Alemtuzumab
Gale Encyclopedia of Cancer:
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Alemtuzumab
Key Terms: Alkylating agent, Antibody, Autoimmune, Humanization, Monoclonal.
Definition
Alemtuzumab is sold as Campath in the United States. Alemtuzumab is a humanized monoclonal antibody that selectively binds to CD52 (a protein found on the surface of normal and malignant B and T cells) that is used to reduce the numbers of circulating malignant cells of patients who have B-cell chronic lymphocytic leukemia (B-CLL).
Purpose
Alemtuzumab is a monoclonal antibody used to treat B-CLL, one of the most prevalent forms of adult chronic leukemia. It specifically binds CD52, a protein found on the surface of essentially all B and T cells of the immune system. By binding the CD52 protein on the malignant B cells, the antibody targets it for removal from the circulation. Scientists believe that alemtuzumab triggers antibody-mediated lysis of the B cells, a method that the immune system uses to eliminate foreign cells.
Alemtuzumab has been approved by the FDA for treatment of refractory B-CLL. For a patient's disease to be classified as refractory, both alkylating agents and fludarabine treatment must have been tried and failed. Thus, this drug gives patients who have tried all approved treatments for B-CLL another option. As most patients with B-CLL are in stage III or IV by the time both alkylating agents and fludarabine have been tried, the experience with alemtuzumab treatment are primarily with those stages of the disease. In clinical trials, about 30% of patients had a partial response to the drug, with 2% of these being complete responses.
This antibody has been tested with limited success in the treatment of non-Hodgkin's lymphoma (NHL) and for the preparation of patients with various immune cell malignancies for bone marrow transplantation. There is also a clinical trial ongoing to test the ability of this antibody to prevent rejection in kidney transplantation.
Description
Alemtuzumab is produced in the laboratory using genetically engineered single clones of B cells. Like all antibodies, it is a Y-shaped molecule can bind one particular substance, the antigen for that monoclonal antibody. For alemtuzumab, the antigen is CD52, a protein found on the surface of normal and malignant B and T cells as well as other cells of the immune and male reproductive systems. Alemtuzumab is a humanized antibody, meaning that the regions that bind CD52, located on the tips of the Y branches, are derived from rat antibodies, but the rest of the antibody is human sequence. The presence of the human sequences helps to reduce the immune response by the patient against the antibody itself, a problem seen when complete mouse antibodies are used for cancer therapies. The human sequences also help to ensure that the various cell-destroying mechanisms of the human immune system are properly triggered with binding of the antibody.
Alemtuzumab was approved in May of 2001 for the treatment of refractory B-CLL. It is approved for use alone but clinical trials have tested the ability of the antibody to be used in combination with the purine analogs pentostatin, fludarabine, and cladribine, and rituximab, a monoclonal antibody specific for the CD20 antigen, another protein found on the surface of B cells.
Recommended Dosage
This antibody should be administered in a gradually escalating pattern at the start of treatment and any time administration is interrupted for 7 or more days. The recommended beginning dosage for B-CLL patients is a daily dose of 3 mg of Campath administered as a 2-hour IV infusion. Once this amount is tolerated, the dose is increased to 10 mg per day. After tolerating this dose, it can be increased to 30 mg, administered three days a week. Acetominophen and diphenhydramine hydrochoride are given thirty to sixty minutes before the infusion to help reduce side effects.
Additionally, patients generally receive anti-infective medication before treatment to help minimize the serious opportunistic infections that can result from this treatment. Specifically, trimethoprim/sulfamethoxazole (to prevent bacterial infections) and famciclovir (to prevent viral infections) were used during the clinical trial to decrease infections, although they were not eliminated.
Precautions
Blood studies should be done on a weekly basis while patients are receiving the alemtuzumab treatment. Vaccination during the treatment session is not recommended, given the T cell depletion that occurs during treatment. Furthermore, given that antibodies like alumtuzumab can pass through the placenta to the developing fetus and in breast milk, use during pregnancy and breastfeeding is not recommended unless clearly needed.
Side Effects
A severe side effect of alemtuzumab treatment is the possible depletion of one or more types of blood cells. Because CD52 is expressed on a patient's normal B and T cells, as well as on the surface of the abnormal B cells, the treatment eliminates both normal and cancerous cells. The treatment also seems to trigger autoimmune reactions against various other blood cells. This results in severe reduction of the many circulating blood cells including red blood cells (anemia), white blood cells (neutropenia), and clotting cells (thrombocytopenia). These conditions are treated with blood transfusions. The great majority of patients treated exhibit some type of blood cell depletion.
A second serious side effect of this drug is the prevalence of opportunistic infections that occurs during the treatment. Serious, and sometimes fatal bacterial, viral, fungal, and protozoan infections have been reported. Treatments to prevent pneumonia and herpes infections reduce, but do not eliminate these infections.
The majority of other side effects occur after or during the first infusion of the drug. Some common side effects of this drug include fever and chills, nausea and vomiting, diarrhea, shortness of breath, skin rash, and unusual fatigue. This drug can also cause low blood pressure (hypotension).
In patients with high tumor burden (a large number of circulating malignant B cells) this drug can cause a side effect called tumor lysis syndrome. Thought to be due to the release of the lysed cells' contents into the blood stream, it can cause a misbalance of urea, uric acid, phosphate, potassium, and calcium in the urine and blood. Patients at risk for this side effect must keep hydrated and can be given allopurinol before infusion.
Interactions
There have been no formal drug interaction studies done for alemtuzumab.
—Michelle Johnson, M.S., J.D.
Drug Info:
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Alemtuzumab
Brand names: Campath®
- Espa�ol:
- Alemtuzumab Solución para inyección
Alemtuzumab Solution for injection
What is this medicine?
ALEMTUZUMAB (AL em TOOZ oo mab) is a chemotherapy drug. It is used to treat B cell chronic lymphocytic leukemia.
This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.
What should I tell my health care provider before I take this medicine?
They need to know if you have any of these conditions:
•any active infection
•cold sores
•dental disease
•heart disease
•human immunodeficiency virus (HIV) or AIDS
•immune system problems
•an unusual or allergic reaction to alemtuzumab, hamster proteins, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding
How should I use this medicine?
The medicine is for infusion into a vein. It is given by a health care professional in a hospital or clinic setting. You may receive acetaminophen (Tylenol) and diphenhydramine (Benadryl) before your infusion to help decrease side effects related to the medicine. Your doctor may also give you antibiotics to help prevent infections.
Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.
Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.
What may interact with this medicine?
•medicines for high blood pressure
•vaccines
This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.
What should I watch for while using this medicine?
Your condition will be monitored carefully while you are receiving this medicine.
Visit your doctor or health care professional for regular checks on your progress. You will need frequent blood checks. The side effects of the medicine can continue after you finish your treatment. Promptly report any side effects.
This drug may make you feel generally unwell. This is not uncommon, as chemotherapy can affect healthy cells as well as cancer cells. Report any side effects. Continue your course of treatment even though you feel ill unless your doctor tells you to stop.
Call your doctor or health care professional for advice if you get a fever, chills or sore throat, or other symptoms of a cold or flu. Do not treat yourself. This drug decreases your body's ability to fight infections. Try to avoid being around people who are sick.
This medicine may increase your risk to bruise or bleed. Call your doctor or health care professional if you notice any unusual bleeding.
Be careful brushing and flossing your teeth or using a toothpick because you may get an infection or bleed more easily. If you have any dental work done, tell your dentist you are receiving this medicine.
Avoid taking products that contain aspirin, acetaminophen, ibuprofen, naproxen, or ketoprofen unless instructed by your doctor. These medicines may hide a fever.
Do not become pregnant while taking this medicine. Women should inform their doctor if they wish to become pregnant or think they might be pregnant. There is a potential for serious side effects to an unborn child. Men should inform their doctors if they wish to father a child. Men and women need to use effective contraceptive methods during treatment and for at least 6 months after stopping this medicine. Talk to your health care professional or pharmacist for more information. Do not breast-feed an infant while taking this medicine.
What side effects may I notice from receiving this medicine?
Side effects that you should report to your doctor or health care professional as soon as possible:
•allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
•chest pain
•diarrhea
•difficulty breathing, wheezing
•dizziness or fainting
•palpitations
•shortness of breath
•signs of infection like fever or chills, cough, sore throat, pain or difficulty passing urine
•unusual bleeding or bruising
•unusually weak or tired
•vomiting
Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
•constipation
•diarrhea
•fatigue
•headache
•insomnia
•nausea
This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Where should I keep my medicine?
This drug is given in a hospital or clinic and will not be stored at home.
Last updated: 7/1/2002
Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.
Oxford A-Z of Medicinal Drugs:
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alemtuzumab
A monoclonal antibody that specifically destroys B lymphocytes (a type of white blood cell). It is used in the treatment of chronic lymphocytic leukaemia (see cancer) when conventional therapy with fludarabine is not appropriate. Alemtuzumab can cause allergic reactions during infusion (see rituximab) and can predispose to infections. Because of this, an analgesic, a corticosteroid, and an antibiotic should be taken before treatment starts. Alemtuzumab is given under expert supervision by slow intravenous infusion and is available on prescription only.
Side effects and precautions:
see rituximab.
Proprietary preparation:
MabCampeth.
| aldesleukin, alclometasone dipropionate, agonist | |
| alendronic acid, alfacalcidol, alfentanil |
Wikipedia on Answers.com:
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Alemtuzumab
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|
|---|---|
| Monoclonal antibody | |
| Type | Whole antibody |
| Source | Humanized (from rat) |
| Target | CD52 |
| Clinical data | |
| Trade names | Campath |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a608053 |
| Pregnancy cat. | B2 (AU) |
| Legal status | ? |
| Pharmacokinetic data | |
| Half-life | ~288 hrs |
| Identifiers | |
| CAS number | 216503-57-0  |
| ATC code | L01XC04 |
| DrugBank | DB00087 |
| UNII | 3A189DH42V |
| ChEMBL | CHEMBL1201587  |
| Chemical data | |
| Formula | C6468H10066N1732O2005S40 |
| Mol. mass | 145453.8 g/mol |
 (what is this?) (verify) |
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Alemtuzumab (marketed as Campath, MabCampath or Campath-1H and currently under further development as Lemtrada) is a monoclonal antibody used in the treatment of chronic lymphocytic leukemia (CLL), cutaneous T-cell lymphoma (CTCL) and T-cell lymphoma. It is also used in some conditioning regimens for bone marrow transplantation, kidney transplantation and Islet cell transplantation.
Alemtuzumab targets CD52, a protein present on the surface of mature lymphocytes, but not on the stem cells from which these lymphocytes are derived.
Alemtuzumab is used as second-line therapy for CLL. It was approved by the US Food and Drug Administration for CLL patients who have been treated with alkylating agents and who have failed fludarabine therapy. It has been approved by Health Canada for the same indication, and additionally for CLL patients who have not had any previous therapies.
It is also used under clinical trial protocols for treatment of some autoimmune diseases, such as multiple sclerosis, in which it shows promise. [1] [2]
A significant complication of therapy with alemtuzumab is that it significantly increases the risk for opportunistic infections, in particular, reactivation of cytomegalovirus.
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Contents
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Description
Alemtuzumab (Campath-1H) is a recombinant DNA-derived humanized monoclonal antibody that is directed against the 21–28 kDa cell surface glycoprotein, CD52.
Indications and use
Alemtuzumab is indicated for the treatment of B-cell chronic lymphocytic leukemia (B-CLL) in patients who have been treated with alkylating agents and who have failed fludarabine therapy. It is an unconjugated antibody, thought to work via the activation of antibody-dependent cell-mediated cytotoxicity(ADCC).[3]
Research or off-label use
Multiple sclerosis
In 2008 early tests at Cambridge University suggest that alemtuzumab might be useful in treating and even reversing the effects of multiple sclerosis.[4] Promising results were reported in 2011 from a phase III trial against Rebif. A combination trial with Copaxone is being considered, and is expected to work synergistically. [2]
Graft-versus-host disease
A 2009 study of alemtuzumab in 20 patients with severe steroid-resistant acute intestinal graft-versus-host disease after allogeneic hematopoietic cell transplantation (HCT) demonstrated improvement. Overall response rate was 70%, with complete response in 35%. In this study, the median survival was 280 days. Important complications following this treatment included cytomegalovirus reactivation, bacterial infection, and invasive aspergillosis infection.[5]
Contraindications and precautions
Alemtuzumab is contraindicated in patients who have active systemic infections, underlying immunodeficiency (e.g., seropositive for HIV), or known Type I hypersensitivity or anaphylactic reactions to Campath or to any one of its components.
Adverse reactions
Alemtuzumab has been associated with infusion-related events including hypotension, rigors, fever, shortness of breath, bronchospasm, chills, and/or rash. In post-marketing reports, the following serious infusion-related events were reported: syncope, pulmonary infiltrates, ARDS, respiratory arrest, cardiac arrhythmias, myocardial infarction and cardiac arrest. The cardiac adverse events have resulted in death in some cases.[citation needed]
It is also possible that perturbation of suppressor T cell populations by Campath-1H may precipitate autoimmune disease.[citation needed]
History
The origins of alemtuzumab date back to Campath-1 which was derived from the rat antibodies raised against human lymphocyte proteins by Herman Waldmann and colleagues.[6] The name "Campath" derives from the pathology department of Cambridge University.
Initially, Campath-1 was not ideal for therapy because patients could, in theory, react against the foreign rat protein determinants of the antibody. To circumvent this problem, Greg Winter and his colleagues humanised Campath-1, by extracting the hypervariable loops that had specificity for CD52 and grafting them onto a human antibody framework. This became known as Campath-1H and serves as the basis for alemtuzumab.[7]
Campath is marketed in the United States and Canada by Genzyme.
References
- ^ "Drug may reverse MS brain damage". 22 Oct 2008. http://news.bbc.co.uk/1/hi/health/7680641.stm.
- ^ a b "Sanofi and Genzyme Report New Positive Data from First Phase III Study with MS Drug". 24 Oct 2011. http://www.genengnews.com/gen-news-highlights/sanofi-and-genzyme-report-new-positive-data-from-first-phase-iii-study-with-ms-drug/81245853/.
- ^ http://www.campath.com/hcp/AboutCampath.html
- ^ Drug reboots immune system to reverse MS, Andy Coghlan, New Scientist News Service, October 23, 2008.
- ^ Successful treatment of severe acute intestinal graft-versus-host resistant to systemic and topical steroids with alemtuzumab., Schnitzler M, Biol Blood Marrow Transplant. 2009 Aug;15(8):910-8.
- ^ Hale G, Bright S, Chumbley G, Hoang T, Metcalf D, Munro AJ, Waldmann H. Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement. Blood 1983;62:873-82. PMID 6349718.
- ^ Riechmann L, Clark M, Waldmann H, Winter G. Reshaping human antibodies for therapy. Nature 1988;332:323-7. doi:10.1038/332323a0 PMID 3127726.
External links
- Full Prescribing Information
- Mike Clark's Campath story
- From laboratory to clinic: the story of CAMPATH-1 (Geoff Hale and Herman Waldmann)
- Fact Sheet about Alemtuzamab (Campath)
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Copyrights:
Gale Encyclopedia of Cancer
Gale Encyclopedia of Cancer. Copyright © 2006 by The Gale Group, Inc. All rights reserved.
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Oxford A-Z of Medicinal Drugs
Market University Press. © 2000, 2003, 2010 An A-Z of Medicinal Drugs. All rights reserved.
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