Alemtuzumab 30mg/1ml solution for infusion vials

This article analyses the presence of gender bias in clinical trials of monoclonal antibodies used to treat multiple sclerosis. We performed a systematic review of controlled clinical trials of 4 monoclonal antibodies used to treat multiple sclerosis (natalizumab, rituximab, alemtuzumab, and ocrelizumab). We searched the PubMed/MEDLINE database for articles published in English before March 2020. The study was conducted in accordance with the relevant international recommendations. The search identified 89 articles, 55 of which met the inclusion criteria. Of all patients included in these trials, 64.6% were women. The lead authors of 10 of the studies were women. Fifteen of the 55 studies included a sex-based analysis of the primary endpoint. Only 8 articles discussed the results separately for men and for women. The clinical trials of these 4 monoclonal antibodies present a significant gender bias. In most cases, the primary and secondary endpoints are not analyzed according to patient sex, despite the fact that international recommendations include this as a minimum requirement for ensuring scientific validity and obtaining appropriate results for extrapolation to the wider population. Este artículo evalúa el sesgo de género presente en los ensayos clínicos sobre anticuerpos monoclonales para el tratamiento de la esclerosis múltiple. Se realizó una revisión sistemática de ensayos clínicos controlados de 4 anticuerpos monoclonales (natalizumab, rituximab, alemtuzumab y ocrelizumab) para el tratamiento de la esclerosis múltiple a través de las bases de datos Pubmed/Medline, publicados hasta marzo de 2020 y los cuales fueron escritos en inglés. El estudio siguió las correspondientes recomendaciones internacionales. Se identificaron 89 artículos, de los cuales 55 cumplieron los criterios de inclusión. Se encontró que el 64,6% del total de pacientes eran mujeres. El sexo del primer autor era femenino en 10 ensayos clínicos. El análisis de la variable principal en función del sexo se realizó en 15 de los 55 artículos incluidos. Además, solo 8 ensayos clínicos discutieron los resultados separadamente de acuerdo al sexo. Los ensayos clínicos de estos 4 anticuerpos monoclonales muestran un sesgo de género significativo. En su mayoría, la variable principal y secundarias no son analizadas en función del sexo. Esto se produce a pesar de las recomendaciones internacionales que lo establecen, como requisito mínimo, para dar validez científica y obtener unos resultados apropiados para extender su aplicación a la población global.

Abstract licence: CC BY-NC-ND

OBJECTIVE: To evaluate 5-year efficacy and safety of alemtuzumab in patients with active relapsing-remitting multiple sclerosis and inadequate response to prior therapy. METHODS: In the 2-year Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II study (NCT00548405), alemtuzumab-treated patients received 2 courses (baseline and 12 months later). Patients could enter an extension (NCT00930553), with as-needed alemtuzumab retreatment for relapse or MRI activity. Annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale [EDSS] score increase [≥1.5 if baseline EDSS = 0]), 6-month confirmed disability improvement (CDI; ≥1-point EDSS decrease [baseline score ≥2.0]), no evidence of disease activity (NEDA), brain volume loss (BVL), and adverse events (AEs) were assessed. RESULTS: Most alemtuzumab-treated patients (92.9%) who completed CARE-MS II entered the extension; 59.8% received no alemtuzumab retreatment. ARR was low in each extension year (years 3-5: 0.22, 0.23, 0.18). Through 5 years, 75.1% of patients were free of 6-month CDW; 42.9% achieved 6-month CDI. In years 3, 4, and 5, proportions with NEDA were 52.9%, 54.2%, and 58.2%, respectively. Median yearly BVL remained low in the extension (years 1-5: -0.48%, -0.22%, -0.10%, -0.19%, -0.07%). AE exposure-adjusted incidence rates in the extension were lower than in the core study. Thyroid disorders peaked at year 3, declining thereafter. CONCLUSIONS: Alemtuzumab provides durable efficacy through 5 years in patients with an inadequate response to prior therapy in the absence of continuous treatment. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that alemtuzumab provides efficacy and slowing of brain atrophy through 5 years.

Abstract licence: CC BY-NC-ND

Alemtuzumab is a humanized recombinant monoclonal antibody that specifically targets the CD52 antigen, which is expressed on both malignant and normal T and B lymphocytes. By binding to CD52, alemtuzumab exerts potent antitumor and immunosuppressive effects. Initially approved by the FDA in 2001 for the treatment of B-cell chronic lymphocytic leukemia (B-CLL), alemtuzumab's therapeutic applications have expanded to various hematologic malignancies, including lymphoma, acute leukemia, myelodysplastic syndromes (MDS), aplastic anemia (AA), graft-versus-host disease (GVHD), and chimeric antigen receptor T-cell (CAR-T) therapy. This review evaluates the efficacy and safety of alemtuzumab in these conditions, aiming to synthesize current evidence and provide guidance for clinical practice to optimize the use of alemtuzumab in the treatment of these diseases.

Abstract licence: CC BY-NC-ND

T-cell prolymphocytic leukemia is a rare and aggressive mature T-cell malignancy that usually presents with marked lymphocytosis, hepatosplenomegaly, lymphadenopathy, and B symptoms. However, a minority of patients present with an indolent, asymptomatic form. Case Report: A 44-year-old man was diagnosed with asymptomatic T-cell prolymphocytic leukemia after routine blood tests revealed persistent lymphocytosis. Immunophenotyping revealed a mature CD4-/CD8+ T-cell population. Cytogenetic analysis showed 14q11.2 abnormalities with TCRAD rearrangement by fluorescent in situ hybridization. A monoclonal T-cell population was confirmed by flow cytometry and polymerase chain reaction, and a STAT5B mutation was identified by next-generation sequencing. The patient had no cytopenia or organ involvement and a watch-and-wait strategy was adopted. The pathogenesis of T-cell prolymphocytic leukemia involves recurrent genetic alterations, including TCL1A rearrangements and ATM mutations, which promote genomic instability. Despite their aggressive nature, up to 30% of cases initially follow an indolent course, allowing for observation rather than immediate treatment. Standard therapies include alemtuzumab-based regimens and hematopoietic stem cell transplantation, although relapse rates remain high. Conclusion: This case underscores the need to recognize indolent presentations of T-cell prolymphocytic leukemia that may be managed conservatively. Further research is required to identify prognostic markers and optimize therapeutic strategies.

Abstract licence: CC BY