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British Journal of Haematology Mar 2023The prognosis of multiple myeloma (MM) has dramatically improved with the development of new drugs, and it has become important to determine the appropriate combinations... (Meta-Analysis)
Meta-Analysis Review
The prognosis of multiple myeloma (MM) has dramatically improved with the development of new drugs, and it has become important to determine the appropriate combinations of these novel agents. This study was a systematic review and network meta-analysis (NMA) of randomized trials in patients with relapsed and/or refractory (RR) MM. The PubMed, Cochrane, and Embase databases were searched for randomized trials from 1 January 2002 to 28 February 2022 of patients treated for MM. The primary end-point was progression-free survival (PFS), evaluated as a hazard ratio (HR) with a 95% confidence interval (95% CI) compared to dexamethasone (DEX). The p-score was used to rank treatments. Of a total of 1136 abstracts screened, 37 studies were selected, including 34 treatment options for RRMM. Daratumumab, lenalidomide and DEX was found to be the best treatment for RRMM, with the best HR compared to DEX (HR, 0.13; 95% CI, 0.08-0.20; p-score 0.9796). There was no evidence of significant heterogeneity (I , 41.3%; p = 0.146). The current NMA confirmed the excellent efficacy of three-drug regimens including anti-CD38 antibodies to treat RRMM and provides background data to evaluate the efficacy of chimeric antigen receptor T-cell treatments and bispecific T-cell engager therapies.
Topics: Humans; Multiple Myeloma; Network Meta-Analysis; Antineoplastic Combined Chemotherapy Protocols; Lenalidomide; Progression-Free Survival; Dexamethasone
PubMed: 36661264
DOI: 10.1111/bjh.18654 -
Journal of Hepatology Dec 2022HBV reactivation (HBVr) can be prevented by nucleos(t)ide analogues (NAs). We conducted a systematic review and meta-analysis on the risk of HBVr associated with new... (Meta-Analysis)
Meta-Analysis Review
HBV reactivation (HBVr) can be prevented by nucleos(t)ide analogues (NAs). We conducted a systematic review and meta-analysis on the risk of HBVr associated with new classes of immunosuppressive and immunomodulatory therapies and developed guidance on NA prophylaxis. An expert panel reviewed the data and categorised the risk of HBVr associated with each class of drugs into low (<1%), intermediate (1-10%), and high (>10%). Our search uncovered 59 studies, including 3,424 HBsAg+ and 5,799 HBsAg-/anti-HBc+ patients, which met our eligibility criteria. Based on medium-high quality evidence, immune checkpoint inhibitors, tyrosine kinase inhibitors, cytokine inhibitors, chimeric antigen receptor T-cell immunotherapies, and corticosteroids were associated with high HBVr risk in HBsAg+ patients; cytokine inhibitors, chimeric antigen receptor T-cell immunotherapies, and corticosteroids with intermediate risk in HBsAg-/anti-HBc+ patients; and anti-tumour necrosis factor agents and immune checkpoint inhibitors with low risk in HBsAg-/anti-HBc+ patients. Provisional recommendations are provided for drugs with low quality evidence. NA prophylaxis is recommended when using drugs associated with a high HBVr risk, while monitoring with on-demand NAs is recommended for low-risk drugs - either approach may be appropriate for intermediate-risk drugs. Consensus on definitions and methods of reporting HBVr, along with inclusion of HBsAg+, and HBsAg-/anti-HBc+ patients in clinical trials, will be key to gathering reliable data on the risk of HBVr associated with immunosuppressive or immunomodulatory therapies.
Topics: Humans; Hepatitis B virus; Hepatitis B Surface Antigens; Hepatitis B; Immunosuppressive Agents; Virus Activation; Expert Testimony; Immune Checkpoint Inhibitors; Receptors, Chimeric Antigen; Antiviral Agents; Hepatitis B Antibodies; Adjuvants, Immunologic; Cytokines
PubMed: 35850281
DOI: 10.1016/j.jhep.2022.07.003 -
Journal of Clinical Oncology : Official... Dec 2021To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events (irAEs) in patients treated with chimeric... (Meta-Analysis)
Meta-Analysis
PURPOSE
To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events (irAEs) in patients treated with chimeric antigen receptor (CAR) T-cell therapy.
METHODS
A multidisciplinary panel of medical oncology, neurology, hematology, emergency medicine, nursing, trialists, and advocacy experts was convened to develop the guideline. Guideline development involved a systematic literature review and an informal consensus process. The systematic review focused on evidence published from 2017 to 2021.
RESULTS
The systematic review identified 35 eligible publications. Because of the paucity of high-quality evidence, recommendations are based on expert consensus.
RECOMMENDATIONS
The multidisciplinary team issued recommendations to aid in the recognition, workup, evaluation, and management of the most common CAR T-cell-related toxicities, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, B-cell aplasia, cytopenias, and infections. Management of short-term toxicities associated with CAR T cells begins with supportive care for most patients, but may require pharmacologic interventions for those without adequate response. Management of patients with prolonged or severe CAR T-cell-associated cytokine release syndrome includes treatment with tocilizumab with or without a corticosteroid. On the basis of the potential for rapid decline, patients with moderate to severe immune effector cell-associated neurotoxicity syndrome should be managed with corticosteroids and supportive care.Additional information is available at www.asco.org/supportive-care-guidelines.
Topics: Cytokine Release Syndrome; Disease Management; Drug-Related Side Effects and Adverse Reactions; Humans; Immunotherapy, Adoptive; Neoplasms; Practice Guidelines as Topic; Prognosis
PubMed: 34724386
DOI: 10.1200/JCO.21.01992 -
European Journal of Nuclear Medicine... Mar 2021In recent years, the clinical availability of scanners for integrated positron emission tomography (PET) and magnetic resonance imaging (MRI) has enabled the practical... (Meta-Analysis)
Meta-Analysis Review
AIM
In recent years, the clinical availability of scanners for integrated positron emission tomography (PET) and magnetic resonance imaging (MRI) has enabled the practical potential of multimodal, combined metabolic-receptor, anatomical, and functional imaging to be explored. The present systematic review and meta-analysis summarize the diagnostic information provided by PET/MRI in patients with prostate cancer (PCa).
MATERIALS AND METHODS
A literature search was conducted in three different databases. The terms used were "choline" or "prostate-specific membrane antigen - PSMA" AND "prostate cancer" or "prostate" AND "PET/MRI" or "PET MRI" or "PET-MRI" or "positron emission tomography/magnetic resonance imaging." All relevant records identified were combined, and the full texts were retrieved. Reports were excluded if (1) they did not consider hybrid PET/MRI; or (2) the sample size was < 10 patients; or (3) the raw data were not enough to enable the completion of a 2 × 2 contingency table.
RESULTS
Fifty articles were eligible for systematic review, and 23 for meta-analysis. The pooled data concerned 2104 patients. Initial disease staging was the main indication for PET/MRI in 24 studies. Radiolabeled PSMA was the tracer most frequently used. In primary tumors, the pooled sensitivity for the patient-based analysis was 94.9%. At restaging, the pooled detection rate was 80.9% and was higher for radiolabeled PSMA than for choline (81.8% and 77.3%, respectively).
CONCLUSIONS
PET/MRI proved highly sensitive in detecting primary PCa, with a high detection rate for recurrent disease, particularly when radiolabeled PSMA was used.
Topics: Humans; Magnetic Resonance Imaging; Male; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prostatic Neoplasms; Radiopharmaceuticals; Tomography, X-Ray Computed
PubMed: 32901351
DOI: 10.1007/s00259-020-05025-0 -
JAMA Oncology Jul 2019Programmed cell death (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in cancer therapy. Understanding the treatment-related... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Programmed cell death (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in cancer therapy. Understanding the treatment-related adverse events of these drugs is critical for clinical practice.
OBJECTIVE
To evaluate the incidences of treatment-related adverse events of PD-1 and PD-L1 inhibitors and the differences between different drugs and cancer types.
DATA SOURCES
PubMed, Web of Science, Embase, and Scopus were searched from October 1, 2017, through December 15, 2018.
STUDY SELECTION
Published clinical trials on single-agent PD-1 and PD-L1 inhibitors with tabulated data on treatment-related adverse events were included.
DATA EXTRACTION AND SYNTHESIS
Trial name, phase, cancer type, PD-1 and PD-L1 inhibitor used, dose escalation, dosing schedule, number of patients, number of all adverse events, and criteria for adverse event reporting data were extracted from each included study, and bayesian multilevel regression models were applied for data analysis.
MAIN OUTCOMES AND MEASURES
Incidences of treatment-related adverse events and differences between different drugs and cancer types.
RESULTS
This systematic review and meta-analysis included 125 clinical trials involving 20 128 patients; 12 277 (66.0%) of 18 610 patients from 106 studies developed at least 1 adverse event of any grade (severity), and 2627 (14.0%) of 18 715 patients from 110 studies developed at least 1 adverse event of grade 3 or higher severity. The most common all-grade adverse events were fatigue (18.26%; 95% CI, 16.49%-20.11%), pruritus (10.61%; 95% CI, 9.46%-11.83%), and diarrhea (9.47%; 95% CI, 8.43%-10.58%). The most common grade 3 or higher adverse events were fatigue (0.89%; 95% CI, 0.69%-1.14%), anemia (0.78%; 95% CI, 0.59%-1.02%), and aspartate aminotransferase increase (0.75%; 95% CI, 0.56%-0.99%). Hypothyroidism (6.07%; 95% CI, 5.35%-6.85%) and hyperthyroidism (2.82%; 95% CI, 2.40%-3.29%) were the most frequent all-grade endocrine immune-related adverse events. Nivolumab was associated with higher mean incidences of all-grade adverse events compared with pembrolizumab (odds ratio [OR], 1.28; 95% CI, 0.97-1.79) and grade 3 or higher adverse events (OR, 1.30; 95% CI, 0.89-2.00). PD-1 inhibitors were associated with a higher mean incidence of grade 3 or higher adverse events compared with PD-L1 inhibitors (OR, 1.58; 95% CI, 1.00-2.54).
CONCLUSIONS AND RELEVANCE
Different PD-1 and PD-L1 inhibitors appear to have varying treatment-related adverse events; a comprehensive summary of the incidences of treatment-related adverse events in clinical trials provides an important guide for clinicians.
Topics: Antineoplastic Agents, Immunological; B7-H1 Antigen; Clinical Trials as Topic; Humans; Neoplasms; Programmed Cell Death 1 Receptor
PubMed: 31021376
DOI: 10.1001/jamaoncol.2019.0393 -
Transplantation and Cellular Therapy Jun 2022Chimeric antigen receptor (CAR) T cell therapy is a novel therapy for patients with relapsed or refractory hematologic malignancies. Most CAR T cell therapy recipients... (Review)
Review
Clinical Presentation, Risk Factors, and Outcomes of Immune Effector Cell-Associated Neurotoxicity Syndrome Following Chimeric Antigen Receptor T Cell Therapy: A Systematic Review.
Chimeric antigen receptor (CAR) T cell therapy is a novel therapy for patients with relapsed or refractory hematologic malignancies. Most CAR T cell therapy recipients will experience clinical features of the immune effector cell-associated neurotoxicity syndrome (ICANS), a potentially life-threatening condition. Here we describe the clinical, biological, and radiological findings associated with ICANS in adults with hematologic malignancies treated with CAR T cell therapy, as well as the acute and long-term outcomes of ICANS. A literature search of Ovid Medline, Embase, PubMed, Scopus, Web of Science Core Collection, Cochrane Library, and Google Scholar was conducted from each database's inception through February 1, 2022, using search terms reflecting CAR T cell therapy and ICANS. We included studies that enrolled adults (age ≥18 years) who received CAR T cell therapy as management for hematologic malignancies and reported the clinical presentation, predictors, and/or acute or long-term outcomes of ICANS. Two reviewers independently extracted data following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) reporting guidelines. Quality was assessed using the Joanna Briggs Institute critical appraisal tool for cohort studies. Of the 2928 studies screened, 23 observational studies (10 prospective, 11 retrospective, 1 mixed design, and 1 cross-sectional) with a total of 1666 participants met our eligibility criteria and were included in our review. The most common hematologic malignancies were diffuse large B cell lymphoma, acute lymphocytic leukemia, non-Hodgkin lymphoma, and chronic lymphocytic leukemia. ICANS onset was most often associated with the presence and severity of cytokine release syndrome, as well as with C-reactive protein and ferritin levels. Aphasia was the most common ICANS-related symptom reported, although the neurologic manifestations of ICANS were highly variable. Neuroimaging studies (magnetic resonance imaging or computed tomography) were often normal in cases of ICANS; however, electroencephalography often showed generalized background slowing, abnormal rhythmic, and periodic discharge patterns. The pooled mean (± SD) onset of ICANS was 6.4 ± 3.2 days, with a pooled mean duration of 8.3 ± 10.5 days. Two of the 23 studies (9%) reported 5 ICANS-related deaths among 233 participants. A subset of patients experienced persistent neurocognitive complaints at ≥1-year after CAR T cell therapy. The clinical presentation, onset, severity, long-term sequelae, and grading system of ICANS are variable. Future studies should consider using a consensus grading/reporting scale that would permit cross-trial comparisons of the safety profile of various CAR T cell products and enable the development of interventions to mitigate or manage these neurotoxicities. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. This systematic review was conducted according to a published protocol (PROSPERO CRD42020207864) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Synthesis without Meta-Analysis (SWiM) in systematic review reporting guidelines (Supplementary Table S1) [15,16].
Topics: Adult; Cell- and Tissue-Based Therapy; Cross-Sectional Studies; Hematologic Neoplasms; Humans; Immunotherapy, Adoptive; Neurotoxicity Syndromes; Prospective Studies; Receptors, Chimeric Antigen; Retrospective Studies; Risk Factors
PubMed: 35288347
DOI: 10.1016/j.jtct.2022.03.006 -
Journal of Hematology & Oncology Dec 2020B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T-cell therapy is an emerging treatment option for multiple myeloma. The aim of this systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T-cell therapy is an emerging treatment option for multiple myeloma. The aim of this systematic review and meta-analysis was to determine its safety and clinical activity and to identify factors influencing these outcomes.
METHODS
We performed a database search using the terms "BCMA," "CAR," and "multiple myeloma" for clinical studies published between 01/01/2015 and 01/01/2020. The methodology is further detailed in PROSPERO (CRD42020125332).
RESULTS
Twenty-three different CAR-T-cell products have been used so far in 640 patients. Cytokine release syndrome was observed in 80.3% (69.0-88.2); 10.5% (6.8-16.0) had neurotoxicity. A higher neurotoxicity rate was reported in studies that included more heavily pretreated patients: 19.1% (13.3-26.7; I = 45%) versus 2.8% (1.3-6.1; I = 0%) (p < 0.0001). The pooled overall response rate was 80.5% (73.5-85.9); complete responses (CR) were observed in 44.8% (35.3-54.6). A pooled CR rate of 71.9% (62.8-79.6; I = 0%) was noted in studies using alpaca/llama-based constructs, whereas it was only 18.0% (6.5-41.1; I = 67%) in studies that used retroviral vectors for CAR transduction. Median progression-free survival (PFS) was 12.2 (11.4-17.4) months, which compared favorably to the expected PFS of 1.9 (1.5-3.7) months (HR 0.14; p < 0.0001).
CONCLUSIONS
Although considerable toxicity was observed, BCMA-targeted CAR-T-cell therapy is highly efficacious even in advanced multiple myeloma. Subgroup analysis confirmed the anticipated inter-study heterogeneity and identified potential factors contributing to safety and efficacy. The results of this meta-analysis may assist the future design of CAR-T-cell studies and lead to optimized BCMA CAR-T-cell products.
Topics: B-Cell Maturation Antigen; Cytokine Release Syndrome; Humans; Immunotherapy, Adoptive; Multiple Myeloma; Neurotoxicity Syndromes; Progression-Free Survival; Receptors, Chimeric Antigen; Treatment Outcome
PubMed: 33272302
DOI: 10.1186/s13045-020-01001-1 -
Annals of Oncology : Official Journal... Aug 2019Cancers with a defective DNA mismatch repair (dMMR) system contain thousands of mutations most frequently located in monomorphic microsatellites and are thereby defined...
ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach.
BACKGROUND
Cancers with a defective DNA mismatch repair (dMMR) system contain thousands of mutations most frequently located in monomorphic microsatellites and are thereby defined as having microsatellite instability (MSI). Therefore, MSI is a marker of dMMR. MSI/dMMR can be identified using immunohistochemistry to detect loss of MMR proteins and/or molecular tests to show microsatellite alterations. Together with tumour mutational burden (TMB) and PD-1/PD-L1 expression, it plays a role as a predictive biomarker for immunotherapy.
METHODS
To define best practices to implement the detection of dMMR tumours in clinical practice, the ESMO Translational Research and Precision Medicine Working Group launched a collaborative project, based on a systematic review-approach, to generate consensus recommendations on the: (i) definitions related to the concept of MSI/dMMR; (ii) methods of MSI/dMMR testing and (iii) relationships between MSI, TMB and PD-1/PD-L1 expression.
RESULTS
The MSI-related definitions, for which a consensus frame-work was used to establish definitions, included: 'microsatellites', 'MSI', 'DNA mismatch repair' and 'features of MSI tumour'. This consensus also provides recommendations on MSI testing; immunohistochemistry for the mismatch repair proteins MLH1, MSH2, MSH6 and PMS2 represents the first action to assess MSI/dMMR (consensus with strong agreement); the second method of MSI/dMMR testing is represented by polymerase chain reaction (PCR)-based assessment of microsatellite alterations using five microsatellite markers including at least BAT-25 and BAT-26 (strong agreement). Next-generation sequencing, coupling MSI and TMB analysis, may represent a decisive tool for selecting patients for immunotherapy, for common or rare cancers not belonging to the spectrum of Lynch syndrome (very strong agreement). The relationships between MSI, TMB and PD-1/PD-L1 expression are complex, and differ according to tumour types.
CONCLUSIONS
This ESMO initiative is a response to the urgent questions raised by the growing success of immunotherapy and provides also important insights on the relationships between MSI, TMB and PD-1/PD-L1.
Topics: Antineoplastic Agents, Immunological; B7-H1 Antigen; Biomarkers, Tumor; DNA Mismatch Repair; DNA Mutational Analysis; European Union; Genetic Testing; High-Throughput Nucleotide Sequencing; Humans; Immunohistochemistry; Medical Oncology; Microsatellite Instability; Mutation; Neoplasms; Patient Selection; Practice Guidelines as Topic; Programmed Cell Death 1 Receptor; Societies, Medical
PubMed: 31056702
DOI: 10.1093/annonc/mdz116 -
The Cochrane Database of Systematic... Sep 2021Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer of the lymphatic system. About 30% to 40% of people with DLBCL experience relapse and 10% are refractory to... (Review)
Review
BACKGROUND
Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer of the lymphatic system. About 30% to 40% of people with DLBCL experience relapse and 10% are refractory to first-line treatment usually consisting of R-CHOP chemotherapy. Of those eligible for second-line treatment, commonly consisting of salvage chemotherapy followed by autologous stem-cell transplantation (ASCT), around 50% experience relapse. With a median overall survival of less than six to 12 months, the prognosis of individuals who relapse or are refractory (r/r) to advanced lines of treatment or of those who are ineligible for ASCT, is very poor. With the introduction of chimeric antigen receptor (CAR) T-cell therapy, a novel treatment option for these people is available.
OBJECTIVES
To assess the benefits and harms of chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory (r/r) DLBCL.
SEARCH METHODS
An experienced information specialist performed a systematic database search for relevant articles on CENTRAL, MEDLINE and Embase until September 11th, 2020. We also searched trial registries and reference lists of identified studies up to this date. All search results were screened by two authors independently and a third author was involved in case of discrepancies.
SELECTION CRITERIA
We included prospectively planned trials evaluating CAR T-cell therapy for people with r/r DLBCL. We had planned to include randomised controlled trials (RCTs) and we flexibly adapted eligibility criteria to the most reliable study designs available. We excluded studies involving fewer than 10 participants with r/r DLBCL and studies with a proportion of participants with r/r DLBCL below 70%, unless data were reported separately for this subgroup.
DATA COLLECTION AND ANALYSIS
Two review authors extracted data and performed risk of bias ratings independently. A third author was involved in case of disagreements. As our search did not yield any completed RCTs, prospective controlled non-randomised studies of interventions (NRSIs) or prospective observational studies with a control group, we did not meta-analyse data and reported all results narratively. We adopted the GRADE approach to assess the certainty of the evidence for prioritised outcomes.
MAIN RESULTS
We identified 13 eligible uncontrolled studies evaluating a single or multiple arms of CAR T-cell therapies. We also identified 38 ongoing studies, including three RCTs. Ten studies are awaiting classification due to completion with no retrievable results data or insufficient data to justify inclusion. The mean number of participants enrolled, treated with CAR T-cell therapy and evaluated in the included studies were 79 (range 12 to 344; data unavailable for two studies), 61 (range 12 to 294; data unavailable for one study) and 52 (range 11 to 256), respectively. Most studies included people with r/r DLBCL among people with other haematological B-cell malignancies. Participants had received at least a median of three prior treatment lines (data unavailable for four studies), 5% to 50% had undergone ASCT (data unavailable for five studies) and, except for two studies, 3% to 18% had undergone allogenic stem-cell transplantation (data unavailable for eight studies). The overall risk of bias was high for all studies, in particular, due to incomplete follow-up and the absence of blinding. None of the included studies had a control group so that no adequate comparative effect measures could be calculated. The duration of follow-up varied substantially between studies, in particular, for harms. Our certainty in the evidence is very low for all outcomes. Overall survival was reported by eight studies (567 participants). Four studies reported survival rates at 12 months which ranged between 48% and 59%, and one study reported an overall survival rate of 50.5% at 24 months. The evidence is very uncertain about the effect of CAR T-cell therapy on overall survival. Two studies including 294 participants at baseline and 59 participants at the longest follow-up (12 months or 18 months) described improvements of quality of life measured with the EuroQol 5-Dimension 5-Level visual analogue scale (EQ-5D-5L VAS) or Function Assessment of Cancer Therapy-Lymphoma (FACT-Lym). The evidence is very uncertain about the effect of CAR T-cell therapy on quality of life. None of the studies reported treatment-related mortality. Five studies (550 participants) reported the occurrence of adverse events among participants, ranging between 99% and 100% for any grade adverse events and 68% to 98% for adverse events grade ≥ 3. In three studies (253 participants), 56% to 68% of participants experienced serious adverse events, while in one study (28 participants), no serious adverse events occurred. CAR T-cell therapy may increase the risk of adverse events and serious adverse events but the evidence is very uncertain about the exact risk. The occurrence of cytokine release syndrome (CRS) was reported in 11 studies (675 participants) under use of various grading criteria. Five studies reported between 42% and 100% of participants experiencing CRS according to criteria described in Lee 2014. CAR T-cell therapy may increase the risk of CRS but the evidence is very uncertain about the exact risk. Nine studies (575 participants) reported results on progression-free survival, disease-free survival or relapse-free survival. Twelve-month progression-free survival rates were reported by four studies and ranged between 44% and 75%. In one study, relapse-free survival remained at a rate of 64% at both 12 and 18 months. The evidence is very uncertain about the effect of CAR T-cell therapy on progression-free survival. Thirteen studies (620 participants) provided data on complete response rates. At six months, three studies reported complete response rates between 40% and 45%. The evidence is very uncertain about the effect of CAR T-cell therapy on complete response rates.
AUTHORS' CONCLUSIONS
The available evidence on the benefits and harms of CAR T-cell therapy for people with r/r DLBCL is limited, mainly because of the absence of comparative clinical trials. The results we present should be regarded in light of this limitation and conclusions should be drawn very carefully. Due to the uncertainty in the current evidence, a large number of ongoing investigations and a risk of substantial and potentially life-threatening complications requiring supplementary treatment, it is critical to continue evaluating the evidence on this new therapy.
Topics: Cell- and Tissue-Based Therapy; Humans; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse; Neoplasm Recurrence, Local; Observational Studies as Topic; Receptors, Chimeric Antigen
PubMed: 34515338
DOI: 10.1002/14651858.CD013365.pub2 -
International Journal of Molecular... Sep 2022Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of... (Review)
Review
Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of advanced malignancies, like melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and Hodgkin lymphoma. ICIs act upon T lymphocytes and antigen-presenting cells, targeting programmed cell death protein 1 (PD1), programmed cell death protein ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), breaking the immune tolerance of the T cells against malignant cells and enhancing the body's own immune response. A variety of cardiac-adverse effects are associated with ICI-based treatment, including pericarditis, arrhythmias, cardiomyopathy, and acute coronary syndrome, with myocarditis being the most studied due to its often-unexpected onset and severity. Overall, Myocarditis is rare but presents an immune-related adverse event (irAE) that has a high fatality rate. Considering the rising number of oncological patients treated with ICIs and the severity of their potential adverse effects, a good understanding and continuous investigation of cardiac irAEs is of the utmost importance. This systematic review aimed to revise recent publications (between 2016-2022) on ICI-induced cardiac toxicities and highlight the therapeutical approach and evolution in the selected cases.
Topics: Antineoplastic Agents, Immunological; Apoptosis Regulatory Proteins; B7-H1 Antigen; CTLA-4 Antigen; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Cardiotoxicity; Drug-Related Side Effects and Adverse Reactions; Humans; Immune Checkpoint Inhibitors; Ligands; Liver Neoplasms; Lung Neoplasms; Myocarditis; Programmed Cell Death 1 Receptor
PubMed: 36142866
DOI: 10.3390/ijms231810948