You are using an outdated browser. We suggest you update your browser for a better experience. Click here for update.
Close this notification.
Skip to main content Skip to search
A - Drug Name

alemtuzumab

SYNONYM(S):   anti-CD52 monoclonal antibody; campath 1H

COMMON TRADE NAME(S):   MabCampath® (Sanofi Genzyme)

 
B - Mechanism of Action and Pharmacokinetics

Alemtuzumab is a monoclonal antibody that binds to the CD52 antigen on the surface of malignant lymphocytes and induces cell lysis. The CD52 antigen is present on the surface of essentially all B and T lymphocytes, most monocytes, macrophages, NK cells, and some granulocytes and normal bone marrow cells. Alemtuzumab was approved for use based on objective responses and progression-free survival. No data is available from randomized controlled trials regarding improved survival or quality of life.



Absorption
Oral: no
Distribution

Alemtuzumab displays non-linear elimination kinetics. Systemic clearance decreases with repeated administration due to decreased receptor-mediated clearance (i.e. loss of CD52 receptors in the periphery).

Cross blood brain barrier? No information found
PPB No information found
Metabolism
Active metabolites No information found
Inactive metabolites No information found
Elimination
Half-life 11 hours (range: 2-32 hours) after the first 30 mg dose and 6 days (range: 1-14 days) after the last 30 mg dose
 
C - Indications and Status
Health Canada Approvals:

  • Treatment of B cell chronic lymphocytic leukemia (B-CLL) in patients who have been treated with alkylating agents and who have failed fludarabine therapy.
  • Treatment of patients with previously untreated progressive B-CLL. The effectiveness is based on progression-free survival, complete response, and overall response rates. No current data available to demonstrate an increased overall survival.


 
D - Adverse Effects

Emetogenic Potential:  

Minimal

Extravasation Potential:   None

The following table contains adverse effects reported mainly in untreated patients.

ORGAN SITE SIDE EFFECT* (%) ONSET**
Cardiovascular Arrhythmia (7%) I  E
Arterial thromboembolism (<1%) I
Cardiotoxicity (rare) D
Hypertension (9%) I  E
Hypotension (14%) I
Venous thromboembolism (rare) E
Dermatological Local reactions (>1%) I
Rash (12%) I
Gastrointestinal Abdominal pain (3%) E
Anorexia, weight loss (2%) E
Diarrhea (1%) E
GI obstruction (rare) E
GI perforation (rare) E
Mucositis (<1%) E
Nausea, vomiting (13%) I  E
General Fatigue (6%) E
Hematological Disseminated intravascular coagulation (rare) E
Myelosuppression ± infection, bleeding (63%) (severe) E
Hepatobiliary Cholecystitis (rare) E
Pancreatitis (rare) E
Hypersensitivity Hypersensitivity (may be severe) I
Immune Autoimmune disorder (rare- hemolytic anemia, ITP, pure red cell aplasia, Goodpastures, Graves, etc.) E
Transfusion-associated GVHD E  D
Infection Immunosuppression/ atypical infection (53%) E
Metabolic / Endocrine Tumor lysis syndrome (1%) I
Musculoskeletal Musculoskeletal pain (2%) E
Neoplastic Secondary malignancy (and leukemia) D
Nervous System Anxiety (1%) E
Cognitive disturbance (2%) E
Dizziness (3%) I
Guillain-Barre syndrome E
Headache (7%) I
Neuropathy E
Syncope (1%) I  E
Tremor (3%) E
Vertigo (1%) E
Ophthalmic Conjunctivitis (<1%) E
Renal Nephrotoxicity (rare) E
Respiratory Cough, dyspnea (7%) I
Pleural effusion (rare) E
Pneumonitis (rare) E


* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.
Dose-limiting side effects are underlined.

** I = immediate (onset in hours to days)     E = early (days to weeks)
D = delayed (weeks to months)      L = late (months to years)

The most common adverse effects are infusion reactions, myelosuppression, infection, GI and CNS symptoms, fatigue and hypertension. The incidences of these effects are generally lower in previously untreated patients.

Alemtuzumab causes profound lymphopenia and results in a variety of opportunistic infections, including cytomegalovirus and PCP. Prophylaxis is strongly recommended during treatment and for 2 months after, or until CD4+ counts are >200cells/μL (counts may take up to a year to recover). Blood products administered prior to recovery from lymphopenia should be irradiated because of the potential for graft versus host disease in severely lymphopenic patients.

Severe, prolonged, and, in rare instances, fatal, myelosuppression has occurred, especially at doses above the recommended doses. If hematologic toxicity is severe, discontinue alemtuzumab. (See Dosing)

Autoimmune diseases, including Graves’ disease, hypothyroidism, Guillain-Barre and Goodpasture’s syndrome have been reported.

Infusion reactions are common, including hypotension, rigors, fever, shortness of breath, bronchospasm, chills, vomiting, and/or rash. Acute infusion-related reactions were most common during the first week of therapy. Antihistamines, acetaminophen, antiemetics, meperidine, and corticosteroids, as well as incremental dose escalation, should be used to prevent or ameliorate infusion-related reactions. Supportive care should be available. Anti-human antibodies are seen in 8% of patients. Patients may cross-react to other monoclonal antibodies.

There have been reports of fatal progressive multiforcal leukoencephalopathy (PML) in B-CLL patients treated with or without alemtuzumab, Alemtuzumab should be held at first signs or symptoms suggestive of PMLand patients suspected of having PML should be investigated appropriately.

There is a risk of serious infusion-related cardiac complications, including myocardial infarction and cardiac arrhythmias. Careful monitoring is recommended and resuscitation facilities should be available. Alemtuzumab should only be administered to patients with pre-existing cardiac disease if the benefits outweigh the risks.

 
E - Dosing

Refer to protocol by which patient is being treated. Alemtuzumab should be escalated rapidly (usually over 3-7 days) based on tolerance, to the 3 times/week maintenance dose. If therapy is missed for seven or more days, alemtuzumab dose must be re-escalated as below.

Single doses of alemtuzumab greater than 30mg or cumulative weekly doses of greater than 90mg should never be administered.

 


Adults:

Premedication/prophylaxis:

1. Diphenhydramine 50mg and acetaminophen 650mg 30 minutes before infusion

2. Trimethoprim/sulfamethoxazole DS twice daily three times per week and famciclovir (or equivalent) 250mg bid during treatment and for 2 months after or until CD4+ count is ≥ 200cells/μL

3. Allopurinol and hydration to reduce the risk of tumour lysis syndrome are recommended.

4. Irradiated blood products should be used


Administration and Escalation
 
Step
 
Dose
Next Steps
1
Initial dose / restart after ≥ 7days hold
3mg Daily as a 2-hour IV infusion
When infusion toxicity ≤ G2, then proceed to step #2
 
2
 
10mg Daily as a 2-hour IV infusion
When infusion toxicity ≤ G2, then proceed to step #3
 
3
maintenance
30mg 3 x week as a 2-hour IV infusion (Mon-Wed-Fri) for ≤ 12 weeks
 



Dosage with Toxicity:

Dose modification for toxicity:

Toxicity (grade or 109)
1st Occurrence
2nd Occurrence
3rd Occurrence
ANC < 0.25 and/or
platelet ≤ 25
Hold, restart at same dose when ANC ≥ 0.5 and platelets  ≥ 50
Hold, restart at 10mg when ANC ≥ 0.5 and platelets ≥ 50
Discontinue
If baseline ANC ≤ 0.25, and/or platelet ≤ 25 and ↓ 50%
Hold, restart at same dose when ≥ baseline
Hold, restart at 10mg when ≥ baseline
Discontinue
≥ Grade 3 non-hematologic toxicity, including serious infections and CMV viremia
Hold until ≤ grade 2. Consider dose modification 
 
 
≥ Grade 3 infusion reaction
Hold.  Add meperidine and hydrocortisone as pre-medications.
 
 
Autoimmune disorders
Discontinue
 
 
PML, autoimmune anemia or thrombocytopenia
Discontinue
 
 
If delay between dosing is ≥ 7 days, must re-escalate starting from 3mg
Do not modify dose for lymphopenia



Dosage with Hepatic Impairment:

No information found.

Dosage with Renal Impairment:

No information found.

Dosage in the elderly:

Limited experience, no dose modifications appear required.

Children:

The safety and efficacy of alemtuzumab in children have not been studied.

 
F - Administration Guidelines

  • See the Product Monograph for full details of preparation and administration.
  • Full resuscitation facilities and experienced personnel should be available.
  • Do not administer as an intravenous push or bolus. Although not approved by Health Canada, alemtuzumab has been given subcutaneously in phase II studies
  • Mix in 100mL IV bag (5% Dextrose or Normal Saline). Gently invert the bag to mix the solution. Infuse the admixture over 2 hours.
  • Other drug substances should not be added or simultaneously infused through the same intravenous line.


 
G - Special Precautions
Other:

Alemtuzumab is contraindicated in patients with active infections, underlying immunodeficiency (e.g., seropositive for HIV), history of progressive multifocal leukoencephalopathy (PML), known Type I hypersensitivity or anaphylactic reactions to alemtuzumab or any components of MabCampath, or in patients with active secondary malignancies. Gradual escalation to the recommended maintenance dose is required at the initiation of therapy and after interruption of therapy for more than 7 days. Alemtuzumab can result in serious and even fatal infusion reactions. Monitor patients closely during infusions and discontinue alemtuzumab if indicated.

Serious, and in rare instances, fatal pancytopenia, and autoimmune idiopathic thrombocytopenia or hemolytic anemia have occurred. Single doses greater than 30mg or cumulative doses of more than 90mg per week should not be administered, as they are associated with a higher incidence of pancytopenia. Serious and fatal bacterial, fungal, viral, and protozoal infections have been reported. Anti-viral and anti-Pneumocystis carinii pneumonia prophylaxis are strongly recommended. All blood products should be irradiated. Live vaccines should not be administered. Use with caution in patients with pre-existing cardiac disease.

It is not known whether alemtuzumab is carcinogenic or mutagenic but is likely to cause fetal harm and to impair fertility. IgG can cross the placental barrier; alemtuzumab should be given to pregnant women only if the benefits outweigh the risks to the mother and fetus. Women of childbearing potential and men of reproductive potential should use effective contraceptive methods during treatment and for a minimum of six months following alemtuzumab therapy. IgG is secreted in human milk; therefore, breastfeeding should be discontinued for at least three months after cessation of therapy.

 
H - Interactions

No formal drug interaction studies have been performed. An immune response to alemtuzumab may interfere with subsequent diagnostic serum tests that utilize antibodies.

AGENT EFFECT MECHANISM MANAGEMENT
Vaccines May impair response to vaccinations Immunosuppression Avoid
Anticoagulants, NSAIDs, platelet inhibitors, thrombolytic agents ↑ risk of bleeding Additive Caution; monitor
Antihypertensives ↑ hypotension Additive hypotensive effect with infusion reactions Caution; monitor
 
I - Recommended Clinical Monitoring

Recommended Clinical Monitoring

Monitor Type Monitor Frequency
CBC and platelets Weekly and as needed
Clinical toxicity assessment for infusion reactions, respiratory and cardiac events, auto-immune disorders, bleeding and infection.

Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

Suggested Clinical Monitoring

Monitor Type Monitor Frequency
Consider CMV monitoring.
CD4+ counts should be assessed after treatment until recovery to ≥ 200 cells/μL
 
K - References

Product Monograph: MabCampath® (alemtuzumab). Genzyme Canada Inc., March 22, 2010.

Lundin J, Kimby E, Bjorkholm M, et al. Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath-1H) as first-line treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL). Blood 2002;100:768-773.

Stilgenbauer S, Zenz T, Winkler D, et al. Subcutaneous alemtuzumab in fludarabine-refractory chronic lymphocytic leukemia: clinical results and prognostic marker analyses from the CLL2H study of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2009;27(24): 3994-4001.


 
L - Disclaimer

Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.

The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.

Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.

While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.

CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.