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Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Alemtuzumab is approved by the FDA as a single agent for the first-line treatment of B-cell chronic lymphocytic leukemia (B-CLL). In other countries it is approved for B-CLL in patients who have been previously treated with alkylating agents and for whom fludarabine combination therapy is not appropriate. Alemtuzumab is also used in the treatment of Cutaneous T-Cell Lymphoma (CTCL) and T-Cell Lymphoma, and as second-line therapy for CLL. In some countries the use of alemtuzumab is restricted to those patients with previously untreated B-CLL and who have the cytogenetic 17p-deletion abnormality. It is also used in some conditioning regimens for bone marrow and kidney transplants, and is presently in clinical trials for the treatment of autoimmune diseases including multiple sclerosis and graft-versus-host disease. It is marketed by Genzyme (acquired by Sanofi in 2011), which obtained worldwide rights from Bayer AG in 2009. In 2012 CampathTM was withdrawn from both the US and European markets to prevent off-label use of the drug for multiple sclerosis in preparation for a re-launch using a different dosage under the trade name LemtradaTM (approved in 2014) aimed specifically at the multiple sclerosis market.
Central nervous system viral infections complicating immunosuppression
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Alemtuzumab is a humanized monoclonal antibody to the cell surface molecule CD52 present on both T and B cells. Profound depletion of both cell types occurs. The drug has been associated with PML (Table 24.4) in lymphoma and leukemia patients receiving alemtuzumab but as of this date not in MS patients. Cases of severe neutropenia within four to six weeks after alemtuzumab have been reported and vigilance for this complication with frequent complete blood counts in the first two months is recommended [34]. Recently, it has been shown that B cells repopulate more rapidly than regulatory T cells, a sequence that may explain the frequent autoimmune diseases that occur with this drug [35].
Infection in the Hematopoeitic Stem Cell Transplant Recipient with Autoimmune Disease
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Valentina Stosor, Teresa R. Zembower
Alemtuzumab, also known as CAMPATH-1H which is named after where it was developed, Cambridge University’s department of pathology, is a humanized monoclonal anti-CD52 antibody increasingly used in conditioning regimens.80 Although its exact mechanism of action is unknown, treatment with alemtuzumab results in profound B- and T-lymphopenia.83 For this reason, when combined with aggressive immune suppressive conditioning agents, alemtuzumab-treated patients are at risk for the development of OIs such as those caused by herpesviruses, Candida species, invasive molds, P. carinii, and bacterial pathogens.83-86
Safety considerations with the current treatments for peripheral T-cell lymphoma
Published in Expert Opinion on Drug Safety, 2022
Tarsheen Sethi, Francesca Montanari, Francine Foss
The CD52 antigen is a glycosylphosphatidylinositol-linked protein expressed at high density on the cell surface of normal and malignant lymphocytes, including most T-cell lymphoma subtypes. Alemtuzumab is an anti-CD52 monoclonal antibody with a human IgG1 immunoglobulin (IgG1) gene which has shown significant efficacy against T-PLL and other subtypes of T cell lymphomas [28,29]. In a pilot study evaluating alemtuzumab in R/R PTCL (n = 14), the ORR was 36%. The most common side effects were CMV reactivation (n = 6), pancytopenia (n = 4), pulmonary aspergillosis (n = 2) and HLH related to EBV (n = 2). Of note, in this study all patients received trimethoprim/sulfamethoxazole and valacyclovir prophylaxis [29]. A combination of alemtuzumab with CHOP (A-CHOP) was investigated in three non-randomized phase 2 trials, documenting feasibility of this approach, and suggesting clinical benefit [30–32]. The DSHNHL2006-1B/ACT-2 trial (n = 116) evaluated A-CHOP in patients 61–80 years of age and found the combination to be associated with more grade 3/4 infections (40% vs. 21%) and infection-related deaths (4 vs.1) compared with CHOP. The ORR was superior with A-CHOP (72% vs. 66%) without an improvement in OS due to toxicity [31]. In summary, alemtuzumab is an effective drug for T-cell lymphomas, however, due to increased risk of infections is often used after failure of multiple lines of therapy.
Emerging therapeutic targets for narcolepsy
Published in Expert Opinion on Therapeutic Targets, 2021
Marieke Vringer, Birgitte Rahbek Kornum
Finally, monoclonal antibody treatment has been attempted in NT1. Natalizumab inhibits the migration of immune cells into the brain and if NT1 is driven by an ongoing entry of autoreactive T cells to CNS, natalizumab would in theory dampen the autoimmune destruction of Hcrt neurons. However, natalizumab showed no effect on clinical symptoms and CSF Hcrt-1 levels in a NT1 patient [145]. The monoclonal antibody rituximab has an immunosuppressive effect via depletion of B-cells [14,146]. A dramatic improvement of NT1 symptoms was reported in a case report of a 12-year-old patient following rituximab treatment, but the improvement lasted only 2 months [146]. Another NT1 patient experienced less EDS but no improvement of cataplexy or CSF Hcrt-1 levels after rituximab treatment [147]. Alemtuzumab can inhibit an autoimmune response by depleting both circulating T- and B-cells. Complete disappearance of cataplexy was reported in a 68-years-old NT1 patient following alemtuzumab treatment, but all his other clinical symptoms remained unchanged [148].
Expert consensus from the Arabian Gulf on selecting disease-modifying treatment for people with multiple sclerosis according to disease activity
Published in Postgraduate Medicine, 2020
Raed Alroughani, Jihad Inshasi, Abdullah Al-Asmi, Abdulradha Alqallaf, Abdulla Al Salti, Ahmed Shatila, Amir Boshra, Beatriz Canibano, Dirk Deleu, Isa Al Sharoqi, Jaber Al Khabouri
No choice of third-line treatment is evidence based, due to the lack of well-designed clinical trials based on patients who have received two DMDs previously, and so these recommendations are from the experience and judgment of the authors. It is reasonable that a patient with breakthrough activity on two previous DMDs will need the most effective therapy available. For this reason, DMF is omitted from this category, and ocrelizumab and alemtuzumab are added. A recent network meta-analysis found comparable efficacy for suppression of relapses and progression of disability between other highly effective DMDs [49], which adds support to this approach. The prescribing of alemtuzumab has been restricted in Europe to patients with highly active disease, with new contraindications relating to concomitant autoimmune and cardiovascular conditions (see Tables 1 and 2).