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Multiple Sclerosis and Related Disorders Jun 2021The SARS-CoV-2 pandemic impact on people with Multiple Sclerosis (pwMS) continues to worry. The disease modifying therapies in pwMS can add a more severe risk of...
BACKGROUND
The SARS-CoV-2 pandemic impact on people with Multiple Sclerosis (pwMS) continues to worry. The disease modifying therapies in pwMS can add a more severe risk of infection when compared to the general population. Alemtuzumab is an anti-CD52 monoclonal antibody and it is one of the most immunosuppressive drugs used in Multiple Sclerosis (MS).
CASE DESCRIPTION
We present a case of Covid-19 infection that occurred in a 24-year-old woman with MS and treated with alemtuzumab. The infection occurred 4 months after administration of the first course of alemtuzumab and had a benign course with subsequent development of antibodies. Furthermore, we present a brief review of the literature on similar published cases.
DISCUSSION
We reviewed 17 articles concerning COVID-19 infection in MS patients in treatment with Alemtuzumab. In our case and all screened cases no severe course of disease was noted and no fatality was observed. Systematic compilation of this observation comforts clinicians about the course of Covid-19 infection despite alemtuzumab immunosuppressive treatment CONCLUSIONS: The risk of serious COVID-19 disease in MS patients treated with alemtuzumab is unknown. Physicians need to monitor carefully pwMS treated with alemtuzumab and to consider COVID-19 infection related relapse in the MS patients. Further research is recommended to evaluate the beneficial-risk profile of alemtuzumab in pandemic era.
Topics: Adult; Alemtuzumab; COVID-19; Female; Humans; Multiple Sclerosis; Pandemics; SARS-CoV-2; Young Adult
PubMed: 33812222
DOI: 10.1016/j.msard.2021.102908 -
Multiple Sclerosis and Related Disorders Jul 2023Alemtuzumab is a highly effective treatment for relapsing remitting multiple sclerosis (RRMS), but in recent years safety-related concerns had emerged due to description... (Observational Study)
Observational Study
BACKGROUND
Alemtuzumab is a highly effective treatment for relapsing remitting multiple sclerosis (RRMS), but in recent years safety-related concerns had emerged due to description of novel serious side effects not registered in CARE-MS I and CARE-MS II phase 3 studies, nor in TOPAZ extension study. Data about alemtuzumab use in real clinical practice are limited and based mainly on retrospective studies with small sample sizes. Therefore, more information about effectiveness and safety of alemtuzumab in this context is needed.
METHODS
A multicenter observational prospective study to investigate effectivity and safety of alemtuzumab in a real-world setting was performed. Primary endpoints were the change in annualized relapse rate (ARR), and in disability measured by EDSS score. Secondary endpoints were the cumulative probability of confirmed 6-month disability improvement and worsening. Disability worsening and disability improvement were considered when the EDSS score was increased or decreased, respectively, in 1 point if baseline EDSS score was <5.0, or in 0.5 point if baseline EDSS score was ≥5.5, confirmed over 6 months. Other secondary endpoint was the proportion of patients who achieved NEDA-3 status (absence of clinical relapses, disability EDSS progression, and MRI disease activity as depicted by new/enlarging T2 lesions or Gadolinium enhancing T1 lesions). Adverse events also were recorded.
RESULTS
A total of 195 RRMS patients (70% female) who started alemtuzumab treatment were included. Mean of follow-up was 2.38 years. Alemtuzumab significantly reduced the annualized relapse rate from baseline with risk reductions of 86%, 83.5%, and 84%, at 12, 24, and 36 months of follow-up respectively (Friedman test, p-value < 0.05 for all comparisons). Alemtuzumab also significantly reduced EDSS score over one and two years after starting alemtuzumab treatment (Friedman test, p-value<0.001 for both comparisons). A high proportion of patients presented confirmed 6-month stability or disability improvement (92%, 82%, and 79%, over 1, 2 and 3 years of follow-up respectively). The proportion of patients who retained NEDA-3 status at 12, 24 and 36 months were 61%, 49%, and 42%, respectively. Baseline characteristics associated with a lower probability of achieving NEDA-3 were younger age, sex female, high ARR, elevated number of previous treatments, and switch from a second line therapy. Infusion related reactions were the most frequent adverse event observed. The most common infections were urinary tract infections (50%), and upper respiratory tract infections (19%) over the 3 years of follow- up. Secondary thyroid autoimmunity was developed in 18.5% of patients.
CONCLUSION
Alemtuzumab has demonstrated in real clinical practice high effectiveness in controlling multiple sclerosis activity, and no unexpected adverse events were observed.
Topics: Humans; Female; Male; Alemtuzumab; Retrospective Studies; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Recurrence
PubMed: 37229800
DOI: 10.1016/j.msard.2023.104762 -
Pediatrics International : Official... 2023
Topics: Humans; Alemtuzumab; Lymphoproliferative Disorders; Genetic Diseases, X-Linked; Hematopoietic Stem Cell Transplantation; Transplantation Conditioning; Graft vs Host Disease; X-Linked Inhibitor of Apoptosis Protein
PubMed: 37534620
DOI: 10.1111/ped.15576 -
Transplantation Dec 2007Alemtuzumab is a humanized CD52-specific monoclonal antibody that is increasingly used off-label as an induction agent in solid organ transplantation, particularly in...
Alemtuzumab is a humanized CD52-specific monoclonal antibody that is increasingly used off-label as an induction agent in solid organ transplantation, particularly in the setting of maintenance immunosuppression minimization protocols. In this review, we briefly discuss this agent's mechanisms of action and summarize evidence supporting its use in this clinical setting.
Topics: Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Clinical Trials as Topic; Humans; Immunosuppressive Agents; Transplantation Immunology
PubMed: 18165760
DOI: 10.1097/01.tp.0000296680.75175.67 -
Current Neurology and Neuroscience... Sep 2016Alemtuzumab is a humanised anti-CD52 monoclonal antibody approved for use in active, relapsing multiple sclerosis (MS). Administration results in a rapid depletion of... (Review)
Review
Alemtuzumab is a humanised anti-CD52 monoclonal antibody approved for use in active, relapsing multiple sclerosis (MS). Administration results in a rapid depletion of circulating lymphocytes with a subsequent beneficial immune reconstitution. Early open-label experience and recent clinical trials have demonstrated a dramatic effect on relapse rates as well as a positive effect on radiological disease outcomes and disability measures. Despite a mechanism of action that results in profound lymphopaenia, opportunistic infections are rarely seen and no excess association with malignancy has been identified. However, acquired autoimmune disease (AID) is a common adverse event following treatment, necessitating rigorous monitoring in order to facilitate prompt detection and management. Despite this issue, a unique dosing schedule and durability of effect make alemtuzumab a welcome addition to currently available treatment options for MS.
Topics: Alemtuzumab; Animals; Antibodies, Monoclonal, Humanized; Autoimmunity; Clinical Trials as Topic; Humans; Multiple Sclerosis; Neoplasms; Recurrence
PubMed: 27485945
DOI: 10.1007/s11910-016-0685-y -
Blood Advances Jul 2023Overall survival after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) using alemtuzumab, fludarabine, and melphalan is...
Overall survival after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) using alemtuzumab, fludarabine, and melphalan is associated with high rates of mixed chimerism (MC) and secondary graft failure (GF). We hypothesized that peritransplantation alemtuzumab levels or specific patterns of inflammation would predict these risks. We assessed samples from the Bone Marrow Transplant Clinical Trials Network 1204 (NCT01998633) to study the impact of alemtuzumab levels and cytokine patterns on MC and impending or established secondary GF (defined as donor chimerism <5% after initial engraftment and/or requirement of cellular intervention). Thirty-three patients with hemophagocytic lymphohistiocytosis (n = 25) and other IEIs (n = 8) who underwent HCTs with T-cell-replete grafts were included. Patients with day 0 alemtuzumab levels ≤0.32 μg/mL had a markedly lower incidence of MC, 14.3%, vs 90.9% in patients with levels >0.32 μg/mL (P = .008). Impending or established secondary GF was only observed in patients with day 0 alemtuzumab levels >0.32 μg/mL (P = .08). Unexpectedly, patients with impending or established secondary GF had lower CXCL9 levels. The cumulative incidence of impending or established secondary GF in patients with a day 14+ CXCL9 level ≤2394 pg/mL (day 14+ median) was 73.6% vs 0% in patients with a level >2394 pg/mL (P = .002). CXCL9 levels inversely correlated with alemtuzumab levels. These data suggest a model in which higher levels of alemtuzumab at day 0 deplete donor T cells, inhibit the graft-versus-marrow reaction (thereby suppressing CXCL9 levels), and adversely affect sustained engraftment in the nonmyeloablative HCT setting. This trial was registered at www.clinicaltrials.gov as #NCT01998633.
Topics: Humans; Alemtuzumab; Antibodies, Monoclonal, Humanized; Melphalan; Hematopoietic Stem Cell Transplantation; Tissue Donors; Chemokine CXCL9
PubMed: 37042921
DOI: 10.1182/bloodadvances.2022009478 -
Brain : a Journal of Neurology Jun 2022Alemtuzumab is a monoclonal antibody that causes rapid depletion of CD52-expressing immune cells. It has proven to be highly efficacious in active relapsing-remitting...
Alemtuzumab is a monoclonal antibody that causes rapid depletion of CD52-expressing immune cells. It has proven to be highly efficacious in active relapsing-remitting multiple sclerosis; however, the high risk of secondary autoimmune disorders has greatly complicated its use. Thus, deeper insight into the pathophysiology of secondary autoimmunity and potential biomarkers is urgently needed. The most critical time points in the decision-making process for alemtuzumab therapy are before or at Month 12, where the ability to identify secondary autoimmunity risk would be instrumental. Therefore, we investigated components of blood and CSF of up to 106 multiple sclerosis patients before and after alemtuzumab treatment focusing on those critical time points. Consistent with previous reports, deep flow cytometric immune-cell profiling (n = 30) demonstrated major effects on adaptive rather than innate immunity, which favoured regulatory immune cell subsets within the repopulation. The longitudinally studied CSF compartment (n = 18) mainly mirrored the immunological effects observed in the periphery. Alemtuzumab-induced changes including increased numbers of naïve CD4+ T cells and B cells as well as a clonal renewal of CD4+ T- and B-cell repertoires were partly reminiscent of haematopoietic stem cell transplantation; in contrast, thymopoiesis was reduced and clonal renewal of T-cell repertoires after alemtuzumab was incomplete. Stratification for secondary autoimmunity did not show clear immununological cellular or proteomic traits or signatures associated with secondary autoimmunity. However, a restricted T-cell repertoire with hyperexpanded T-cell clones at baseline, which persisted and demonstrated further expansion at Month 12 by homeostatic proliferation, identified patients developing secondary autoimmune disorders (n = 7 without secondary autoimmunity versus n = 5 with secondary autoimmunity). Those processes were followed by an expansion of memory B-cell clones irrespective of persistence, which we detected shortly after the diagnosis of secondary autoimmune disease. In conclusion, our data demonstrate that (i) peripheral immunological alterations following alemtuzumab are mirrored by longitudinal changes in the CSF; (ii) incomplete T-cell repertoire renewal and reduced thymopoiesis contribute to a proautoimmune state after alemtuzumab; (iii) proteomics and surface immunological phenotyping do not identify patients at risk for secondary autoimmune disorders; (iv) homeostatic proliferation with disparate dynamics of clonal T- and B-cell expansions are associated with secondary autoimmunity; and (v) hyperexpanded T-cell clones at baseline and Month 12 may be used as a biomarker for the risk of alemtuzumab-induced autoimmunity.
Topics: Alemtuzumab; Autoimmune Diseases; Autoimmunity; Humans; Phenotype; Proteomics
PubMed: 35661859
DOI: 10.1093/brain/awac064 -
Pediatric Transplantation Mar 2018Alemtuzumab is a humanized mAb targeted to CD52. Alemtuzumab is highly immunosuppressive with the ability to deplete T and B cells (in addition to other immune cell... (Review)
Review
Alemtuzumab is a humanized mAb targeted to CD52. Alemtuzumab is highly immunosuppressive with the ability to deplete T and B cells (in addition to other immune cell lines). A growing understanding of the PKs, dosing, and timing of administration of alemtuzumab has allowed for the study of its use as a conditioning agent for allogeneic HCT. The highly immunosuppressive properties of the drug are particularly appealing in the setting of non-malignant HCT, where GVHD provides no clinical benefit and relapse of malignancy is not applicable. In addition, the degree of immune suppression achieved with alemtuzumab has allowed for a reduction in the intensity of myeloablative cytotoxic agents included in some HCT conditioning regimens, allowing for fewer acute and late toxicities. This review paper will provide a comprehensive summary of the mechanism of action, PKs, dosing, and timing of alemtuzumab, a brief description of its use in various allogeneic HCT protocols for non-malignant conditions and a summary of the data regarding its use for GVHD therapy. The goal of this review was to provide an understanding as to how alemtuzumab might be safely incorporated into HCT conditioning regimens for children with non-malignant disease, allowing for expanded access to curative HCT therapy.
Topics: Alemtuzumab; Child; Drug Administration Schedule; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Transplantation Conditioning
PubMed: 29352515
DOI: 10.1111/petr.13142 -
Transplant Infectious Disease : An... Dec 2023
Topics: Humans; Histoplasmosis; Alemtuzumab; Histoplasma; Antifungal Agents
PubMed: 37323093
DOI: 10.1111/tid.14089 -
Multiple Sclerosis (Houndmills,... Nov 2018
Review
Topics: Alemtuzumab; Antibodies, Monoclonal, Humanized; Autoimmunity; Humans; Multiple Sclerosis, Relapsing-Remitting; Sarcoidosis; T-Lymphocytes; Treatment Outcome
PubMed: 30307361
DOI: 10.1177/1352458518804124