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Clinical Lymphoma, Myeloma & Leukemia Jan 2023Relapsed/refractory central nervous system (CNS) lymphoma, whether primary or secondary, is associated with poor prognosis with currently available treatment modalities,... (Review)
Review
Relapsed/refractory central nervous system (CNS) lymphoma, whether primary or secondary, is associated with poor prognosis with currently available treatment modalities, including high-dose chemotherapy-autologous stem cell transplantation. The pivotal ZUMA-1 and JULIET trials that led to FDA approval of Axicabtagene ciloleucel and Tisagenlecleucel for relapsed refractory large cell lymphoma excluded patients with CNS involvement due to concerns of increased toxicity. However, TRANSCEND study for Lisocabtagene maraleucel in relapsed refractory large cell lymphoma allowed patients with CNS involvement and reported manageable CNS toxicities in these patients. In the real-world experience, chimeric antigen receptor T-cell (CAR T) therapy has been deemed safe and effective for these patients with poor prognosis. In this systematic review, we analyzed available literature to evaluate the role of CAR T-cell therapy in both primary and secondary CNS lymphoma using Embase, Cochrane, and PubMed databases. A total of 14 studies, including 8 retrospective analyses and 6 prospective studies/clinical trials, were included in the qualitative synthesis to study the safety and efficacy of CAR T. Based on our analysis, CAR T-cell therapy appears to be associated with reasonable efficacy and a manageable safety for primary and secondary CNS lymphoma.
Topics: Humans; Receptors, Chimeric Antigen; Immunotherapy, Adoptive; T-Lymphocytes; Retrospective Studies; Hematopoietic Stem Cell Transplantation; Prospective Studies; Transplantation, Autologous; Receptors, Antigen, T-Cell; Antigens, CD19; Lymphoma; Central Nervous System Neoplasms; Lymphoma, Non-Hodgkin; Neoplasms, Second Primary; Central Nervous System; Lymphoma, Large B-Cell, Diffuse
PubMed: 36328891
DOI: 10.1016/j.clml.2022.09.008 -
Expert Review of Anti-infective Therapy Nov 2022Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment option for relapsed or refractory B-cell malignancies and multiple myeloma.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment option for relapsed or refractory B-cell malignancies and multiple myeloma. Underlying and treatment-related variables may contribute to the development of infectious complications.
RESEARCH DESIGN AND METHODS
We conducted a systematic review and meta-analysis on the incidence of overall and severe (grade ≥3) infection in patients with hematological malignancies receiving CAR T-cells. Secondary outcomes included the specific rates of bacterial, viral and invasive fungal infection (IFI), and infection-related mortality. PubMed, Embase and Web of Science databases were searched from inception to 27 May 2022. Sensitivity analysis were performed according to the type of malignancy and study design (randomized clinical trials [RCTs] or observational studies).
RESULTS
Forty-five studies (34 RCTs) comprising 3,591 patients were included. The pooled incidence rates of overall and severe infection were 33.8% (I = 96.31%) and 16.2% (I = 74.41%). The respiratory tract was the most common site of infection. Most events were bacterial or viral, whereas the occurrence of IFI was rare. The pooled attributable mortality was 1.8% (I = 43.44%).
CONCLUSIONS
Infection is a frequent adverse event in patients receiving CAR T-cell therapy. Further research should address specific risk factors in this population.
Topics: Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Antigens, CD19; Hematologic Neoplasms; Neoplasms
PubMed: 36148506
DOI: 10.1080/14787210.2022.2128762 -
International Journal of Biological... Oct 2022Antibodies play a crucial role in the defense mechanism countering pathogens or foreign antigens in eukaryotes. Its potential as an analytical and diagnostic tool has... (Review)
Review
Antibodies play a crucial role in the defense mechanism countering pathogens or foreign antigens in eukaryotes. Its potential as an analytical and diagnostic tool has been exploited for over a century. It forms immunocomplexes with a specific antigen, which is the basis of immunoassays and aids in developing potent biosensors. Antibody-based sensors allow for the quick and accurate detection of various analytes. Though classical antibodies have prolonged been used as bioreceptors in biosensors fabrication due to their increased fragility, they have been engineered into more stable fragments with increased exposure of their antigen-binding sites in the recent era. In biosensing, the formats constructed by antibody engineering can enhance the signal since the resistance offered by a conventional antibody is much more than these fragments. Hence, signal amplification can be observed when antibody fragments are utilized as bioreceptors instead of full-length antibodies. We present the first systematic review on engineered antibodies as bioreceptors with the description of their engineering methods. The detection of various target analytes, including small molecules, macromolecules, and cells using antibody-based biosensors, has been discussed. A comparison of the classical polyclonal, monoclonal, and engineered antibodies as bioreceptors to construct highly accurate, sensitive, and specific sensors is also discussed.
Topics: Antibodies; Antigens; Bioengineering; Biosensing Techniques
PubMed: 35870626
DOI: 10.1016/j.ijbiomac.2022.07.109 -
Oral Oncology Oct 2023HNSCC is one of the most common types of cancer worldwide and immune checkpoint inhibitor has shown favorable therapeutic effect in R/M HNSC. However, the application of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
HNSCC is one of the most common types of cancer worldwide and immune checkpoint inhibitor has shown favorable therapeutic effect in R/M HNSC. However, the application of immunotherapy in untreated HNSCC still needs to be discovered since most R/M HNSCC patients have been treated before and their drug susceptibility and immune tumor microenvironment have changed. This meta-analysis tries to compare immunotherapy and immunochemotherapy in untreated HNSCC and give a reference for clinic application.
METHODS
Electronic databases, including PubMed, Embase, and Web of Science, were systematically searched from inception through August 31, 2022. The primary outcomes were efficacy, evaluated by objective response rate, 1-year OS and 1-year PFS, and safety, evaluated by grade 3-4 adverse reaction rate.
RESULTS
A total of 1092 patients from twenty-four studies were included, 282 (25.8%) of which had ORR reported. The average ORR was 37% (95%CI = 26%-49%). Immunochemotherapy could have higher ORR than immunotherapy patients (ORR: 61% vs 22%), and favorable 1-year overall survival from PD-L1 inhibitor (OS = 84%, 95%CI 76%-93%). Radiotherapy after neoadjuvant immunotherapy was equal with the other treatments like chemotherapy and surgery (84% vs 88%, subgroup df p = 0.7). There was no apparent difference between immunotherapy and immunochemotherapy (32% vs 42%, subgroup df p = 0.60).
CONCLUSION
HNSCC patients could benefit more from neoadjuvant immunochemotherapy.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Neoadjuvant Therapy; Immunotherapy; Head and Neck Neoplasms; B7-H1 Antigen; Lung Neoplasms; Tumor Microenvironment
PubMed: 37478574
DOI: 10.1016/j.oraloncology.2023.106479 -
JAMA Network Open Jul 2021Hundreds of chimeric antigen receptor (CAR) therapies are under investigation for hematologic malignant cancers and solid malignant tumors. As the field of modern CAR...
IMPORTANCE
Hundreds of chimeric antigen receptor (CAR) therapies are under investigation for hematologic malignant cancers and solid malignant tumors. As the field of modern CAR therapy enters its second decade, clinical trials that demonstrate the efficacy of CAR therapies using randomized clinical trials (RCTs) and/or investigate methods to optimize patient outcomes with commercially available CAR therapies are increasingly important.
OBJECTIVE
To analyze the landscape of registered CAR-related trials with dual focuses on trial methods and intent.
EVIDENCE REVIEW
This systematic review identified 1304 ongoing or upcoming CAR-related trials registered at ClinicalTrials.gov as of December 22, 2020, and excluded 513 trials that did not pertain to cell-based therapy. Both CAR-related and trial-related variables, including target antigens and countries of origin, were recorded. Trials were categorized as non-RCTs that compared CAR with non-CAR therapies or RCTs in which every arm received CAR therapy. Trial intent was separately categorized as demonstrating the efficacy of a CAR therapy, optimizing patient outcomes with established CAR therapies using adjunctive non-CAR modalities, or miscellaneous.
FINDINGS
Of 778 relevant trials, 587 (75%) involved blood cancers, whereas 182 (23%) involved solid tumor cancers; the remaining 9 (1%) involved nonmalignant diseases. A total of 433 trials (56%) were from China and 288 from the US (37%). Ten RCTs (1%) compared CAR therapies with non-CAR therapies, including phase 3 RCTs for 4 of 5 CAR therapies (80%) that are currently commercially available. Twenty-eight studies (4%) sought to optimize outcomes with established CAR therapies using non-CAR drugs or radiotherapy, whereas 3 studies (0.4%) sought to optimize supportive care during CAR therapy.
CONCLUSIONS AND RELEVANCE
This systematic review found that randomized and optimization-focused trials are comparatively rare within the landscape of ongoing and upcoming CAR-related trials. As the field of modern CAR therapy enters its second decade, additional studies of these characteristics are necessary to strengthen the evidence base for CAR therapy and improve patient outcomes.
Topics: Humans; Immunotherapy, Adoptive; Research
PubMed: 34236412
DOI: 10.1001/jamanetworkopen.2021.15668 -
Expert Review of Pharmacoeconomics &... 2023The new class of chimeric antigen receptor T-cell has emboldened health-care professionals and patients for a more effective treatment of hematological malignancies,... (Review)
Review
INTRODUCTION
The new class of chimeric antigen receptor T-cell has emboldened health-care professionals and patients for a more effective treatment of hematological malignancies, indicatively lymphoma, acute lymphoblastic leukemia, and myeloma. Nevertheless, their burgeoning procurement costs comprise a litmus stress for health systems across the globe. In this context, this systematic review aims to update the current body of evidence assessing CAR-T economic evaluations and elucidate their financial efficiency.
AREAS COVERED
A systematic review of the economic evaluations of tisagenlecleucel, axicabtagene ciloleucel, idecabtagene vicleucel, lisocabtagene maraleucel, ciltacabtagene autoleucel and brexucabtagene autoleucel was performed.
EXPERT OPINION
The updated results corroborated the previously reported favorable cost-effectiveness ratio of CAR-T. They also pointed out differences among CAR-T agents. However, their budget impact emerges as a significant barrier in the reimbursement process. Any proposed Managed Entry Agreement must integrate the ingrained uncertainty of long-term efficacy and precede reimbursement decisions.
Topics: Humans; Cost-Benefit Analysis; Receptors, Chimeric Antigen; Immunotherapy, Adoptive; Budgets; Cell- and Tissue-Based Therapy
PubMed: 37288738
DOI: 10.1080/14737167.2023.2214731 -
International Journal of Molecular... May 2024Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell)... (Meta-Analysis)
Meta-Analysis Review
An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis.
Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell) therapy has emerged as a novel treatment, with the potential to improve the survival and quality of life of patients with relapsed/refractory multiple myeloma (rrMM). In this systematic review and meta-analysis, conducted in accordance with PRISMA guidelines, we aim to provide a concise overview of the latest developments in CAR-T therapy, assess their potential implications for clinical practice, and evaluate their efficacy and safety outcomes based on the most up-to-date evidence. A literature search conducted from 1 January 2019 to 12 July 2023 on Medline/PubMed, Scopus, and Web of Science identified 2273 articles, of which 29 fulfilled the specified criteria for inclusion. Our results offer robust evidence supporting CAR-T cell therapy's efficacy in rrMM patients, with an encouraging 83.21% overall response rate (ORR). A generally safe profile was observed, with grade ≥ 3 cytokine release syndrome (CRS) at 7.12% and grade ≥ 3 neurotoxicity at 1.37%. A subgroup analysis revealed a significantly increased ORR in patients with fewer antimyeloma regimens, while grade ≥ 3 CRS was more common in those with a higher proportion of high-risk cytogenetics and prior exposure to BCMA therapy.
Topics: Multiple Myeloma; Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Treatment Outcome; Quality of Life; Neoplasm Recurrence, Local; Cytokine Release Syndrome
PubMed: 38732213
DOI: 10.3390/ijms25094996 -
Frontiers in Immunology 2023The combination of nanoparticle albumin-bound paclitaxel (nab-PTX)/paclitaxel (PTX) with immune checkpoint inhibitors (ICIs) has demonstrated significant efficacy in... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The combination of nanoparticle albumin-bound paclitaxel (nab-PTX)/paclitaxel (PTX) with immune checkpoint inhibitors (ICIs) has demonstrated significant efficacy in cancer patients. However, the safety of these combination regimens remains conflicting in former researches. Therefore, in order to address this issue, we performed a systematic review and network meta-analysis (NMA) to evaluate and compare the safety profile.
METHODS
We performed a systematic review by searching randomized controlled trials (RCTs) from PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and Web of Science up to August 15, 2022. The primary outcomes were all-grade (grade 1-5) and high-grade (grade 3-5) immune-related adverse events (irAEs). Secondary outcomes were all-grade (grade 1-5) and high-grade (grade 3-5) irAEs of subgroups of ICIs.
RESULTS
There were 22 RCTs included in the NMA, involving a total of 15 963 patients diagnosed with any type of cancer. ICIs+nab-PTX was associated with a noticeably decreased risk of grade 3-5 pneumonitis (odds ratio [OR]=0.28, 95% credible interval [CrI]: 0.09,0.90) compared to ICI monotherapy; ICIs+PTX showed a lower risk of grade 1-5 hyperthyroidism (OR=0.46, 95% CrI: 0.22-0.96) and grade 1-5 hypothyroidism (OR=0.49, 95% CrI: 0.26-0.93) than ICIs. Compared with PD-1, PD-1+PTX was associated with a statistically significantly lower risk of grade 1-5 pneumonitis (OR=0.32, 95% CrI: 0.11-0.92). PD-L1 resulted in a noticeably lower risk of grade 1-5 hypothyroidism (OR=0.34, 95% CrI: 0.12-1.00) than PD-L1+PTX. Nearly all treatment regimens containing ICIs demonstrated significantly higher risks of irAEs compared to the standard chemotherapy groups.
CONCLUSION
Nab-PTX/PTX+ICIs demonstrated an approach leading to decreased risk of irAEs compared with ICI monotherapy. This finding supports that ICIs+nab-PTX/PTX may be a safer treatment strategy. Moreover, we also found that the combination regimens containing ICIs had a higher risk of irAEs than standard chemotherapy. Additionally, ICIs+nab-PTX demonstrated a decreased risk of irAEs compared to ICIs+PTX. PD-1 inhibitors were associated with a higher risk of irAEs than PD-L1 inhibitors.
Topics: Humans; Immune Checkpoint Inhibitors; B7-H1 Antigen; Antineoplastic Agents, Immunological; Programmed Cell Death 1 Receptor; Network Meta-Analysis; Neoplasms; Paclitaxel; Hypothyroidism; Pneumonia
PubMed: 37520574
DOI: 10.3389/fimmu.2023.1175809 -
Vaccines May 2021The current study systematically reviewed, summarized and meta-analyzed the clinical features of the vaccines in clinical trials to provide a better estimate of their... (Review)
Review
The current study systematically reviewed, summarized and meta-analyzed the clinical features of the vaccines in clinical trials to provide a better estimate of their efficacy, side effects and immunogenicity. All relevant publications were systematically searched and collected from major databases up to 12 March 2021. A total of 25 RCTs (123 datasets), 58,889 cases that received the COVID-19 vaccine and 46,638 controls who received placebo were included in the meta-analysis. In total, mRNA-based and adenovirus-vectored COVID-19 vaccines had 94.6% (95% CI 0.936-0.954) and 80.2% (95% CI 0.56-0.93) efficacy in phase II/III RCTs, respectively. Efficacy of the adenovirus-vectored vaccine after the first (97.6%; 95% CI 0.939-0.997) and second (98.2%; 95% CI 0.980-0.984) doses was the highest against receptor-binding domain (RBD) antigen after 3 weeks of injections. The mRNA-based vaccines had the highest level of side effects reported except for diarrhea and arthralgia. Aluminum-adjuvanted vaccines had the lowest systemic and local side effects between vaccines' adjuvant or without adjuvant, except for injection site redness. The adenovirus-vectored and mRNA-based vaccines for COVID-19 showed the highest efficacy after first and second doses, respectively. The mRNA-based vaccines had higher side effects. Remarkably few experienced extreme adverse effects and all stimulated robust immune responses.
PubMed: 34066475
DOI: 10.3390/vaccines9050467 -
Cancers Dec 2019Despite advances in the treatment of many pediatric solid tumors, children with aggressive and high-risk disease continue to have a dismal prognosis. For those... (Review)
Review
Despite advances in the treatment of many pediatric solid tumors, children with aggressive and high-risk disease continue to have a dismal prognosis. For those presenting with metastatic or recurrent disease, multiple rounds of intensified chemotherapy and radiation are the typical course of action, but more often than not, this fails to control the progression of the disease. Thus, new therapeutics are desperately needed to improve the outcomes for these children. Recent advances in our understanding of both the immune system's biology and its interaction with tumors have led to the development of novel immunotherapeutics as alternative treatment options for these aggressive malignancies. Immunotherapeutic approaches have shown promising results for pediatric solid tumors in early clinical trials, but challenges remain concerning safety and anti-tumor efficacy. In this review, we aim to discuss and summarize the main classes of immunotherapeutics used to treat pediatric solid tumors.
PubMed: 31847387
DOI: 10.3390/cancers11122022