Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 48
Filter
1.
Br J Nurs ; 31(8): 414-420, 2022 Apr 21.
Article in English | MEDLINE | ID: covidwho-1791705

ABSTRACT

This article discusses the implementation and development of a centralised immuno-oncology service. As the indications and licensing of oncological immune checkpoint inhibitors (ICIs) expanded rapidly, they brought with them increasing challenges. The article evaluates the impact of an immuno-oncology service, focusing on the following areas: admission rates due to immune-related adverse events (irAEs), number of bed days occupied due to immunotherapy toxicity and the incidence of Grade 3 and 4 (severe and life-threatening) irAEs. The article will also give an overview of patients requiring acute and subsequent management of toxicity as a percentage of the overall patients commenced on immunotherapy. The ultimate aim of the article is to highlight the importance of toxicity management and the overall benefits of a immuno-oncology service. The article will also discuss the impact of COVID-19 on the immuno-oncology service, highlighting the ways in which the team has adapted to the current environment to ensure high standards of patient care have been maintained.


Subject(s)
COVID-19 , Neoplasms, Second Primary , Neoplasms , Humans , Immunotherapy/adverse effects , Medical Oncology , Neoplasms/etiology , Neoplasms/therapy , Neoplasms, Second Primary/etiology , United Kingdom
2.
Thorax ; 77(3): 304-311, 2022 03.
Article in English | MEDLINE | ID: covidwho-1551065

ABSTRACT

Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment. However, immune-related adverse events (irAEs) are a common side effect which can mimic infection. Additionally, treatment of irAEs with corticosteroids and other immunosuppressant agents can lead to opportunistic infection, which we have classed as immunotherapy infections due to immunosuppression. However, emerging reports demonstrate that some infections can be precipitated by ICIs in the absence of immunosuppressive treatment, in contrast to the majority of reported cases. These infections are characterised by a dysregulated inflammatory immune response, and so we propose they are described as immunotherapy infections due to dysregulated immunity. This review summarises the rapidly emerging evidence of these phenomena and proposes a new framework for considering infection in the context of cancer immunotherapy.


Subject(s)
Neoplasms , Opportunistic Infections , Humans , Immune Checkpoint Inhibitors , Immunosuppressive Agents/adverse effects , Immunotherapy/adverse effects , Neoplasms/drug therapy , Opportunistic Infections/chemically induced
3.
Br J Cancer ; 126(1): 1-3, 2022 01.
Article in English | MEDLINE | ID: covidwho-1526066

ABSTRACT

The combination of COVID-19 vaccination with immunotherapy by checkpoint inhibitors in cancer patients could intensify immunological stimulation with potential reciprocal benefits. Here, we examine more closely the possible adverse events that can arise in each treatment modality. Our conclusion is that caution should be exercised when combining both treatments.


Subject(s)
/adverse effects , COVID-19/prevention & control , Immune Checkpoint Inhibitors/adverse effects , Immunotherapy/adverse effects , Neoplasms/therapy , /administration & dosage , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Combined Modality Therapy/adverse effects , Cytokine Release Syndrome/etiology , Drug Interactions , Humans , Immune Checkpoint Inhibitors/administration & dosage , Immunotherapy/methods , Neoplasms/immunology
4.
Mucosal Immunol ; 15(2): 198-210, 2022 02.
Article in English | MEDLINE | ID: covidwho-1493071

ABSTRACT

As the COVID-19 pandemic is still ongoing, and considering the lack of efficacy of antiviral strategies to this date, and the reactive hyperinflammation leading to tissue lesions and pneumonia, effective treatments targeting the dysregulated immune response are more than ever required. Immunomodulatory and immunosuppressive drugs have been repurposed in severe COVID-19 with contrasting results. The heterogeneity in the timing of treatments administrations could be accountable for these discrepancies. Indeed, many studies included patients at different timepoints of infection, potentially hiding the beneficial effects of a time-adapted intervention. We aim to review the available data on the kinetics of the immune response in beta-coronaviruses infections, from animal models and longitudinal human studies, and propose a four-step model of severe COVID-19 timeline. Then, we discuss the results of the clinical trials of immune interventions with regards to the timing of administration, and finally suggest a time frame in order to delineate the best timepoint for each treatment.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/therapy , Immunosuppressive Agents/administration & dosage , Immunotherapy , SARS-CoV-2/drug effects , Animals , Antiviral Agents/adverse effects , COVID-19/diagnosis , COVID-19/immunology , COVID-19/virology , Drug Administration Schedule , Host-Pathogen Interactions , Humans , Immunosuppressive Agents/adverse effects , Immunotherapy/adverse effects , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Time Factors , Treatment Outcome
5.
Front Immunol ; 12: 740249, 2021.
Article in English | MEDLINE | ID: covidwho-1448730

ABSTRACT

Objective: To assess in rheumatoid arthritis (RA) patients, treated with different immunosuppressive therapies, the induction of SARS-CoV-2-specific immune response after vaccination in terms of anti-region-binding-domain (RBD)-antibody- and T-cell-specific responses against spike, and the vaccine safety in terms of clinical impact on disease activity. Methods: Health care workers (HCWs) and RA patients, having completed the BNT162b2-mRNA vaccination in the last 2 weeks, were enrolled. Serological response was evaluated by quantifying anti-RBD antibodies, while the cell-mediated response was evaluated by a whole-blood test quantifying the interferon (IFN)-γ-response to spike peptides. FACS analysis was performed to identify the cells responding to spike stimulation. RA disease activity was evaluated by clinical examination through the DAS28crp, and local and/or systemic clinical adverse events were registered. In RA patients, the ongoing therapeutic regimen was modified during the vaccination period according to the American College of Rheumatology indications. Results: We prospectively enrolled 167 HCWs and 35 RA patients. Anti-RBD-antibodies were detected in almost all patients (34/35, 97%), although the titer was significantly reduced in patients under CTLA-4-inhibitors (median: 465 BAU/mL, IQR: 103-1189, p<0.001) or IL-6-inhibitors (median: 492 BAU/mL, IQR: 161-1007, p<0.001) compared to HCWs (median: 2351 BAU/mL, IQR: 1389-3748). T-cell-specific response scored positive in most of RA patients [24/35, (69%)] with significantly lower IFN-γ levels in patients under biological therapy such as IL-6-inhibitors (median: 33.2 pg/mL, IQR: 6.1-73.9, p<0.001), CTLA-4-inhibitors (median: 10.9 pg/mL, IQR: 3.7-36.7, p<0.001), and TNF-α-inhibitors (median: 89.6 pg/mL, IQR: 17.8-224, p=0.002) compared to HCWs (median: 343 pg/mL, IQR: 188-756). A significant correlation between the anti-RBD-antibody titer and spike-IFN-γ-specific T-cell response was found in RA patients (rho=0.432, p=0.009). IFN-γ T-cell response was mediated by CD4+ and CD8+ T cells. Finally, no significant increase in disease activity was found in RA patients following vaccination. Conclusion: This study showed for the first time that antibody-specific and whole-blood spike-specific T-cell responses induced by the COVID-19 mRNA-vaccine were present in the majority of RA patients, who underwent a strategy of temporary suspension of immunosuppressive treatment during vaccine administration. However, the magnitude of specific responses was dependent on the immunosuppressive therapy administered. In RA patients, BNT162b2 vaccine was safe and disease activity remained stable.


Subject(s)
Antibodies, Viral/immunology , Arthritis, Rheumatoid/therapy , COVID-19 Vaccines/immunology , Immunotherapy/adverse effects , T-Lymphocytes/immunology , Aged , Arthritis, Rheumatoid/immunology , CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/immunology , COVID-19/prevention & control , Female , Humans , Interferon-gamma/immunology , Lymphocyte Count , Male , Middle Aged , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/cytology , Vaccines, Synthetic/immunology
6.
Front Immunol ; 12: 730414, 2021.
Article in English | MEDLINE | ID: covidwho-1376703

ABSTRACT

Antigen-specific immunotherapy (ASI) holds great promise for type 1 diabetes (T1D). Preclinical success for this approach has been demonstrated in vivo, however, clinical translation is still pending. Reasons explaining the slow progress to approve ASI are complex and span all stages of research and development, in both academic and industry environments. The basic four hurdles comprise a lack of translatability of pre-clinical research to human trials; an absence of robust prognostic and predictive biomarkers for therapeutic outcome; a need for a clear regulatory path addressing ASI modalities; and the limited acceptance to develop therapies intervening at the pre-symptomatic stages of disease. The core theme to address these challenges is collaboration-early, transparent, and engaged interactions between academic labs, pharmaceutical research and clinical development teams, advocacy groups, and regulatory agencies to drive a fundamental shift in how we think and treat T1D.


Subject(s)
Antigens/immunology , Autoimmunity , Diabetes Mellitus, Type 1/therapy , Immunotherapy , Animals , Biomarkers/metabolism , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/metabolism , Humans , Immunotherapy/adverse effects
9.
J Immunother Cancer ; 9(7)2021 07.
Article in English | MEDLINE | ID: covidwho-1318086

ABSTRACT

Expanding the US Food and Drug Administration-approved indications for immune checkpoint inhibitors in patients with cancer has resulted in therapeutic success and immune-related adverse events (irAEs). Neurologic irAEs (irAE-Ns) have an incidence of 1%-12% and a high fatality rate relative to other irAEs. Lack of standardized disease definitions and accurate phenotyping leads to syndrome misclassification and impedes development of evidence-based treatments and translational research. The objective of this study was to develop consensus guidance for an approach to irAE-Ns including disease definitions and severity grading. A working group of four neurologists drafted irAE-N consensus guidance and definitions, which were reviewed by the multidisciplinary Neuro irAE Disease Definition Panel including oncologists and irAE experts. A modified Delphi consensus process was used, with two rounds of anonymous ratings by panelists and two meetings to discuss areas of controversy. Panelists rated content for usability, appropriateness and accuracy on 9-point scales in electronic surveys and provided free text comments. Aggregated survey responses were incorporated into revised definitions. Consensus was based on numeric ratings using the RAND/University of California Los Angeles (UCLA) Appropriateness Method with prespecified definitions. 27 panelists from 15 academic medical centers voted on a total of 53 rating scales (6 general guidance, 24 central and 18 peripheral nervous system disease definition components, 3 severity criteria and 2 clinical trial adjudication statements); of these, 77% (41/53) received first round consensus. After revisions, all items received second round consensus. Consensus definitions were achieved for seven core disorders: irMeningitis, irEncephalitis, irDemyelinating disease, irVasculitis, irNeuropathy, irNeuromuscular junction disorders and irMyopathy. For each disorder, six descriptors of diagnostic components are used: disease subtype, diagnostic certainty, severity, autoantibody association, exacerbation of pre-existing disease or de novo presentation, and presence or absence of concurrent irAE(s). These disease definitions standardize irAE-N classification. Diagnostic certainty is not always directly linked to certainty to treat as an irAE-N (ie, one might treat events in the probable or possible category). Given consensus on accuracy and usability from a representative panel group, we anticipate that the definitions will be used broadly across clinical and research settings.


Subject(s)
Drug-Related Side Effects and Adverse Reactions/diagnosis , Immune Checkpoint Inhibitors/adverse effects , Immunotherapy/adverse effects , Nervous System Diseases/diagnosis , Practice Guidelines as Topic , Consensus , Humans , Nervous System Diseases/chemically induced , Nervous System Diseases/immunology , Neurologists/statistics & numerical data , Oncologists/statistics & numerical data , Patient Care Team/organization & administration , Patient Care Team/statistics & numerical data
10.
J Immunother Cancer ; 9(6)2021 06.
Article in English | MEDLINE | ID: covidwho-1266400

ABSTRACT

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. COVID-19 has highly variable disease severity and a bimodal course characterized by acute respiratory viral infection followed by hyperinflammation in a subset of patients with severe disease. This immune dysregulation is characterized by lymphocytopenia, elevated levels of plasma cytokines and proliferative and exhausted T cells, among other dysfunctional cell types. Immunocompromised persons often fare worse in the context of acute respiratory infections, but preliminary data suggest this may not hold true for COVID-19. In this review, we explore the effect of SARS-CoV-2 infection on mortality in four populations with distinct forms of immunocompromise: (1) persons with hematological malignancies (HM) and hematopoietic stem cell transplant (HCT) recipients; (2) solid organ transplant recipients (SOTRs); (3) persons with rheumatological diseases; and (4) persons living with HIV (PLWH). For each population, key immunological defects are described and how these relate to the immune dysregulation in COVID-19. Next, outcomes including mortality after SARS-CoV-2 infection are described for each population, giving comparisons to the general population of age-matched and comorbidity-matched controls. In these four populations, iatrogenic or disease-related immunosuppression is not clearly associated with poor prognosis in HM, HCT, SOTR, rheumatological diseases, or HIV. However, certain individual immunosuppressants or disease states may be associated with harmful or beneficial effects, including harm from severe CD4 lymphocytopenia in PLWH and possible benefit to the calcineurin inhibitor ciclosporin in SOTRs, or tumor necrosis factor-α inhibitors in persons with rheumatic diseases. Lastly, insights gained from clinical and translational studies are explored as to the relevance for repurposing of immunosuppressive host-directed therapies for the treatment of hyperinflammation in COVID-19 in the general population.


Subject(s)
COVID-19 , Drug Repositioning , Immunocompromised Host , Immunosuppressive Agents/therapeutic use , Immunotherapy , COVID-19/epidemiology , COVID-19/immunology , COVID-19/therapy , Comorbidity , Drug Repositioning/methods , Drug Repositioning/statistics & numerical data , HIV Infections/epidemiology , HIV Infections/immunology , Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/statistics & numerical data , Humans , Immunocompromised Host/physiology , Immunotherapy/adverse effects , Immunotherapy/methods , Immunotherapy/statistics & numerical data , Mortality , Pandemics , Prognosis , Rheumatic Diseases/epidemiology , SARS-CoV-2/physiology , Transplant Recipients/statistics & numerical data
11.
J Immunother Cancer ; 9(5)2021 05.
Article in English | MEDLINE | ID: covidwho-1228897

ABSTRACT

COVID-19, the syndrome caused by the infection with SARS-CoV-2 coronavirus, is characterized, in its severe form, by interstitial diffuse pneumonitis and acute respiratory distress syndrome (ARDS). ARDS and systemic manifestations of COVID-19 are mainly due to an exaggerated immune response triggered by the viral infection. Cytokine release syndrome (CRS), an inflammatory syndrome characterized by elevated levels of circulating cytokines, and endothelial dysfunction are systemic manifestations of COVID-19. CRS is also an adverse event of immunotherapy (IMTX), the treatment of diseases using drugs, cells, and antibodies to stimulate or suppress the immune system. Graft-versus-host disease complications after an allogeneic stem cell transplant, toxicity after the infusion of chimeric antigen receptor-T cell therapy and monoclonal antibodies can all lead to CRS. It is hypothesized that anti-inflammatory drugs used for treatment of CRS in IMTX may be useful in reducing the mortality in COVID-19, whereas IMTX itself may help in ameliorating effects of SARS-CoV-2 infection. In this paper, we focused on the potential shared mechanisms and differences between COVID-19 and IMTX-related toxicities. We performed a systematic review of the clinical trials testing anti-inflammatory therapies and of the data published from prospective trials. Preliminary evidence suggests there might be a benefit in targeting the cytokines involved in the pathogenesis of COVID-19, especially by inhibiting the interleukin-6 pathway. Many other approaches based on novel drugs and cell therapies are currently under investigation and may lead to a reduction in hospitalization and mortality due to COVID-19.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , COVID-19/therapy , Cytokine Release Syndrome/drug therapy , Immunotherapy/methods , Interleukin-6/antagonists & inhibitors , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/pathology , Cytokine Release Syndrome/pathology , Humans , Immunization, Passive/methods , Immunotherapy/adverse effects , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Interleukin-1beta/blood , Interleukin-6/blood , Nitriles , Pyrazoles/therapeutic use , Pyrimidines , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Tumor Necrosis Factor-alpha/blood
12.
Expert Rev Anticancer Ther ; 21(9): 1055-1066, 2021 09.
Article in English | MEDLINE | ID: covidwho-1221423

ABSTRACT

Background: Cancer patients are more vulnerable to Coronavirus disease-2019 (COVID-19) and have a higher risk of adverse outcomes than the general population. Therefore, it is necessary to evaluate whether anti-cancer therapies such as surgery, chemotherapy, immunotherapy, and targeted therapy will increase the severity and mortality of cancer patients with COVID-19.Methods: Relevant articles were retrieved from PubMed, Embase, Web of Science, Cochrane Library and China National Knowledge Infrastructure (CNKI). The search time was from December 1, 2019 to January 23, 2021. Meta-analysis was conducted using Revman 5.3 statistical software.Results: A total of 26 studies were included in this meta-analysis, involving 5571 cancer patients infected with SARS-CoV-2. Meta-analysis showed that surgery, chemotherapy, immunotherapy and targeted therapy were not associated with disease severity or mortality (107/688, OR =1.30, 95% CI[0.79, 2.13], P =0.30; 1956/2674, OR =1.27, 95% CI [0.95, 1.69], P =0.10; 342/1455, OR =1.20, 95% CI [0.90, 1.61], P =0.21; 503/1378, OR =0.92, 95% CI [0.72, 1.19], P =0.54, respectively).Conclusion: In cancer patients with COVID-19, anti-cancer therapy had no adverse effect on disease severity or mortality. Further research is necessary to determine the complex interrelationship between anti-cancer therapy, particularly chemotherapy, and COVID-19.


Subject(s)
COVID-19/complications , Neoplasms/therapy , Humans , Immunotherapy/adverse effects , Immunotherapy/methods , Molecular Targeted Therapy/adverse effects , Molecular Targeted Therapy/methods , Neoplasms/pathology , Neoplasms/virology , Severity of Illness Index
13.
Curr Opin Neurol ; 33(5): 545-552, 2020 10.
Article in English | MEDLINE | ID: covidwho-1219145

ABSTRACT

PURPOSE OF REVIEW: To provide an update on immunomodulating and immunosuppressive therapies in myasthenia gravis and highlight newly approved, or pending approval, therapies with new biologics. RECENT FINDINGS: Preoperative IVIg is not needed to prevent myasthenic crisis in stable myasthenia gravis patients scheduled for surgery under general anesthesia, based on controlled data. Rituximab, if initiated early in new-onset myasthenia gravis, can lead to faster and more sustained remission even without immunotherapies in 35% of patients at 2 years. Biomarkers determining the timing for follow-up infusions in Rituximab-responding AChR-positive patients are discussed. Most patients with MuSK-positive myasthenia gravis treated with Rituximab have sustained long-term remission with persistent reduction of IgG4 anti-MuSK antibodies. Eculizumb in the extension REGAIN study showed sustained long-term pharmacological remissions and reduced exacerbations. Three new biologic agents showed promising results in phase-II controlled myasthenia gravis trials: Zilucoplan, a subcutaneous macrocyclic peptide inhibiting complement C5; Efgartigimod, an IgG1-derived Fc fragment binding to neonatal FcRn receptor; and Rozanolixizumab, a high-affinity anti-FcRn monoclonal antibody. Finally, the safety of ongoing myasthenia gravis immunotherapies during COVID19 pandemic is discussed. SUMMARY: New biologics against B cells, complement and FcRn receptor, are bringing us closer to successful targeted immunotherapies in the chronic management of myasthenia gravis promising an exciting future for antibody-mediated neurological diseases.


Subject(s)
Immunologic Factors/therapeutic use , Immunotherapy/methods , Myasthenia Gravis/drug therapy , Autoantibodies/immunology , COVID-19 , Humans , Immunologic Factors/adverse effects , Immunotherapy/adverse effects , Myasthenia Gravis/immunology , SARS-CoV-2
14.
Clin Med (Lond) ; 21(2): e212-e222, 2021 03.
Article in English | MEDLINE | ID: covidwho-1215724

ABSTRACT

Use of immune checkpoint inhibitors in cancer treatment has increased vastly over the past decade, as both single and combination agent therapies. While having a positive impact on survival rates, adverse effects have been noted, with endocrine effects in around 10% of patients. Thyroid disease and hypophysitis are the most commonly encountered, with diabetes mellitus and primary adrenal insufficiency also reported, as well as more rare endocrinopathies. Patient and clinician education to raise awareness of these effects, as well as regular monitoring to enable early recognition, diagnosis and prompt treatment of the immune side effects, are key. In this review, we discuss the aetiology, presentation and management of the endocrine complications of immunotherapies that are relevant to the general physician, as well as highlighting important areas where further research is still needed.


Subject(s)
Addison Disease , Drug-Related Side Effects and Adverse Reactions , Endocrine System Diseases , Hypophysitis , Neoplasms , Thyroid Diseases , Humans , Hypophysitis/chemically induced , Immunotherapy/adverse effects
15.
J Immunother Cancer ; 9(4)2021 04.
Article in English | MEDLINE | ID: covidwho-1209683

ABSTRACT

The clinically indistinguishable overlap between pneumonitis caused due to immune checkpoint inhibition (ICI) and pneumonia associated with COVID-19 has posed considerable challenges for patients with cancer and oncologists alike. The cancer community continues to face the challenges that lay at the complex immunological intersection of immune-based cancer therapy and immune dysregulation that results from COVID-19. Is there compounded immune dysregulation that could lead to poor outcomes? Could ICIs, in fact, ameliorate SARS-CoV-2-driven T-cell exhaustion?A little more is known about the kinetics of the viral replication in immunocompromised patients now as compared with earlier during the pandemic. Working knowledge of the diagnostic and therapeutic nuances of SARS-CoV-2 infection in patients with active cancers, issues related to viability and replication potential of the virus, unclear role of corticosteroids among those with diminished or dysfunctional effector T-cell repertoire, and the type of immunotherapy with differential risk of pneumonitis will inform decision making related to immunotherapy choices and decision for ICI continuation in the era of COVID-19.


Subject(s)
COVID-19/immunology , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy/methods , Neoplasms/therapy , Pneumonia/immunology , SARS-CoV-2/immunology , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/therapeutic use , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Diagnosis, Differential , Humans , Immune Checkpoint Inhibitors/adverse effects , Immunocompromised Host/immunology , Immunotherapy/adverse effects , Neoplasms/immunology , Pneumonia/chemically induced , Pneumonia/diagnosis , SARS-CoV-2/physiology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
16.
Am J Hematol ; 96(8): 934-944, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1204615

ABSTRACT

Prolonged Covid-19 is an emerging issue for patients with lymphoma or immune deficiency. We aimed to examine prolonged length of in-hospital stay (LOS) due to Covid-19 among patients with lymphoma and assess its determinants and outcomes. Adult patients with lymphoma admitted for Covid-19 to 16 French hospitals in March and April, 2020 were included. Length of in-hospital stay was analyzed as a competitor vs death. The study included 111 patients. The median age was 65 years (range, 19-92). Ninety-four patients (85%) had B-cell non-Hodgkin lymphoma. Within the 12 months prior to hospitalization for Covid-19, 79 patients (71%) were treated for their lymphoma. Among them, 63 (57%) received an anti-CD20 therapy. Fourteen patients (12%) had relapsed/refractory disease. The median LOS was 14 days (range, 1-235). After a median follow-up of 191 days (3-260), the 6-month overall survival was 69%. In multivariable analyses, recent administration of anti-CD20 therapy was associated with prolonged LOS (subdistribution hazard ratio 2.26, 95% confidence interval 1.42-3.6, p < 0.001) and higher risk of death (hazard ratio 2.17, 95% confidence interval 1.04-4.52, p = 0.039). An age ≥ 70 years and relapsed/refractory lymphoma were also associated with prolonged LOS and decreased overall survival. In conclusion, an age ≥ 70 years, a relapsed/refractory lymphoma and recent administration of anti-CD20 therapy are risk factors for prolonged LOS and death for lymphoma patients hospitalized for Covid-19. These findings may contribute to guide the management of lymphoma during the pandemic, support evaluating specific therapeutic approaches, and raise questions on the efficacy and timing of vaccination of this particular population.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , B-Lymphocytes/drug effects , COVID-19/complications , Immunotherapy/adverse effects , Length of Stay/statistics & numerical data , Lymphoma, Non-Hodgkin/complications , SARS-CoV-2 , Adult , Age Factors , Aged , Aged, 80 and over , Antigens, CD20/immunology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , COVID-19/mortality , Combined Modality Therapy , Comorbidity , Drug Resistance, Neoplasm , Female , Humans , Lymphoma, Non-Hodgkin/mortality , Lymphoma, Non-Hodgkin/therapy , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk Factors , Rituximab/administration & dosage , Rituximab/adverse effects , Survival Analysis , Young Adult
17.
Gerontology ; 67(4): 379-385, 2021.
Article in English | MEDLINE | ID: covidwho-1158148

ABSTRACT

BACKGROUND: Older cancer patients with locally advanced or metastatic disease may benefit from chemotherapy alone or combined with radiotherapy. However, chemotherapy is often omitted either because of physician bias or because of its underlying comorbidity, thus compromising their survival. The coronavirus disease 19 (COVID-19) pandemic is compounding this issue because of the fear of immunosuppression induced by chemotherapy on the elderly which makes them more vulnerable to the virus. SUMMARY: Immunotherapy has less effect on the patient bone marrow compared to chemotherapy. The potential synergy between radiotherapy and immunotherapy may improve local control and survival for older patients with selected cancer. Preliminary data are encouraging because of better survival and local control in diseases which are traditionally resistant to radiotherapy and chemotherapy such as melanoma and renal cell carcinoma. Key Message: We propose a new paradigm combining immunotherapy at a reduced dose and/or extended dosing intervals and hypofractionated radiotherapy for older patients with selected cancer which needs to be tested in future clinical trials.


Subject(s)
COVID-19/complications , Immunotherapy/adverse effects , Neoplasms/radiotherapy , Aged , Bone Marrow/immunology , Bone Marrow/physiopathology , Combined Modality Therapy , Humans
18.
Curr Opin Neurol ; 34(3): 295-302, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1158063

ABSTRACT

PURPOSE OF REVIEW: Treatments targeting B cells are increasingly used for patients with multiple sclerosis (MS). We review the mechanisms of action, clinical effectiveness and safety of treatment, with emphasis on recently published studies. RECENT FINDINGS: Several monoclonal antibodies targeting the surface molecule CD20 on B cells are approved or being developed for treatment of MS. Overall, they seem comparable in terms of strongly suppressing radiological disease activity and relapse biology. Novel approaches include anti-CD19 antibody therapy and treatment with oral drugs targeting Bruton's tyrosine kinase (BTK). The main safety issue with persistent B cell depletion is an increased risk of infections - possibly including an increased risk of severe COVID-19. Vaccine responses are also blunted in patients treated with anti-CD20 antibodies. Lower doses or longer infusion intervals may be sufficient for control of disease activity. Whether this might also improve the safety of treatment and increase vaccination responses remains to be determined. SUMMARY: Available data support the widespread use of therapies targeting B cells in MS. Whether novel approaches targeting CD19 or BTK will have advantages compared to anti-CD20 antibody therapy remains to be established. Furthermore, trials investigating alternative dosing regimens for anti-CD20 antibody treatment are warranted.


Subject(s)
B-Lymphocytes/immunology , Immunotherapy/adverse effects , Immunotherapy/methods , Multiple Sclerosis/therapy , Antibodies, Monoclonal/therapeutic use , COVID-19/complications , Humans , Infection Control , Multiple Sclerosis/complications , Risk
19.
Ann Oncol ; 32(7): 866-880, 2021 07.
Article in English | MEDLINE | ID: covidwho-1152247

ABSTRACT

BACKGROUND: Based on favourable outcomes in clinical trials, immune checkpoint inhibitors (ICIs), most notably programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors, are now widely used across multiple cancer types. However, due to their strict inclusion and exclusion criteria, clinical studies often do not address challenges presented by non-trial populations. DESIGN: This review summarises available data on the efficacy and safety of ICIs in trial-ineligible patients, including those with autoimmune disease, chronic viral infections, organ transplants, organ dysfunction, poor performance status, and brain metastases, as well as the elderly, children, and those who are pregnant. In addition, we review data concerning other real-world challenges with ICIs, including timing of therapy switch, relationships to radiotherapy or surgery, re-treatment after an immune-related toxicity, vaccinations in patients on ICIs, and current experience around ICI and coronavirus disease-19. Where possible, we provide recommendations to aid the often-difficult decision-making process in those settings. CONCLUSIONS: Data suggest that ICIs are often active and have an acceptable safety profile in the populations described above, with the exception of PD-1 inhibitors in solid organ transplant recipients. Decisions about whether to treat with ICIs should be personalised and require multidisciplinary input and careful counselling of patients with respect to potential risks and benefits. Clinical judgements need to be carefully weighed, considering factors such as underlying cancer type, feasibility of alternative treatment options, or activity in trial-eligible patients.


Subject(s)
COVID-19 , Neoplasms , Aged , Child , Humans , Immunologic Factors , Immunotherapy/adverse effects , Neoplasms/therapy , SARS-CoV-2
20.
Curr Opin Neurol ; 34(3): 322-328, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1132693

ABSTRACT

PURPOSE OF REVIEW: This review focuses on new evidence supporting the global immunization strategy for multiple sclerosis (MS) patients receiving disease-modifying drugs (DMDs), including the recently available vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RECENT FINDINGS: New data strengthen the evidence against a causal link between MS and vaccination. Recent consensus statements agree on the need to start vaccination early. Timings for vaccine administration should be adjusted to ensure safety and optimize vaccine responses, given the potential interference of DMDs. Patients treated with Ocrelizumab (and potentially other B-cell depleting therapies) are at risk of diminished immunogenicity to vaccines. This has relevant implications for the upcoming vaccination against SARS-CoV-2. SUMMARY: An early assessment and immunization of MS patients allows optimizing vaccine responses and avoiding potential interference with treatment plans. Vaccinations are safe and effective but some specific considerations should be followed when vaccinating before, during, and after receiving immunotherapy. A time-window for vaccination taking into account the kinetics of B cell repopulation could potentially improve vaccine responses. Further understanding of SARS-CoV-2 vaccine response dynamics in MS patients under specific therapies will be key for defining the best vaccination strategy.


Subject(s)
Antirheumatic Agents/therapeutic use , Immunization Programs/organization & administration , Multiple Sclerosis/drug therapy , Multiple Sclerosis/immunology , Antirheumatic Agents/adverse effects , COVID-19 Vaccines/therapeutic use , Humans , Immunotherapy/adverse effects , Immunotherapy/methods , Vaccination , Viral Vaccines/adverse effects , Viral Vaccines/immunology
SELECTION OF CITATIONS
SEARCH DETAIL