Alemtuzumab for

Alemtuzumab has shown impressive results in refractory or relapsed CLL as well as up-front therapy for untreated CLL (35). The use of alemtuzumab to eradicate minimal residual disease of CLL is also reasonable (36). The role of Fey receptor polymorphisms on the clinical activity of alemtuzumab for CLL has not been extensively studies and will be discussed later. 

Verbeek WHM, Mulder CJJ, Zweegman S, Vivas S, et al. 2006. Alemtuzumab for refractory celiac disease. NEJM. 355 1396-1397. 

Vivas S, Morales JM, Ramos F, Suarez-Vilela D. 2006. Alemtuzumab for refractory celiac disease in a patient at risk for enteropathy-associated T-cell lymphoma. NEJM. 354 23-24. 

CHAPTER 51 Antineoplastic Agents 901 solid tumor malignancies, including rituximab and alemtuzumab for lymphoid malignancies, and... 

Gomez-Almaguer D et al. Alemtuzumab for the treatment of steroid-refractory acute graft-versus-host disease. Biology of Blood and Marrow Transplantation 2008 14 10-15. 

Sohani AR, Ferry JA, Chang PS, Abramson IS. Epstein-Barr virus-positive diffuse large B-cell lymphoma during therapy with alemtuzumab for T-cell prolym-phocytic leukemia. J Clin Oncol 2010 28 e69-72. 

In a study of alemtuzumab for the treatment of acute rejection in 15 kidney transplant recipients, the rates of malignancies in alemtuzumab-treated patients were not increased during 12 years follow-up in particular, no patients treated with alemtuzumab for acute rejection developed post-transplantation lymphoproliferative disorders [148 ]. 

Watch for infusion reactions with rituximab and alemtuzumab. Premedicate with acetaminophen and diphenhydramine to prevent these reactions. 

Prophylactic trimethoprim-sulfamethoxazole is recommended for all patients receiving alemtuzumab. 

The three monoclonal antibodies approved, noted in Table 23.1, in the last 7 years for treatment of patients with cancer include Alemtuzumab (Campath M) (Genzyme Corporation, Cambridge, MA, U.S.A.), Cetuzimab (Erbitux ) (ImClone Corporation, Branchburg, NJ, U.S.A.), and bevacizumab (Avastin ) (Genentech, South San Francisco, CA, U.S.A.). 

Examples of antibodies in the market include trastuzumab (anti-HER2 monoclonal antibody), rituximab, natalizumab (x4-integiin antibody), abciximab, infiximab (targets TNF-a in Crohn s disease and rheumatoid arthritis), alemtuzumab, adalimumab (TNF-a antibody for the treatment of rheumatoid arthritis) and efalizumab (anti-CDlla monoclonal antibody for the treatment of psoriasis)Rituximab is a mouse/human chimeric anti-CD20 monoclonal antibody used for the treatment of various l)unphoid malignancies. As CE)20 antigen is found on the surface of... 

Pharmacokinetics The pharmacokinetic profile of alemtuzumab was studied in a rising-dose trial in non-Hodgkin s lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Campath was administered once weekly for a maximum of 12 weeks. Following intravenous infusions over a range of doses, the maximum serum concentration (C ax) and the area under the curve (AUC) showed relative dose pro-... 

Similar to the result of FCGR polymorphism with rituximab therapy for CLL, Lin et al. (70) reported that the FCGR3A and FCGR2A polymorphism did not show any difference in response rate of relapsed CLL patients when treated with alemtuzumab (stepped-up dose schedule from 3 mg to 30 mg during the first week and then given at 30 mg three times a week for 12 weeks). 

In summary, the mechanism of monoclonal antibody activity for CLL might be different from that for lymphoma. Besides ADCC, other pathways such as caspase-dependent apoptosis or CDC are more likely to contribute to rituximab or alemtuzumab-induced clearance of CLL cells in vivo. 

Keating M, Coutre S, Rai K et al. Management guidelines for use of alemtuzumab in B-cell chronic lymphocytic leukemia. Clin Lymphoma 2004 4 220-227. 

Montillo M, Schinkoethe T, Elter T. Eradication of minimal residual disease with alemtuzumab in B-cell chronic lymphocytic leukemia (B-CLL) patients the need for a standard method of detection and the potential impact of bone marrow clearance on disease outcome. Cawcer/wvext 2005 23 488-496. 

NK cells, monocytes, macrophages, and a small population of granulocytes. Currently, alemtuzumab is approved for the treatment of -cell chronic lymphocytic leukemia in patients who have been treated with alkylating agents and have failed fludarabine therapy. Alemtuzumab appears to deplete leukemic and normal cells by direct antibody-dependent lysis. Patients receiving this antibody become lymphopenic and may also become neutropenic, anemic, and thrombocytopenic. As a result patients should be closely monitored for opportunistic infections and hematologic toxicity. 

Nine of 27 patients with multiple sclerosis developed antibodies against the thyrotropin receptor and carbima-zole-responsive autoimmune hyperthyroidism after a 5-day pulse of alemtuzumab, a finding that was not reported in patients treated for other disorders (18). 

Alemtuzumab is a humanized antibody that is directed against the cell-surface glycoprotein expressed on the surface of the normal and malignant B and T lymphocytes, and is indicated for the treatment of B-cell CLL [91]. 

Alemtuzumab (campath-lH) is a humanized monoclonal antibody specific for the CDw52 antigen, present on cell membranes of lymphocytes and monocytes. It has been used for treatment of patients with rheumatoid arthritis and vasculitis, is being investigated for the treatment of chronic lymphocytic leukemia, and has been used to deplete circulating lymphocytes in patients with multiple sclerosis (1). In 2001, alemtuzumab was approved in Europe for the treatment of chronic B cell lymphocytic leukemia that had been treated previously with alkylating agents and was refractory to fludarabine (2). It has also been used for induction of immunosuppression/tolerance in liver transplant recipients (3,4) and kidney/pancreas transplant recipients (5). 

Of 22 patients, median age 61 years, who had received a median of three previous types of therapy for mycosis fungoides or Sezary syndrome and were given alemtuzumab in increasing doses (from 3 to 30 mg three times a week for 12 weeks), 11 had no infectious complications, one had fatal pulmonary aspergillosis 2.5 months after the end of treatment, and another contracted fatal Mycobacterium pneumonia 10 months after the end of treatment (7). 

Marcos A, Eghtesad B, Fung JJ, Fontes P, Patel K, Devera M, Marsh W, Gayowski T, Demetris AJ, Gray EA, Flynn B, Zeevi A, Murase N, Starzl TE. Use of alemtuzumab and tacrolimus monotherapy for cadaveric liver transplantation with particular reference to hepatitis C virus Transplantation 2004 78(7) 966-71. 

Laurenti L, Piccioni P, Cattani P, Cingolani A, Efremov D, Chiusolo P, Tarnani M, Fadda G, Sica S, Leone G. Cytomegalovirus reactivation during alemtuzumab therapy for chronic lymphocytic leukemia incidence and treatment with oral ganciclovir. Haematologica 2004 89(10) 1248-52. 

Alemtuzumab (Campath) Anti-CD52 Ab - B-cell chronic lymphocytic leukemia - Preconditioning regimen for bone marrow and renal transplantation -HUS -Acute renal failure - Acute humoral rejection 98,99,101... 

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