates, enhanced tumor regression, and elevated immune activation indices, highlight the promise of these technologies. Despite these achievements, several challenges remain, including scaling up manufacturing, addressing off-target effects, and navigating regulatory complexities. The review emphasizes the need for interdisciplinary approaches to address these barriers, ensuring broader clinical adoption. It also provides insights into interdisciplinary approaches, advancements, and the transformative potential of nano-immunotherapy and promising results in checkpoint inhibitor delivery, nanoparticle-mediated photothermal therapy, immunomodulation as well as inhibition by nanoparticles and cancer vaccines.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002308"},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11996242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategies to overcome resistance to enfortumab vedotin and pembrolizumab for patients with urothelial carcinoma: harnessing present knowledge for future advances.","authors":"Albert Jang, Jason R Brown","doi":"10.37349/etat.2025.1002307","DOIUrl":"https://doi.org/10.37349/etat.2025.1002307","url":null,"abstract":"<p><p>The combination of enfortumab vedotin and pembrolizumab (EVP) has been recently approved for patients with locally advanced and metastatic urothelial carcinoma. This combination showed a higher objective response rate and superior progression-free survival and overall survival over traditional platinum-based chemotherapy in the frontline setting in the pivotal EV-302 trial. Despite the success, a subset of patients has primary refractory disease, and another subset will develop secondary resistance over time. Resistance to enfortumab vedotin may include the downregulation of nectin-4 expression to minimize antibody binding, upregulation of efflux pumps against the toxin, or direct resistance by the tubulin against the toxin. Resistance to pembrolizumab includes several methods to downregulate the immune system. Additionally, the type of histology of the urothelial carcinoma likely plays an important role in resisting EVP. This review summarizes these possible mechanisms of primary and secondary resistance, potential biomarkers predictive of response and resistance, and methods to overcome the resistance to EVP.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002307"},"PeriodicalIF":0.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring recent advances in signaling pathways and hallmarks of uveal melanoma: a comprehensive review.","authors":"Majid Banimohammad, Parsa Khalafi, Danial Gholamin, Zahra Bangaleh, Nahid Akhtar, Abhishikt David Solomon, Pranav Kumar Prabhakar, Samira Sanami, Ajit Prakash, Hamidreza Pazoki-Toroudi","doi":"10.37349/etat.2025.1002306","DOIUrl":"10.37349/etat.2025.1002306","url":null,"abstract":"<p><p>The purpose of this review was to provide a comprehensive review of the latest insights on the pathogenesis of uveal melanoma (UM) and its intracellular pathways. This article covers the epidemiology of UM, racial predispositions, cytogenetic and chromosomal alterations, gene mutations, key defective pathways, and their underlying mechanisms, as well as the application of hallmarks of cancer to UM. A key knowledge gap remains in identifying the most effective targeted therapy and determining the central pathway linking multiple signaling networks. UM is a malignant tumor arising from uveal melanocytes, predominantly affecting the choroid, with both genetic and epigenetic contributors. Key cytogenetic alterations include monosomy 3, chromosome 6p gain, chromosome 1p loss, and chromosome 8q gain. The most important UM-related signaling pathways are RAS/MAPK, PI3K/Akt/mTOR, Hippo-YAP, retinoblastoma (Rb), and p53 pathways. In the RAS/MAPK pathway, <i>GNAQ</i>/<i>GNA11</i> mutations occur which account for more than 80% of UM cases. The PI3K/Akt/mTOR pathway promotes cyclin D1 overexpression and MDM2 upregulation, leading to p53 pathway inhibition. <i>GNAQ</i>/<i>GNA11</i> mutations activate YAP via the Trio-RhoGTPase/RhoA/Rac1 signaling circuit in the Hippo-YAP pathway. Rb pathway dysregulation results from cyclin D1 overexpression or cyclin-dependent kinase inhibitor (CDKI) inactivation. In the p53 pathway, UM is characterized by <i>p53</i> mutations, MDM2 overexpression, and Bcl-2 deregulation. Eventually, the ARF-MDM2 axis serves as a critical link between the RAS and p53 pathways. Hallmarks of cancer, such as evasion of growth suppression and self-sufficiency in growth signals, are also evident in UM. Genetic and epigenetic alterations, including <i>NSB1</i>, <i>MDM2</i> and <i>CCND1</i> amplification, and <i>BAP1</i> mutations, play pivotal roles in UM pathobiology. Thus, UM exhibits a multifactorial pathology. By consolidating key mechanisms underlying UM pathogenesis, this review provides a comprehensive perspective on the involved pathways, offering insights that may facilitate the development of effective therapeutic strategies.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002306"},"PeriodicalIF":0.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world outcomes of lenvatinib plus pembrolizumab in intermediate- and poor-risk metastatic renal cell carcinoma.","authors":"Ilya Tsimafeyeu, Alexander Sultanbaev, Daria Dubovichenko, Makhabbat Murzalina, Alexander Volkov, Rashida Orlova, Igor Utyashev, Georgy Malina, Mark Gluzman","doi":"10.37349/etat.2025.1002305","DOIUrl":"10.37349/etat.2025.1002305","url":null,"abstract":"<p><p>The combination of lenvatinib and pembrolizumab (Len + Pembro) demonstrated significant efficacy in the phase 3 CLEAR study for metastatic renal cell carcinoma (RCC). However, poor-risk patients represented only a small proportion of the trial population. This multicenter retrospective cohort study assessed the real-world efficacy and safety of Len + Pembro in patients with clear-cell metastatic RCC and intermediate or poor International Metastatic RCC Database Consortium risk. Outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Sixty patients were analyzed, with a median age of 56 years. Poor risk was identified in 53% of patients, and 90% had metastases to ≥ 2 organs. ORR was 48.33%, disease control rate was 86.7%, and median PFS was 19.0 months. Grade ≥ 3 adverse events occurred in 25% of patients, with 33.3% requiring lenvatinib dose reductions. Lenvatinib plus pembrolizumab demonstrated robust efficacy and a manageable safety profile in a real-world population with advanced disease and poor-risk features, consistent with outcomes reported in clinical trials.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002305"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key immune cells and their crosstalk in the tumor microenvironment of bladder cancer: insights for innovative therapies.","authors":"Anna Di Spirito, Sahar Balkhi, Veronica Vivona, Lorenzo Mortara","doi":"10.37349/etat.2025.1002304","DOIUrl":"10.37349/etat.2025.1002304","url":null,"abstract":"<p><p>Bladder cancer (BC) is a heterogeneous disease associated with high mortality if not diagnosed early. BC is classified into non-muscle-invasive BC (NMIBC) and muscle-invasive BC (MIBC), with MIBC linked to poor systemic therapy response and high recurrence rates. Current treatments include transurethral resection with Bacillus Calmette-Guérin (BCG) therapy for NMIBC and radical cystectomy with chemotherapy and/or immunotherapy for MIBC. The tumor microenvironment (TME) plays a critical role in cancer progression, metastasis, and therapeutic efficacy. A comprehensive understanding of the TME's complex interactions holds substantial translational significance for developing innovative treatments. The TME can contribute to therapeutic resistance, particularly in immune checkpoint inhibitor (ICI) therapies, where resistance arises from tumor-intrinsic changes or extrinsic TME factors. Recent advancements in immunotherapy highlight the importance of translational research to address these challenges. Strategies to overcome resistance focus on remodeling the TME to transform immunologically \"cold\" tumors, which lack immune cell infiltration, into \"hot\" tumors that respond better to immunotherapy. These strategies involve disrupting cancer-microenvironment interactions, inhibiting angiogenesis, and modulating immune components to enhance anti-tumor responses. Key mechanisms include cytokine involvement [e.g., interleukin-6 (IL-6)], phenotypic alterations in macrophages and natural killer (NK) cells, and the plasticity of cancer-associated fibroblasts (CAFs). Identifying potential therapeutic targets within the TME can improve outcomes for MIBC patients. This review emphasizes the TME's complexity and its impact on guiding novel therapeutic approaches, offering hope for better survival in MIBC.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002304"},"PeriodicalIF":0.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"State-of-the-art photodynamic therapy for malignant gliomas: innovations in photosensitizers and combined therapeutic approaches.","authors":"Bruno A Cesca, Kali Pellicer San Martin, Matías D Caverzan, Paula M Oliveda, Luis E Ibarra","doi":"10.37349/etat.2025.1002303","DOIUrl":"10.37349/etat.2025.1002303","url":null,"abstract":"<p><p>Glioblastoma (GBM), the most aggressive and lethal primary brain tumor, poses a significant therapeutic challenge due to its highly invasive nature and resistance to conventional therapies, including surgery, chemotherapy, and radiotherapy. Despite advances in standard treatments, patient survival remains limited, requiring the exploration of innovative strategies. Photodynamic therapy (PDT) has emerged as a promising approach, leveraging light-sensitive photosensitizers (PSs), molecular oxygen, and specific light wavelengths to generate reactive oxygen species (ROS) that selectively induce tumor cell death. Originally developed for skin cancer, PDT has evolved to target more complex malignancies, including GBM. The refinement of second- and third-generation PS, coupled with advancements in nanotechnology, has significantly improved PDT's selectivity, bioavailability, and therapeutic efficacy. Moreover, the combination of PDT with chemotherapy, targeted therapy, and immunotherapy, among other therapeutic modalities, has shown potential in enhancing therapeutic outcomes. This review provides a comprehensive analysis of the preclinical and clinical applications of PDT in GBM, detailing its mechanisms of action, the evolution of PS, and novel combinatory strategies that optimize treatment efficacy. However, several challenges remain, including overcoming GBM-associated hypoxia, enhancing PS delivery across the blood-brain barrier, and mitigating tumor resistance mechanisms. The integration of PDT with molecular and genetic insight, alongside cutting-edge nanotechnology-based delivery systems, may revolutionize GBM treatment, offering new prospects for improved patient survival and quality of life.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002303"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in adoptive cell therapies in small cell lung cancer.","authors":"Eljie Isaak Bragasin, Justin Cheng, Lauren Ford, Darin Poei, Sana Ali, Robert Hsu","doi":"10.37349/etat.2025.1002302","DOIUrl":"10.37349/etat.2025.1002302","url":null,"abstract":"<p><p>Small cell lung cancer (SCLC) is an aggressive tumor characterized by early metastasis and resistance to treatment, making it a prime target for therapeutic investigation. The current standard of care for frontline treatment involves a combination of chemotherapeutic agents and immune checkpoint inhibitors (ICIs), though durability of response remains limited. The genetic heterogeneity of SCLC also complicates the development of new therapeutic options. Adoptive cell therapies show promise by targeting specific mutations in order to increase efficacy and minimize toxicity. There has been significant investigation in three therapeutic classes for application towards SCLC: antibody drug conjugates (ADCs), bispecific T-cell engagers (BiTEs), and chimeric antigen receptor (CAR)-T cell therapies. This review summarizes the recent advances and challenges in the development of adoptive cell therapies. Genetic targets such as delta-like ligand 3 (DLL3), trophoblast cell surface antigen 2 (Trop2), B7-H3 (CD276), gangliosides disialoganglioside GD2 (GD2) and ganglioside GM2 (GM2) have been found to be expressed in SCLC, which makes them prime targets for therapy development. While investigated therapies such as rovalpituzumab tesirine (Rova-T) have failed, several insights from these trials have led to the development of compelling new agents such as sacituzumab govitecan (SG), ifinatamab deruxtecan (I-DXd), tarlatamab, and DLL3-targeted CAR-T cells. Advancing development of molecular testing and improving targeted approaches remain integral to pushing forward the progress of adoptive cell therapies in SCLC.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002302"},"PeriodicalIF":0.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bladder cancer biomarkers.","authors":"Dominik Godlewski, Dorota Bartusik-Aebisher, Sara Czech, Jakub Szpara, David Aebisher","doi":"10.37349/etat.2025.1002301","DOIUrl":"10.37349/etat.2025.1002301","url":null,"abstract":"<p><p>Bladder cancer (BCa) is among the most frequently diagnosed urinary tract cancers, characterized by a high recurrence rate and significant clinical heterogeneity. Effective diagnosis and treatment of BCa demand continuous advancements in medical technologies, particularly given the limitations of classical methods such as cystoscopy and urine cytology. A comprehensive search of PubMed and Web of Science was conducted using relevant keywords to structure this narrative review. Additionally, specialist journals were reviewed. Only articles in English were included, with selection based on titles, abstracts, and availability of full texts. In recent years, biomarkers have emerged as crucial tools complementing traditional techniques, providing more precise, sensitive, and non-invasive methods for early detection, prognosis, and monitoring treatment response in BCa. Molecular, genetic, and protein biomarkers enable a deeper understanding of BCa biology, creating opportunities for personalized therapy tailored to individual patient needs. However, despite their potential, certain challenges remain, including standardization, validation, and integration into routine clinical practice. This review highlights recent advancements in BCa biomarkers and their transformative potential in oncological care. It underscores the importance of incorporating these innovations to refine diagnostic and therapeutic approaches, ultimately improving patient outcomes. Modern diagnostic and prognostic tools for BCa can enhance treatment outcomes by enabling early disease detection and reducing recurrence risks. This progress promises to improve patients' quality of life by minimizing disease burden and fostering effective, tailored care strategies.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002301"},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic review and meta-analysis of phase III randomized controlled trials to assess the risk of pneumonia, URTIs, and VTE in multiple myeloma patients treated with isatuximab.","authors":"Daniel Thomas Jones, Hazem Aboaid, Ramaditya Srinivasmurthy, Kevin Nguyen, Rishi Kumar Nanda, Jason Ta, Benjamin Tzer-Ming Chuang, Yin Mon Myat, Aishwarya Hanspal, Kyaw Zin Thein, Thura Win Htut","doi":"10.37349/etat.2025.1002300","DOIUrl":"10.37349/etat.2025.1002300","url":null,"abstract":"<p><strong>Background: </strong>Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of malignant plasma cells in the bone marrow, constituting approximately 13% of all hematologic malignancies. Isatuximab is a monoclonal antibody targeting the CD38 protein on myeloma cells, causing cell death through various immune-mediated mechanisms. Clinical trials have shown that adding isatuximab to standard regimens for MM significantly enhances efficacy but introduces some notable toxicities. The purpose of this study is to determine the risk of pneumonia, upper respiratory tract infections (URTIs), and venous thromboembolism (VTE) in patients with MM treated with isatuximab.</p><p><strong>Methods: </strong>We conducted a comprehensive literature search using Medline, Embase, and Cochrane databases from inception through July 22nd, 2024. Phase III randomized controlled trials (RCTs) utilizing isatuximab in newly diagnosed MM (NDMM) and relapsed and refractory MM (RRMM) reporting pneumonia, URTIs, and VTE as adverse events were included. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q-statistic. Random effects model was applied.</p><p><strong>Results: </strong>A total of 1,044 patients from three phase III RCTs (ICARIA-MM, IKEMA, IMROZ) were included for pneumonia and URTI analysis, while 1,403 patients from three trials (IKEMA, IMROZ, GMMG-HD7) were included for VTE evaluation. The incidence of any-grade pneumonia was higher in the isatuximab group (30.1% vs. 23.2%; RR, 1.31; 95% CI 1.06-1.61; <i>P</i> = 0.01), as was high-grade pneumonia (20.8% vs. 15.3%; RR, 1.38; 95% CI 1.06-1.81; <i>P</i> = 0.02). No statistically significant differences were observed between the isatuximab and control groups for any-grade URTIs, high-grade URTIs, or VTE.</p><p><strong>Discussion: </strong>This meta-analysis highlights a significant increase in the incidence of pneumonia with the addition of isatuximab to standard myeloma regimens, underscoring the need for routine antibiotic prophylaxis, thromboprophylaxis, vigilant monitoring and early intervention to mitigate these risks.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002300"},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}