Alemtuzumab, a recombinant DNA-derived humanized anti-CD52 monoclonal antibody, is an antineoplastic agent.1
Alemtuzumab is used as a single agent for the treatment of B-cell chronic lymphocytic leukemia (B-CLL).1 The drug has been used in both previously untreated and previously treated patients (i.e., patients who have been treated with alkylating agents and who have not responded adequately to fludarabine therapy).1, 6, 8
As of September 2012, alemtuzumab (Campath®) no longer is commercially available in the US, but may be obtained through the Campath® Distribution Program for patients who require continued access to the drug.37 Additional information about the Campath® Distribution program is available at 877-422-6728.37
Use of alemtuzumab in previously untreated patients with B-CLL is based on the results of an open-label, randomized, active-controlled trial involving 297 patients who were mostly male (72%) and Caucasian (99%) with a median age of 60 years and a WHO performance status of 0-1 (96%).1, 31 About one-third of the patients had Rai stage III or IV disease and 23% of the patients had a maximum lymph node diameter of 5 cm or greater.1, 31 Patients received either alemtuzumab 30 mg IV 3 times per week for up to 12 weeks or chlorambucil 40 mg/m2 orally once every 28 days for up to 12 cycles.1, 31 Alemtuzumab was escalated from a daily dose of 3 to 10 mg as tolerated and then administered on the 30 mg 3 times per week schedule for a total duration of therapy up to 12 weeks (including the dose escalation phase).1, 31 Patients receiving alemtuzumab as first-line therapy for B-CLL had prolonged median progression-free survival (14.6 versus 11.7 months) compared with those receiving chlorambucil.1, 31 Higher rates of overall response (83 versus 55%) and complete response (24 versus 2%) were observed in patients receiving alemtuzumab versus chlorambucil for progressive B-CLL.1, 31 Grade 3 or 4 neutropenia, infusion-related reactions, and cytomegalovirus (CMV) infections occurred more frequently in patients receiving alemtuzumab whereas nausea and vomiting occurred more frequently in patients receiving chlorambucil.31
In a noncomparative phase 2 study evaluating subcutaneous† alemtuzumab (maintenance dosage of 30 mg 3 times weekly for up to 18 weeks following escalation of the dosage to that level) as first-line therapy in 41 patients with B-CLL, the overall response rate was 87% (19% complete responses, 68% partial responses).34 About 71% of the evaluable patients in this study had Rai stage III or IV disease, 18% of the patients had a maximum lymph node diameter exceeding 5 cm, and 53% were older than 65 years of age.34
Higher response rates, longer progression-free survival, and similar overall survival have been observed in patients receiving fludarabine rather than chlorambucil as initial therapy for CLL.33
Use of alemtuzumab in previously treated patients with B-CLL is based principally on the results of 3 multicenter, open-label, noncomparative studies in 149 patients with B-CLL.1 The first 2 studies enrolled a total of 56 patients who had been previously treated with alkylating agents, fludarabine, or other antineoplastic agents. 10, 20 The third study enrolled 93 patients who had been previously treated with alkylating agents and in whom fludarabine therapy failed (i.e., lack of objective partial or complete response to at least one fludarabine-containing regimen, progression of disease during treatment with fludarabine, or relapse within 6 months of discontinuing fludarabine).4 All patients received alemtuzumab 30 mg (dosage escalated gradually to that level) as an IV infusion 3 times weekly for 4-12 weeks.1, 4 In the third study, patients also received prophylaxis against Pneumocystis jiroveci (formerly Pneumocystis carinii ) and herpes virus infections during alemtuzumab therapy and for at least 2 months after the last dose of alemtuzumab; 4 anti-infective prophylaxis was optional in the first 2 studies. 10, 20 The overall response rates for the 3 clinical studies were 21-33%, with 0-2% of patients exhibiting complete responses and 21-31% exhibiting partial responses.1
In a noncomparative, phase 2 study evaluating subcutaneous† alemtuzumab (subcutaneous maintenance dosage of 30 mg 3 times weekly for up to 12 weeks following either IV or subcutaneous escalation of the dosage to that level) in 103 patients with fludarabine-refractory B-CLL, the overall response rate was 34%; median overall and progression-free survival times were 19.1 and 7.7 months, respectively.35
Alemtuzumab has been investigated as an active agent for use in the treatment of T-cell prolymphocytic leukemia (T-PLL)†.6 Among patients receiving alemtuzumab for T-PLL, most of whom had received previous treatment, response rates of 73% and 76% were reported in 2 small uncontrolled studies,25, 26 and a response rate of 51% was reported in a retrospective review of 76 patients.27 A high response rate has been reported in 11 patients receiving alemtuzumab as initial therapy for T-PLL.28
In limited numbers of patients, alemtuzumab has shown activity, but also substantial toxicity, such as hematologic toxicity and serious infectious complications, in previously treated non-Hodgkin lymphoma†, including refractory peripheral T-cell lymphoma,13 advanced cutaneous T-cell lymphoma (mycosis fungoides/Sézary syndrome),14, 15, 18 and advanced low-grade non-Hodgkin lymphoma.16, 17, 18, 19 The use of alemtuzumab as treatment or as a component of a conditioning regimen prior to stem cell transplantation for non-Hodgkin lymphoma is being investigated.8, 11
Reconstitution and Administration
Alemtuzumab is administered by IV infusion (after dilution) over 2 hours.1 The drug should not be administered by rapid IV injection, such as IV push or bolus .1 Alemtuzumab also may be administered by subcutaneous injection†.34, 35, 36
Alemtuzumab injection should be stored at 2-8°C and protected from light; solutions that have been frozen should be thawed at 2-8°C.1, 5 Alemtuzumab injection should be inspected visually for particulate matter and discoloration prior to dilution and administration;1 the drug should be discarded if the injection or diluted solution is discolored or contains a precipitate.1 The injection should not be shaken.1 The manufacturer states that strict aseptic technique must be observed in preparing and administering alemtuzumab solutions since the injection contains no preservative.1 The vial is intended for single use only; any unused portion of the drug should be discarded after withdrawal of the dose.1
For IV infusion, the appropriate dose of alemtuzumab should be withdrawn into a syringe.1 For preparation of the 3-mg dose, 0.1 mL of alemtuzumab should be withdrawn from the vial using a 1-mL syringe calibrated in increments of 0.01 mL.1 For preparation of the 10-mg dose, 0.33 mL of alemtuzumab should be withdrawn from the vial using a 1-mL syringe calibrated in increments of 0.01 mL.1 For preparation of the 30-mg dose, 1 mL of alemtuzumab should be withdrawn from the vial using either a 1-mL syringe or a 3-mL syringe calibrated in increments of 0.1 mL.1 Alemtuzumab should be diluted in 100 mL of 0.9% sodium chloride or 5% dextrose injection; the bag should be inverted gently to mix the solution.1 The diluted drug should be protected from light and may be stored at room temperature (15-30°C) or under refrigeration (2-8°C) for up to 8 hours.1, 5 Alemtuzumab should not be admixed with any other drug; nor should any other drug be administered simultaneously in the same IV line with alemtuzumab infusion.1
The manufacturer states that alemtuzumab solution is compatible with polyvinylchloride (PVC) bags and PVC or polyethylene-lined PVC administration sets.1
Alemtuzumab therapy must be initiated at low doses and increased gradually as tolerated to the maximum recommended single dose of 30 mg administered 3 times weekly on alternate days (i.e., Monday, Wednesday, Friday) for the treatment of B-cell chronic lymphocytic leukemia (B-CLL).1 Gradual titration to the recommended dosage also is required in patients who have discontinued therapy for 7 or more days.1
The manufacturer's recommended dose escalation strategy is as follows. Administer an initial dosage of 3 mg daily by IV infusion.1, 4 If this dosage is well tolerated (e.g., infusion-related reactions are grade 2 or lower), the dosage should then be increased to 10 mg daily until infusion-related reactions are grade 2 or lower.1, 4 If this dosage is well tolerated, the recommended maintenance dosage of 30 mg administered 3 times weekly on alternate days (i.e., Monday, Wednesday, Friday) may be administered.1, 4 In most patients, escalation to a dose of 30 mg can be accomplished in 3-7 days.1 The total duration of therapy, including initial dose escalation, is 12 weeks.1 The manufacturer warns that single doses exceeding 30 mg or cumulative weekly doses exceeding 90 mg increase the incidence of pancytopenia.1
Some experts state that alemtuzumab may be administered by subcutaneous injection† at the same maintenance dosage that is used for IV administration (30 mg 3 times weekly on alternate days1, 4 ) for at least 12 weeks (36 doses) in the treatment of B-CLL.36 In several studies, dosage of the drug was escalated from an initial dose of 3 mg to this maintenance dosage.34, 35, 36 In one study evaluating subcutaneous alemtuzumab as first-line therapy for B-CLL, escalation to a maintenance dosage of 30 mg 3 times weekly was accomplished by administering an initial dosage of 3 mg daily followed by increases in dosage to 10 mg on day 3 and then to 30 mg on day 5, provided each dose level was tolerated.34 In another study in patients with fludarabine-refractory B-CLL, escalation to a maintenance dosage of 30 mg 3 times weekly was accomplished by administering an initial dose of 3 mg on day 1, followed by 10 mg on day 2, and then 30 mg on day 3, provided each dose level was tolerated.35 If symptomatic local reactions occur during dosage escalation, experts state that the escalation period may be prolonged to up to 2 weeks.34, 36 In these 2 studies of subcutaneous alemtuzumab therapy, the maintenance dosage of alemtuzumab was administered for up to 18 weeks or up to 12 weeks, respectively.34, 35 In the study evaluating subcutaneous alemtuzumab as first-line therapy for B-CLL, if treatment was interrupted for longer than 7 days, therapy was reinitiated at a lower dosage (i.e., 3 or 10 mg).34
Local reactions, including erythema, edema, pruritus, and pain, have been reported, generally during the first 1-2 weeks of therapy, in patients receiving subcutaneous† therapy with alemtuzumab.34, 35, 36 Some experts state that if symptomatic local reactions occur during dosage escalation, the escalation period may be prolonged to up to 2 weeks.34, 36 Some data suggest that injection site reactions to subcutaneous alemtuzumab administration may be more common in patients receiving the drug as first-line therapy for B-CLL than in those with previously treated disease.34, 35, 36
Dosage Modification for Toxicity and Contraindications for Continued Therapy
Alemtuzumab doses should be withheld during serious adverse reactions until resolution of the toxicity.1 Discontinuance of alemtuzumab therapy may be necessary.1
Dosage of alemtuzumab should be modified based on severe cytopenias (except lymphopenia).1 No dosage modifications are recommended for lymphopenia.1
For patients exhibiting a first occurrence of myelosuppression (i.e., absolute neutrophil counts [ANC] of less than 250/mm3 and/or platelet counts of 25,000/mm3 or less), the manufacturer recommends that subsequent doses of the drug be withheld until ANC reaches or exceeds 500/mm3 and platelet counts reach or exceed 50,000/mm3.1 Alemtuzumab therapy may then be resumed at the maintenance dosage (i.e., 30 mg 3 times weekly).1 If 7 or more days have elapsed since discontinuance of alemtuzumab therapy, the drug should be reinitiated at 3 mg daily and titrated to the maintenance dosage of 30 mg 3 times weekly using the manufacturer's recommended dosing schedule.1
Following a second occurrence of myelosuppression, alemtuzumab therapy should be withheld until neutrophil and platelet counts return to acceptable levels (ANC of 500/mm3 or greater and platelet count of 50,000/mm3 or greater).1 Alemtuzumab may then be reinitiated at 10 mg 3 times weekly;5 higher dosages are not recommended in these patients.1, 5 If 7 or more days have elapsed since discontinuance of alemtuzumab therapy, the drug should be reinitiated at 3 mg daily and increased to a maximum maintenance dosage of 10 mg 3 times weekly.1, 5
Following a third occurrence of myelosuppression, the manufacturer states that alemtuzumab therapy should be discontinued permanently .1
For patients initiating alemtuzumab therapy with a baseline ANC of 250/mm3 or less and/or platelet counts of 25,000/mm3 or less in whom ANC and/or platelet counts decrease by 50% or greater from baseline values, alemtuzumab therapy should be withheld temporarily and resumed at the maintenance dosage (i.e., 30 mg 3 times weekly)5 only when neutrophil and/or platelet counts return to baseline values.1 If 7 or more days have elapsed since discontinuance of alemtuzumab therapy, the drug should be reinitiated at 3 mg daily and titrated to the maintenance dosage of 30 mg 3 times weekly using the manufacturer's recommended dosing schedule.1, 5
Following a second occurrence of a decrease of 50% or greater from baseline values in patients initiating alemtuzumab therapy with a baseline ANC of 250/mm3 or less and/or platelet counts of 25,000/mm3 or less, alemtuzumab therapy should be withheld until neutrophil and/or platelet counts return to baseline values.1 Alemtuzumab may then be reinitiated at 10 mg 3 times weekly.1 If 7 or more days have elapsed since discontinuance of alemtuzumab therapy, the drug should be reinitiated at 3 mg daily and increased to a maximum maintenance dosage of 10 mg 3 times weekly.1
Following a third occurrence of a decrease of 50% or greater from baseline values in patients initiating alemtuzumab therapy with a baseline ANC of 250/mm3 or less and/or platelet counts of 25,000/mm3 or less, alemtuzumab therapy should be discontinued permanently .1
Alemtuzumab should be withheld in patients experiencing grade 3 or 4 infusion reactions.1 Medical management (e.g., glucocorticoids, epinephrine, meperidine) should be initiated as clinically indicated.1
If a serious infection occurs, alemtuzumab should be discontinued temporarily; therapy may be reinitiated following resolution of the infection.1
Alemtuzumab should be withheld during antiviral therapy for CMV infection or confirmed CMV viremia (defined as positive for CMV according to the polymerase chain reaction [PCR] in 2 or more consecutive samples obtained at least 1 week apart) and anti-infective therapy (ganciclovir or equivalent) should be initiated.1
No special population dosage recommendations at this time.1
Severe, including fatal, pancytopenia/marrow hypoplasia, autoimmune idiopathic thrombocytopenia, and autoimmune hemolytic anemia can occur in patients receiving alemtuzumab.1, 5 A boxed warning regarding this risk has been included in the prescribing information for alemtuzumab (Campath®).1 Hemolytic anemia, pure red cell aplasia, and bone marrow aplasia and hypoplasia have occurred in patients receiving the recommended dosage of alemtuzumab.1 Single doses of alemtuzumab exceeding 30 mg or cumulative weekly doses exceeding 90 mg increase the incidence of pancytopenia.1
Among treatment-naive patients receiving alemtuzumab for B-cell chronic lymphocytic leukemia (B-CLL) in a randomized trial, grade 3 or 4 lymphopenia occurred in 97% of patients.1 Neutropenia occurred in 77% (grade 3 or 4 in 42%) of patients with a median time to onset of 31 days and a median duration of 37 days; 10% of patients received granulocyte colony-stimulating factors.1 Anemia occurred in 76% (grade 3 or 4 in 12%) of patients with a median time to onset of 31 days and a median duration of 8 days; 17% of patients received erythropoiesis-stimulating agents and/or blood transfusions.1 Thrombocytopenia occurred in 71% (grade 3 or 4 in 14%) of patients with a median time to onset of 9 days and a median duration of 14 days.1
Among previously treated patients receiving alemtuzumab for B-CLL, grade 3 or 4 neutropenia occurred in 64% of patients with a median duration of 28 days; 17% of patients received granulocyte colony-stimulating factors.1 Grade 3 or 4 anemia occurred in 38% of patients; 66% of patients received erythropoiesis-stimulating agents and/or blood transfusions.1 Grade 3 or 4 thrombocytopenia occurred in 52% of patients with a median duration of 21 days.1 Autoimmune thrombocytopenia, fatal in one case, was reported in 2% of patients receiving alemtuzumab for previously treated B-CLL.1
Severe idiopathic thrombocytopenic purpura (ITP), sometimes fatal, has been reported in 3 patients involved in a clinical trial investigating the use of alemtuzumab for the treatment of multiple sclerosis32 ITP developed about 1-11 months following the last treatment with alemtuzumab.32 One of the 3 patients died from an intracranial hemorrha 2 of the patients, including the patient who died, received cumulative doses of alemtuzumab that exceeded the cumulative weekly dose limit.32 Dosing with alemtuzumab in this clinical trial was suspended.32
Pure red-cell aplasia was caused by parvovirus B19 infection in at least 2 patients receiving alemtuzumab for T-cell malignancies†; the infection was treated with IV immunoglobulin.23, 24
Monitor complete blood cell counts (CBCs) and platelet counts weekly during therapy; more frequent monitoring may be required if worsening anemia, neutropenia, or thrombocytopenia occurs.1 Monitor CD4+ counts following completion of alemtuzumab therapy until levels return to ≥200/mm3.1
Withhold alemtuzumab therapy in patients who develop severe cytopenias except lymphopenia.1 The drug should be discontinued in patients with autoimmune cytopenias or recurrent or persistent severe cytopenias (except lymphopenia).1
Immunosuppression/Infectious Complications
Serious, including fatal, infections can occur in patients receiving alemtuzumab.1 A boxed warning regarding this risk has been included in the prescribing information for alemtuzumab (Campath®).1 Alemtuzumab therapy causes severe and prolonged lymphopenia, which increases the incidence of opportunistic infections.1
Among patients receiving alemtuzumab as first-line therapy for B-CLL in a randomized trial, CMV viremia occurred in 55% and CMV infection occurred in 16% (serious or life-threatening in 5%) of patients.1 Other infections occurred in 74% of patients (198 episodes of infection in 109 patients) and were serious or life-threatening in 21% of patients; 16% of these infections were bacterial, 7% were fungal, 4% were viral, and 73% were caused by an unidentified organism.1 Across all studies, other infections occurred in about 50% of patients.1 Grade 3-5 sepsis was reported in 3-10% of patients in all studies and the incidence was higher in patients receiving alemtuzumab for previously treated disease.1 Grade 3 or 4 febrile neutropenia was reported in 5-10% of patients in all studies and the incidence was higher in patients receiving alemtuzumab for previously treated disease.1 Infection-related fatalities occurred in 2% of patients receiving alemtuzumab as first-line therapy and in 16% of patients receiving the drug as second-line or salvage therapy.1
Patients should be monitored closely for CMV infection during and for at least 2 months following completion of alemtuzumab therapy.1 Withhold therapy for serious infections and during antiviral treatment for CMV infection or confirmed CMV viremia (defined as polymerase chain reaction [PCR] positive CMV in ≥2 consecutive samples obtained 1 week apart).1 Initiate therapeutic ganciclovir (or equivalent) for CMV infection or confirmed CMV viremia.1 In a randomized trial of patients receiving alemtuzumab as first-line therapy for B-CLL, testing for CMV using a PCR assay was performed weekly during therapy and then every 2 weeks for 2 months following the completion of therapy.1 Also monitor for signs and symptoms of Epstein-Barr virus infection.1
If a serious infection occurs, alemtuzumab should be discontinued temporarily;1 therapy may be reinitiated following resolution of the infection.1
Alemtuzumab induces severe and prolonged lymphopenia, which increases the potential for transfusion-associated graft versus host disease (TA-GVHD).1, 2 Only irradiated blood products should be administered unless immediate transfusion is required because of emergency.1
Time to recovery and levels of T-cell counts may vary according to stage of disease and type of therapy in patients receiving alemtuzumab.1 Among patients receiving alemtuzumab as initial therapy, CD4+ T-cell counts recovered to 200/mm3 or greater by 6 months following completion of treatment; at 2 months following completion of treatment, the median CD4+ T-cell count was 183/mm3.1 Among patients receiving alemtuzumab as second-line or salvage therapy, the median time to recovery of CD4+ T-cell counts to at least 200/mm3 was 2 months, but full recovery of CD4+ and CD8+ T-cell counts to baseline levels may take more than 12 months.1
Serious, sometimes fatal, infusion-related reactions, including syncope, pulmonary infiltrates, acute respiratory distress syndrome (ARDS), respiratory arrest, cardiac arrhythmias, myocardial infarction, acute cardiac insufficiency, cardiac arrest, angioedema, and anaphylactoid shock, have been reported.1, 9 A boxed warning regarding this risk has been included in the prescribing information for alemtuzumab (Campath®).1 Acute infusion reactions, including rigors, fever, bronchospasm, chills, nausea, vomiting, rash, urticaria, dyspnea, and hypotension, may occur during or shortly after IV infusion of alemtuzumab.1 These reactions generally occur more frequently during the first week of therapy.1
Among patients receiving alemtuzumab as first-line therapy for B-CLL in a randomized trial, infusion reactions were common, with pyrexia in 69% (grade 3 or 4 in 10%), chills in 53%, hypotension in 16%, urticaria in 16%, and dyspnea in 14% of patients.1
In patients experiencing infusion reactions associated with alemtuzumab, interruption or discontinuance of therapy may be required.1 Medical management (e.g., glucocorticoids, epinephrine, meperidine) should be initiated as clinically indicated.1
Local reactions, including erythema, edema, pruritus, and pain, have been reported, generally during the first 1-2 weeks of therapy, in patients receiving subcutaneous† therapy with alemtuzumab.34, 35, 36 Some experts state that if symptomatic local reactions occur during dosage escalation, the escalation period may be prolonged to up to 2 weeks.34, 36 Some data suggest that injection site reactions to subcutaneous alemtuzumab administration may be more common in patients receiving the drug as first-line therapy for B-CLL than in those with previously treated disease.34, 35, 36
Acute systemic injection-related reactions, including fever and chills/rigors, also have been reported in patients receiving alemtuzumab by subcutaneous injection†, although such reactions appear to occur less frequently with subcutaneous injection than with IV infusion of the drug.34, 35, 36
The safety of immunization with live virus vaccines following alemtuzumab therapy has not been studied.1 However, because of the immunosuppressive effects of alemtuzumab, the manufacturer recommends that live virus vaccines be avoided during therapy with the drug.1
There is potential for immunogenicity with use of therapeutic proteins, such as alemtuzumab.1 Development of antibodies to alemtuzumab has been reported infrequently in patients receiving the drug in clinical trials and does not appear to affect tumor response.1
There are no adequate data in pregnant women; however, the drug may cause fetal harm.1 Embryolethality has been demonstrated in animal studies.1
Advise women of potential risk to the fetus.1
Infants born to pregnant women treated with alemtuzumab may be at increased risk for infections.1
It is not known whether alemtuzumab is distributed into human milk; however, the drug has been detected in milk of lactating mice.1 Because human immunoglobulin G (IgG) is distributed into milk, it is possible that alemtuzumab is distributed into milk.1
Because of the potential for serious adverse reactions from alemtuzumab in a breastfed child, including reduced lymphocyte counts, advise lactating women not to breastfeed during treatment with alemtuzumab and for at least 3 months following the last dose.1
Females and Males of Reproductive Potential
Alemtuzumab may cause fetal harm.1 Pregnancy testing is recommended for females of reproductive potential prior to initiating therapy.1
Advise female patients of reproductive potential to use effective contraception during treatment with alemtuzumab and for at least 3 months after the last dose.1
Based on findings from animal studies, alemtuzumab may impair fertility in females and males of reproductive potential; the reversibility of this effect is not known.1
Safety and efficacy not established in children.1, 5
Clinical studies of alemtuzumab did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients.1 Other clinical experience has not revealed age-related differences in response.1
Safety and efficacy not established in patients with hepatic impairment.1, 5
Safety and efficacy not established in patients with renal impairment.1, 5
The most common serious adverse effects in patients receiving alemtuzumab are cytopenias, infusion reactions, and immunosuppression/infections.1 The most common adverse effects in patients receiving alemtuzumab are infusion reactions (pyrexia, chills, hypotension, urticaria, nausea, rash, tachycardia, dyspnea), cytopenias (neutropenia, lymphopenia, thrombocytopenia, anemia), infections (including CMV viremia and CMV infection), adverse GI effects (nausea, vomiting, diarrhea, abdominal pain), and adverse neurologic effects (insomnia, anxiety).1
No formal drug interaction studies have been performed to date.1, 5
Because of the immunosuppressive effects of alemtuzumab, live virus vaccines should not be administered following a course of alemtuzumab therapy.1
Alemtuzumab, a recombinant DNA-derived humanized anti-CD52 monoclonal antibody (Campath-1H), is an antineoplastic agent.1 The drug is an IgG1 kappa immunoglobulin containing human framework (i.e., variable and constant regions) and murine complementarity-determining regions.1 Alemtuzumab binds specifically to antigen CD52, a glycoprotein expressed on the surface of B and T cells; a majority of monocytes, macrophages, and natural killer (NK) cells; and a subpopulation of granulocytes.1, 2 Following binding of the Fab domain of alemtuzumab to antigen CD52, the Fc domain triggers a host immune response causing lysis of normal and leukemic cells;1, 5 the exact mechanism of cell lysis has not been fully elucidated but is thought to involve complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC).1, 2
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Alemtuzumab (Campath®) is available only through the Campath® Distribution Program.37
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection concentrate, for IV infusion | 30 mg/mL | Campath® |
1. Genzyme. Campath® (alemtuzumab) prescribing information. Cambridge, MA; 2023 Apr.
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4. Keating MJ, Flinn I, Jain V et al. Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood . 2002; 99:3554-61. [PubMed 11986207]
5. Berlex Laboratories, Richmond, CA: Personal communication.
6. Chronic lymphocytic leukemia. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2008 May 16.
7. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414). Rockville, MD; [May 5, 2003]. From FDA web site [Web].
8. Anon. Drugs of choice for cancer. Treat Guidel Med Lett . 2003; 1:41-52. [PubMed 15529105]
9. Food and Drug Administration. MedWatch—Safety-related drug labeling changes: Campath (alemtuzumab) [May 2004]. From FDA web site [Web].
10. Rai KR, Freter CE, Mercier RJ et al. Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine. J Clin Oncol . 2002; 20:3891-7. [PubMed 12228210]
11. Adult non-Hodgkin lymphoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2008 Jun 6.
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13. Enblad G, Hagberg H, Erlanson M et al. A pilot study of alemtuzumab (anti-CD52 monoclonal antibody) therapy for patients with relapsed or chemotherapy-refractory peripheral T-cell lymphomas. Blood . 2004; 103:2920-4. [PubMed 15070664]
14. Kennedy GA, Seymour JF, Wolf M et al. Treatment of patients with advanced mycosis fungoides and Sezary syndrome with alemtuzumab. Eur J Haematol . 2003; 71:250-6. [PubMed 12950233]
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16. Uppenkamp M, Engert A, Diehl V et al. Monoclonal antibody therapy with CAMPATH-1H in patients with relapsed high- and low-grade non-Hodgkin's lymphomas: a multicenter phase I/II study. Ann Hematol . 2002; 81:26-32. [PubMed 11807632]
17. Khorana A, Bunn P, McLaughlin P et al. A phase II multicenter study of CAMPATH-1H antibody in previously treated patients with nonbulky non-Hodgkin's lymphoma. Leuk Lymphoma . 2001; 41:77-87. [PubMed 11342359]
18. Lundin J, Osterborg A, Brittinger G et al. CAMPATH-1H monoclonal antibody in therapy for previously treated low-grade non-Hodgkin's lymphomas: a phase II multicenter study. European Study Group of CAMPATH-1H Treatment in Low-Grade Non-Hodgkin's Lymphoma. J Clin Oncol . 1998; 16:3257-63. [PubMed 9779699]
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20. Osterborg A, Dyer MJ, Bunjes D et al. Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocytic leukemia. European Study Group of CAMPATH-1H Treatment in Chronic Lymphocytic Leukemia. J Clin Oncol . 1997; 15:1567-74. [PubMed 9193354]
21. Lundin J, Kennedy B, Dearden C et al. No cardiac toxicity associated with alemtuzumab therapy for mycosis fungoides/Sezary syndrome. Blood . 2005; 105:4148-9. [PubMed 15867423]
22. Damaj G, Rubio MT, Audard V et al. Severe cardiac toxicity after monoclonal antibody therapy. Eur J Haematol . 2002; 68:324. [PubMed 12144543]
23. Herbert KE, Prince HM, Westerman DA. Pure red-cell aplasia due to parvovirus B19 infection in a patient treated with alemtuzumab. Blood . 2003; 101:1654. [PubMed 12560244]
24. Crowley B, Woodcock B. Red cell aplasia due to parvovirus b19 in a patient treated with alemtuzumab. Br J Haematol . 2002; 119:279-80. [PubMed 12358942]
25. Pawson R, Dyer MJ, Barge R et al. Treatment of T-cell prolymphocytic leukemia with human CD52 antibody. J Clin Oncol . 1997; 15:2667-72. [PubMed 9215839]
26. Dearden CE, Matutes E, Cazin B et al. High remission rate in T-cell prolymphocytic leukemia with CAMPATH-1H. Blood . 2001; 98:1721-6. [PubMed 11535503]
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