{"title":"Efficacy and Safety of Immune Checkpoint Inhibitors in Triple-negative Breast Cancer: A Study Based on 41 Cohorts Incorporating 6558 Participants.","authors":"Qing Wu, Chunlan Wu, Xianhe Xie","doi":"10.1097/CJI.0000000000000447","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000447","url":null,"abstract":"<p><p>The project was designed to investigate the efficacy and safety of immune checkpoint inhibitors (ICIs) in triple-negative breast cancer (TNBC). Electronic databases were screened to identify relevant trials. The primary endpoints were prognostic parameters and adverse events (AEs) through pooled rate, odds ratio, and hazard ratio (HR) with 95% CI. Totally, 6558 TNBC patients from 41 cohorts were included. The pooled pathologic complete response rate (odds ratio=2.03, 95% CI: 1.35-3.06, P =0.0007) and event-free survival (HR=0.84, 95% CI: 0.73-0.96, P =0.0100) of ICIs plus chemotherapy was higher than that of chemotherapy-alone in early-stage TNBC. For metastatic TNBC, compared with chemotherapy-alone, the addition of ICIs prolonged the progression-free survival (PFS) (HR=0.92, 95% CI: 0.88-0.96, P <0.0001); the improvement also existed in the following 3 subgroups: programmed cell death-ligand 1 positive, race of White and Asian, and patients without previous neoadjuvant or adjuvant chemotherapy; however, the benefit of the combined regimen was not observed in overall survival (OS) (HR=0.95; 95% CI: 0.89-1.03, P =0.2127). In addition, the pooled rates of OS, PFS, and objective response rate of ICIs plus chemotherapy were better than those of ICIs plus targeted therapy or ICIs-alone. In the safety analysis, compared with chemotherapy-alone, ICIs plus chemotherapy increased immune-related AEs and several serious AE. The regimen of ICIs plus chemotherapy is promising in both early-stage and metastatic TNBC, while the increased serious AE should not be neglected. Furthermore, the pooled rates of OS, PFS, and objective response rate of ICIs plus chemotherapy were better than those of ICIs plus targeted therapy or ICIs-alone.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":"46 2","pages":"29-42"},"PeriodicalIF":3.9,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10735611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of Antacid Use on Immune Checkpoint Inhibitors in Advanced Solid Cancer Patients: A Systematic Review and Meta-analysis.","authors":"Ruiyi Deng, Hua Zhang, Yuan Li, Yanyan Shi","doi":"10.1097/CJI.0000000000000442","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000442","url":null,"abstract":"<p><p>The influence of antacids use on immune checkpoint inhibitor (ICI) efficacy remains unclear. A systematic review and meta-analysis was performed to evaluate the effect of proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) on ICI efficacy in advanced solid cancer patients. A systematic literature search in PubMed, EMBASE, and Web of Science was performed to retrieve studies investigating the effect of antacid use on ICI efficacy. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and immune-related adverse events were measured using hazard ratios (HRs) or odds ratios (ORs). Thirty studies enrolling 16,147 advanced cancer patients receiving ICI treatment were included. The pooled analysis indicated that PPI use was associated with shorter OS (HR=1.40, 95% CI, 1.25-1.57) and PFS (HR=1.34, 95% CI, 1.19-1.52) in advanced cancer patients treated with ICIs. PPI use did not show effect on ORR or immune-related adverse event of advanced cancer patients receiving ICI treatment. OS, PFS, and ORR did not differ between H2RA users and non-H2RA users. In subgroup analyses, PPI use was associated with shorter OS and PFS in NSCLC and urothelial carcinoma patients and in patients treated with anti-programmed cell death 1 or anti-programmed cell death ligand 1 monotherapy. In addition, ICI efficacy was different in the antacid exposure time frame subgroups. In conclusion, PPI use has a negative effect on OS and PFS among advanced cancer patients receiving ICI treatment. PPIs should be cautiously administered among advanced cancer patients treated with ICI. The safety of H2RAs and the influence of H2RAs on ICI efficacy need further investigation.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":"46 2","pages":"43-55"},"PeriodicalIF":3.9,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9295242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francisco Zambrana, Carmen Barbancho, Miriam Huelves, Belén García de Santiago, Yolanda Martín, Marta Muñoz de Lengaria, Guillermo de Velasco
{"title":"Successful Pregnancy and Cancer Outcomes With Ipilimumab and Nivolumab for Metastatic Renal Cell Carcinoma: Case Report and Review of the Literature.","authors":"Francisco Zambrana, Carmen Barbancho, Miriam Huelves, Belén García de Santiago, Yolanda Martín, Marta Muñoz de Lengaria, Guillermo de Velasco","doi":"10.1097/CJI.0000000000000448","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000448","url":null,"abstract":"<p><p>Pregnancy and cancer share CTLA-4 and PD-1/PD-L1 as some of the immunomodulatory pathways that reshape the immune system from a destructive response to a state of tolerance to the fetus and the tumor, respectively. Ipilimumab (anti-CTLA-4 inhibitor) and nivolumab (anti-PD-1 inhibitor) are used in combination for the treatment of metastatic renal cell carcinoma, and their use could theoretically result in an immune response against the fetus. Furthermore, these immune checkpoint inhibitors are immunoglobulin G antibodies that transfer from the mother to the fetus and may cause a direct toxicity. We present the first report of a metastatic renal cell carcinoma patient in which ipilimumab and nivolumab were successfully used starting in her first trimester of pregnancy, with sufficient follow-up to show favorable outcomes for both the mother and the child. We describe our management of this challenging case and we review the available evidence, coming from Developmental and Reproductive Toxicology Studies and case reports of metastatic melanoma patients.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":"46 1","pages":"27-28"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10506685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of ImmunotherapyPub Date : 2023-01-01Epub Date: 2022-11-01DOI: 10.1097/CJI.0000000000000444
Cody C Gowan, Mee Y Bartee, Erica Flores, Bulent A Aksoy, Conor Templeton, Kati Baillie, Myroslawa Happe, Eric Bartee
{"title":"The Combination of TIM3-Based Checkpoint Blockade and Oncolytic Virotherapy Regresses Established Solid Tumors.","authors":"Cody C Gowan, Mee Y Bartee, Erica Flores, Bulent A Aksoy, Conor Templeton, Kati Baillie, Myroslawa Happe, Eric Bartee","doi":"10.1097/CJI.0000000000000444","DOIUrl":"10.1097/CJI.0000000000000444","url":null,"abstract":"<p><p>T-cell immunoglobulin and mucin domain 3 (TIM3) is emerging as a potential target for antibody-based checkpoint blockade. However, the efficacy of TIM3 blockade in combination with other treatment modalities, has not been extensively studied. In the current work we combined TIM3 blockade with myxoma virus-based oncolytic virotherapy (OV). Our results demonstrate that myxoma virus's ability to initiate an immense antitumor immune response complements the ability of TIM3 blockade to shift the tumor microenvironment to a more proinflammatory state. As a result, the combination of TIM3 blockade and OV is able to completely eradicate established disease, while neither monotherapy is effective. These data represent the first demonstration that OV can enhance the efficacy of TIM3 blockade and suggest that this treatment may need to be incorporated into more aggressive, combinatorial regimens in order to fulfill its potential as an immunotherapeutic.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":"46 1","pages":"1-4"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9783015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10190020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saber A Amin, Michael J Baine, Ibur Rahman, Chi Lin
{"title":"The Association of Immunotherapy With the Overall Survival of Inoperable Stage III Non-small Cell Lung Cancer Patients Who Do Not Receive Chemoradiation.","authors":"Saber A Amin, Michael J Baine, Ibur Rahman, Chi Lin","doi":"10.1097/CJI.0000000000000443","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000443","url":null,"abstract":"<p><p>Immunotherapy has been approved for stage III non-small cell lung cancer (NSCLC) as consolidation therapy after chemoradiation in patients whose disease does not progress after chemoradiation. However, many patients do not receive chemoradiation due to either the drugs' side effects or poor performance status. This study's objective is to investigate the association of immunotherapy combined with chemotherapy or Radiotherapy (RT) with the overall survival (OS) of stage III NSCLC patients who do not receive chemoradiation. Patients with stage III NSCLC who received either chemotherapy or RT with or without immunotherapy were identified from NCDB. The Cox proportional hazard regression analysis was implied to assess the effect of immunotherapy on survival after adjusting the model for age at diagnosis, race, sex, education, treatment facility type, insurance status, comorbidity score, histology year of diagnosis, and treatment types, such as chemotherapy and radiation therapy. The final analysis included 32,328 patients, among whom 3,205 (9.9%) received immunotherapy. In the multivariable analysis adjusted for all the factors previously mentioned, immunotherapy was associated with significantly improved OS (HR: 0.76, CI: 0.71-0.81) compared with no immunotherapy. Treatment with chemotherapy plus immunotherapy was significantly associated with improved OS (HR: 0.83, CI: 0.77-0.90) compared with chemotherapy without immunotherapy. Further, RT plus immunotherapy was associated with significantly improved OS (HR: 0.62, CI: 0.54-0.70) compared with RT alone. In this comprehensive analysis, the addition of immunotherapy to chemotherapy or radiotherapy was associated with improved OS compared with chemotherapy or radiation therapy without immunotherapy in stage III NSCLC patients.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":"46 1","pages":"14-21"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10136391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Justin C Boucher, Bin Yu, Gongbo Li, Bishwas Shrestha, David Sallman, Ana Marie Landin, Cheryl Cox, Kumar Karyampudi, Claudio Anasetti, Marco L Davila, Nelli Bejanyan
{"title":"Large Scale Ex Vivo Expansion of γδ T cells Using Artificial Antigen-presenting Cells.","authors":"Justin C Boucher, Bin Yu, Gongbo Li, Bishwas Shrestha, David Sallman, Ana Marie Landin, Cheryl Cox, Kumar Karyampudi, Claudio Anasetti, Marco L Davila, Nelli Bejanyan","doi":"10.1097/CJI.0000000000000445","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000445","url":null,"abstract":"<p><p>Higher γδ T cell counts in patients with malignancies are associated with better survival. However, γδ T cells are rare in the blood and functionally impaired in patients with malignancies. Promising results are reported on the treatment of various malignancies with in vivo expansion of autologous γδ T cells using zoledronic acid (zol) and interleukin-2 (IL-2). Here we demonstrated that zol and IL-2, in combination with a novel genetically engineered K-562 CD3scFv/CD137L/CD28scFv/IL15RA quadruplet artificial antigen-presenting cell (aAPC), efficiently expand allogeneic donor-derived γδ T cells using a Good Manufacturing Practice (GMP) compliant protocol sufficient to achieve cell doses for future clinical use. We achieved a 633-fold expansion of γδ T cells after day 10 of coculture with aAPC, which exhibited central (47%) and effector (43%) memory phenotypes. In addition, >90% of the expanded γδ T cells expressed NKG2D, although they have low cell surface expression of PD1 and LAG3 inhibitory checkpoint receptors. In vitro real-time cytotoxicity analysis showed that expanded γδ T cells were effective in killing target cells. Our results demonstrate that large-scale ex vivo expansion of donor-derived γδ T cells in a GMP-like setting can be achieved with the use of quadruplet aAPC and zol/IL-2 for clinical application.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":"46 1","pages":"5-13"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a3/dc/cji-46-05.PMC9722378.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10136402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of ImmunotherapyPub Date : 2023-01-01Epub Date: 2022-11-04DOI: 10.1097/CJI.0000000000000446
Sebastiano Buti, Umberto Basso, Diana Giannarelli, Ugo De Giorgi, Marco Maruzzo, Roberto Iacovelli, Luca Galli, Camillo Porta, Francesco Carrozza, Giuseppe Procopio, Giuseppe Fonarini, Giovanni Lo Re, Matteo Santoni, Roberto Sabbatini, Antonio Cusmai, Paolo Andrea Zucali, Carlo Aschele, Editta Baldini, Elena Zafarana, Adolfo Favaretto, Silvana Leo, Alketa Hamzaj, Rosanna Mirabelli, Franco Nole', Silvia Zai, Claudio Chini, Cristina Masini, Sonia Fatigoni, Andrea Rocchi, Emiliano Tamburini, Alessio Cortellini, Melissa Bersanelli
{"title":"Concomitant Drugs Prognostic Score in Patients With Metastatic Renal Cell Carcinoma Receiving Ipilimumab and Nivolumab in the Compassionate Use Program in Italy: Brief Communication.","authors":"Sebastiano Buti, Umberto Basso, Diana Giannarelli, Ugo De Giorgi, Marco Maruzzo, Roberto Iacovelli, Luca Galli, Camillo Porta, Francesco Carrozza, Giuseppe Procopio, Giuseppe Fonarini, Giovanni Lo Re, Matteo Santoni, Roberto Sabbatini, Antonio Cusmai, Paolo Andrea Zucali, Carlo Aschele, Editta Baldini, Elena Zafarana, Adolfo Favaretto, Silvana Leo, Alketa Hamzaj, Rosanna Mirabelli, Franco Nole', Silvia Zai, Claudio Chini, Cristina Masini, Sonia Fatigoni, Andrea Rocchi, Emiliano Tamburini, Alessio Cortellini, Melissa Bersanelli","doi":"10.1097/CJI.0000000000000446","DOIUrl":"10.1097/CJI.0000000000000446","url":null,"abstract":"<p><p>A concomitant drug-based score was developed by our group and externally validated for prognostic and predictive purposes in patients with advanced cancer treated with immune checkpoint inhibitors (ICIs). The model considers the use of three classes of drugs within a month before initiating ICI, assigning score 1 for each between proton pump inhibitor and antibiotic administration until a month before immunotherapy initiation and score 2 in case of corticosteroid intake. In the present analysis, the drug score was validated in a prospective population of 305 patients with metastatic renal cell carcinoma treated with ipilimumab plus nivolumab in the first-line setting. The value of the model in predicting overall survival and progression-free survival was statistically significant and clinically meaningful, with an overall survival rate at 12 months of 73% vs. 44% (P<0.0001), and median progression-free survival of 11.6 (95% CI: 9.1-14.1) months versus 4.8 (95% CI: 2.7-7.0) months (P=0.002), respectively, for patients belonging to the favorable group (score 0-1) versus the unfavorable (score 2-4). Further development will be represented by the gut microbiome analysis according to the drug-based model classification and to the outcome of patients to ICI therapy to demonstrate the link between drug exposure and immune sensitivity.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":"46 1","pages":"22-26"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f2/be/cji-46-22.PMC10561686.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10134763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lisa Loksø Dietz, Natasja Toft Furman, Trine Vilsbøll Larsen, Tina Fuglsang Daugaard, Emil Aagaard Thomsen, Johanne Lade Keller, Lars Aagaard, Boe Sandahl Sorensen, Anders Lade Nielsen
{"title":"An Extended PD-L2 Cytoplasmic Domain Results From Alternative Splicing in NSCLC Cells.","authors":"Lisa Loksø Dietz, Natasja Toft Furman, Trine Vilsbøll Larsen, Tina Fuglsang Daugaard, Emil Aagaard Thomsen, Johanne Lade Keller, Lars Aagaard, Boe Sandahl Sorensen, Anders Lade Nielsen","doi":"10.1097/CJI.0000000000000439","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000439","url":null,"abstract":"<p><p>Antibody-based immunotherapy targeting the interaction between programmed cell death 1 (PD-1) and its ligand PD-L1 has shown impressive clinical outcomes in various cancer types, including nonsmall cell lung cancer (NSCLC). However, regulatory mechanisms in this immune checkpoint pathway still needs clarification. PD-L2 is structurally homologous to PD-L1 and is a second PD-1 ligand. Alternative mRNA splicing from the CD274 and PDCD1LG2 genes holds the potential to generate PD-L1 and PD-L2 isoforms, respectively, with novel functionality in regulation of the PD-1 immune checkpoint pathway. Here, we describe alternative splicing in NSCLC cells potentially generating eight different PD-L2 isoforms from the PDCD1LG2 gene. Extension of exon 6 by four nucleotides is the most prominent alternative splicing event and results in PD-L2 isoform V with a cytoplasmic domain containing a 10 amino acid extension. On average 13% of the PDCD1LG2 transcripts in NSCLC cell lines and 22% of the transcripts in NSCLC tumor biopsies encode PD-L2 isoform V. PD-L2 isoform V localizes to the cell surface membrane but less efficiently than the canonical PD-L2 isoform I. The cytoplasmic domains of PD-1 ligands can affect immune checkpoint pathways by conferring membrane localization and protein stability and thereby represent alternative targets for immunotherapy. In addition, cytoplasmic domains are involved in intracellular signalling cascades in cancer cells. The presented observations of different cytoplasmic domains of PD-L2 will be important in the future delineation of the PD-1 immune checkpoint pathway.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":"45 9","pages":"379-388"},"PeriodicalIF":3.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10135840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Na Zhang, Jingbo Shao, Hong Li, Jiashi Zhu, Min Xia, Kai Chen, Hui Jiang
{"title":"Humanized CD19-directed CAR-T Cell Therapy in Pediatric Relapsed/Refractory Acute Lymphoblastic Leukemia With CNSL or Neurological Comorbidity.","authors":"Na Zhang, Jingbo Shao, Hong Li, Jiashi Zhu, Min Xia, Kai Chen, Hui Jiang","doi":"10.1097/CJI.0000000000000437","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000437","url":null,"abstract":"<p><p>Chimeric antigen receptor T cell (CAR-T) therapy has breakthrough potential for relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). However, because of the risk for neurotoxicity, trials usually exclude patients with central nervous system leukemia (CNSL) or active neurological comorbidities (NC). Here, we evaluated the efficacy and neurotoxicity of humanized CD19-directed CAR-T therapy for R/R ALL with CNSL or NC. Of 12 enrolled patients, 4 had CNSL with bone marrow (BM) or testicular recurrence, 3 had BM relapses with NC, and 5 had BM relapse without NC. Bridging chemotherapy was performed for high tumor burden before CAR-T therapy. Patients with CNSL or BM relapse with NC or without NC experienced 100% complete remission. Tumor burden reduction did not occur in 1 patient with NC, who developed grade 5 neurotoxicity before BM assessment, and one patient with CNSL developed leukoencephalopathy. Severe cytokine release syndrome and neurotoxicity developed in 0% with CNSL, 33.3% with BM relapse and NC, and 0% without NC. CAR-T cells expanded in the cerebrospinal fluid (CSF) of all patients with no difference among CNSL, BM with NC, or no NC (respective median percentages among lymphocyte: 33.7%, 48.2% and 34.5%, P =0.899; respective median concentrations: 0.82, 2.21, and 0.46/μL, P =0.719). Median CSF CAR-T cell duration was 5.5 (3-9) months with CNSL and 3 (2-3) months without CNSL ( P =0.031). CAR-T can be given safely and effectively to pediatric patients with R/R ALL with CNSL or NC who have near-normal neurological status. High tumor burden may confer increased risk for severe neurotoxicity.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":"45 9","pages":"396-406"},"PeriodicalIF":3.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7e/44/cji-45-396.PMC9528944.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10135837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mengni Guo, Jieying Liu, Ruoyu Miao, Zohaib Ahmed, James Yu, Jian Guan, Sarfraz Ahmad, Shuntai Zhou, Angela Grove, Manoucher Manoucheri, Mark A Socinski, Tarek Mekhail
{"title":"A Single Center Retrospective Study of the Impact of COVID-19 Infection on Immune-related Adverse Events in Cancer Patients Receiving Immune Checkpoint Inhibitors.","authors":"Mengni Guo, Jieying Liu, Ruoyu Miao, Zohaib Ahmed, James Yu, Jian Guan, Sarfraz Ahmad, Shuntai Zhou, Angela Grove, Manoucher Manoucheri, Mark A Socinski, Tarek Mekhail","doi":"10.1097/CJI.0000000000000440","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000440","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) can cause a variety of immune-related adverse events (irAEs). The coronavirus disease 2019 (COVID-19) is associated with increased amounts of pro-inflammatory cytokines, which may affect the outcome of irAEs. Data are limited regarding the impact of COVID-19 on irAEs in ICI-treated cancer patients. Hence, in this study, we retrospectively analyzed ICI-treated adult patients with malignant solid tumors at a single institution between August 2020 and August 2021. Patients who had the most recent ICI treatment over 1-month before or after the positive COVID-19 test were excluded from the study. For the COVID-19 positive group, only the irAEs that developed after COVID-19 infection were considered as events. A total of 579 patients were included in our study, with 46 (7.9%) in the COVID-19 positive group and 533 (92.1%) in the COVID-19 negative group. The baseline characteristics of patients in the 2 groups were similar. With a median follow-up of 331 days (range: 21-2226), we noticed a nonsignificant higher incidence of all-grade irAEs in the COVID-19 positive group (30.4% vs. 19.9%, P =0.18). The incidence of grade 3 and 4 irAEs was significantly higher in the COVID-19 positive group (10.9% vs. 3.2%, P =0.02). Multivariate analysis confirmed the association between COVID-19 infection and increased risk of severe irAE development (odds ratio: 1.08, 95% confidence interval: 1.02-1.14, P =0.01). Our study suggested that COVID-19 may pose a risk of severe irAEs in cancer patients receiving ICIs. Close monitoring and possibly delaying ICI administration could be considered when cancer patients are infected with COVID-19.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":"45 9","pages":"389-395"},"PeriodicalIF":3.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9528807/pdf/cji-45-389.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10189474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}