alemtuzumab (Campath, Lemtrada)
Classes: Antineoplastics, Monoclonal Antibody; Multiple Sclerosis Treatments
Dosing and uses of Campath, Lemtrada (alemtuzumab)
Adult dosage forms and strengths
injectable IV solution
- 10mg/mL (Lemtrada; 1.2mL/vial[12mg/1.2mL])
- 30mg/mL (Campath; 1mL/vial)
- CamPath and Lemtrada are available only from a restricted distribution program
Chronic Lymphocytic Leukemia (Campath)
Campath is indicated as a single agent for treatment of B-cell CLL
Gradually escalate to maximum recommended single dose of 30 mg (typically over 3-7 days)
Escalation is required at initiation of dosing or if dose is held ≥7 days during treatment
Escalation strategy
- Administer 3 mg IV qDay infused over 2 hr until infusion reactions are ≤Grade 2, THEN
- Administer 10 mg IV qDay until infusion reactions are ≤Grade 2, THEN
- Administer 30 mg IV 3x/week (on alternate days (eg, Mon-Wed-Fri)
- Duration of treatment: 12 weeks (including escalation periods)
- Not to exceed 30 mg/dose OR 90 mg/week (increased risk for pancytopenia)
Dosage modifications (Campath)
- Withhold/decrease dose/discontinue for ANC <250/microL and/or platelet count ≤25,000/microL (see prescribing information for details)
- Withhold during serious infection or other serious adverse reactions until resolution
- Discontinue for autoimmune anemia or autoimmune thrombocytopenia
- No dose modifications recommended for lymphopenia
Premedication and infection prophylaxis (Campath)
- Premedicate with diphenhydramine 50 mg and acetaminophen 500-1000 mg PO 30 minutes before first infusion and each dose escalation
- Administer trimethoprim/sulfamethoxazole DS PO BID 3x/week (or equivalent) for Pneumocystis jiroveci pneumonia (PCP) prophylaxis
- Administer famciclovir 250 mg PO BID (or equivalent) as herpetic prophylaxis
- Continue PCP and herpes viral prophylaxis for a minimum of 2 months after treatment completion or until the CD4+ count is ≥200 cells/microL, whichever occurs later
- Monitor CBC, platelets, CD4+ counts qWeek
Multiple Sclerosis (Lemtrada)
Lemtrada is indicated for relapsing forms of multiple sclerosis (MS); because of its safety profile, reserve use for patients who have an inadequate response to ≥2 other drugs for Ms
Recommended dose is administered as 2 separate treatment courses
First treatment course: 12 mg/day IV on 5 consecutive days (60 mg total dose)
Second treatment course: 12 mg/day on 3 consecutive days (36 mg total dose) given 12 months after the first treatment course
Vaccinations (Lemtrada)
- Complete necessary immunizations at least 6 wk before administration of alemtuzumab
- Before treatment, determine whether patients have a history of varicella or have been vaccinated for varicella zoster virus (VZV); if not, test the patient for antibodies to VZV and consider vaccination for those who are antibody-negative
- Postpone treatment with alemtuzumab until 6 weeks after VZV vaccination
Premedication and infection prophylaxis (Lemtrada)
- Corticosteroids: Premedication with high-dose corticosteroids (eg, 1,000 mg methylprednisolone) immediately before alemtuzumab IV infusion and for the first 3 days of each treatment course
- Herpes prophylaxis: Administer antiviral prophylaxis for herpetic viral infections starting on the first day of each treatment course and continue for a minimum of 2 months following or until CD4+ count is ≥200 cells/microL
Kidney Transplantation (Off-label)
Used as part of various induction regimens in patients undergoing kidney transplantation
In numerous phase 3 clinical trials, use has achieved steroid-sparing effects including improved glycemic stability
Leukopenia and neutropenia were reported
Careful patient selection is required
Long-term follow-up results from the 3C trial (NCT01120028) is pending regarding alemtuzumab’s role in reducing calcineurin inhibitor exposure by using a more potent induction regimen
Pediatric dosage forms and strengths
Safety and efficacy not established
Campath, Lemtrada (alemtuzumab) adverse (side) effects
>10% (Campath)
Rigors (86%)
Fever (85%)
Neutropenia (85%)
Anemia (80%)
Thrombocytopenia (72%)
Nausea (54%)
Vomiting (41%)
Rash (40%)
Fatigue (34%)
Dyspnea (26%)
Cough (25%)
Headache (24%)
Pruritus (24%)
Sepsis (24%)
Skeletal pain (24%)
Diarrhea (22%)
Anorexia (20%)
Excessive sweating (19%)
Pneumonia (16%)
Dysthesias (15%)
Stomatitis (14%)
Asthenia (13%)
Edema (13%)
Dizziness (12%)
Abdominal pain (11%)
Herpes simplex (11%)
Hypertension (11%)
Myalgias (11%)
Tachycardia, SVT (11%)
>10% (Lemtrada)
Infusion reactions, all (92%)
Infections, all (71%)
Rash (53%)
Headache (52%)
Pyrexia (29%)
Nasopharyngitis (25%)
Nausea (21%)
Urinary tract infection (19%)
Fatigue (18%)
Insomnia (16%)
Upper respiratory tract infection (16%)
Herpes viral infection (16%)
Urticaria (16%)
Pruritus (14%)
Thyroid gland disorders (13%)
Fungal infection (13%)
Arthralgia (12%)
Pain in extremity (12%)
Back pain (12%)
Diarrhea (12%)
Sinusitis (11%)
Oropharyngeal pain (11%)
1-10% (Campath)
Chest/back pain (10%)
Dyspepsia (10%)
Insomnia (10%)
Bronchospasm (9%)
Constipation (9%)
Depression (7%)
Epistaxis (7%)
Moniliasis (8%)
Pancytopenia (5%)
Somnolence (5%)
1-10% (Lemtrada)
Paresthesia (10%)
Dizziness (10%)
Abdominal pain (10%)
Flushing (10%)
Vomiting (10%)
Cough (9%)
Chills (9%)
Dysgeusia (8%)
Influenza (8%)
Dermatitis (8%)
Dyspepsia (8%)
Blood in urine (8%)
Dyspnea (8%)
Tachycardia (8%)
Anxiety (7%)
Muscular weakness (7%)
Bronchitis (7%)
Chest discomfort (7%)
Muscle spasm (6%)
Myalgia (6%)
Decreased CD4 and CD8 lymphocytes (6%)
Asthenia (5%)
Infusion reactions, serious (3%)
Infections, serious (3%)
Immune thrombocytopenia (2%)
HPV infection (2%)
<1% (Lemtrada)
Pneumonitis (0.5%)
Glomerular nephropathies (0.3%)
Thyroid cancer (0.3%)
Melanoma (0.3%)
Active/latent tuberculosis (0.3%)
Hemolytic anemia (0.2%)
Pancytopenia (0.2%)
Neutropenia (0.1%)
Warnings
Black box warnings
Cytopenias
- Serious cytopenias, including fatal pancytopenia/marrow hypoplasia, autoimmune idiopathic thrombocytopenia, and autoimmune hemolytic anemia, can occur with this drug
- Single doses >30 mg or cumulative doses >90 mg/week per week increase the incidence of pancytopenia
- Monitor CBC with differential, serum creatinine, and urinalysis at periodic intervals for 48 months after the last dose
Infusion reactions
- Administration of this drug can result in serious infusion reactions, including fatal reactions
- Administer in a setting with appropriate equipment and personnel to manage anaphylaxis or serious infusion reactions
- Monitor patients during infusions and for 2 hr after each infusion, withhold the drug for Grade 3 or 4 infusion reactions
- Gradually escalate the drug to recommended dose at initiation of therapy and after interruption of therapy for 7 or more days
Infections
- Serious infections, including fatal bacterial, viral, fungal, and protozoan infections, have been reported with this drug
- Administer prophylaxis against Pneumocystis jiroveci pneumonia (PCP) and herpes virus infections
Malignancies
- May cause an increased risk of malignancies, including thyroid cancer, melanoma, and lymphoproliferative disorders
- Perform yearly skin exams
REMs
- Campath and Lemtrada are available only through restricted distribution under a Risk Evaluation Mitigation Strategy (REMS) program
- Campath: 1-877-422-6728
- Lemtrada: 1-855-676-6326
Contraindications
Campath: None
Lemtrada: Patients infected with HIV because alemtuzumab prolongs reduction of CD4+ lymphocyte counts
Cautions
Campath
- Prophylactic treatment against PCP pneumonia and herpes viral infections recommended from initiation of treatment until 2 months following last dose (or until CD4+ >200/mcL)
- Hold treatment if ANC <250/mcL and/or platelets <25,000/mcL; if this occurs 3 times, discontinue treatment permanently
- Withhold if severe infection
- Discontinue if autoimmune anemia or autoimmune thrombocytopenia
- Use effective contraception during treatment and for 6 mth following treatment
- Ischemic heart disease, hypotension, live vaccine within 3 months
- Risk of serious infusion reactions; interrupt if Grade 3 or 4 infusions reactions
Lemtrada
- Autoantibody formation may occur and increase risk of serious autoimmune conditions (eg, thyroid disorders, immune thrombocytopenia, hemolytic anemia, pancytopenia, glomerular nephropathies, connective tissue disorders, and acquired hemophilia A) (see Black box warnings)
- Infusion reactions are common (92%) and may be serious or life-threatening; premedication with corticosteroids is required and monitoring (see Black box warnings)
- May increase risk for malignancies, including thyroid cancer, melanoma, lymphoproliferative disorders, and lymphoma (see Black box warnings)
- Infections occurred in 71% of alemtuzumab-treated patients compared with 53% of those treated with interferon beta-1a; reported infections include herpes viral infections, HPV, tuberculosis, fungal infections (especially oral and vaginal candidiasis), and listeria meningitis; patients with HBV or HCV were excluded from clinical trials
- Pneumonitis reported; advise patients to contact physician with symptoms of SOB, cough, wheezing, chest pain/tightness, or hemoptysis
- Increased vigilance and monitoring is warranted in patients previously treated with alemtuzumab (Campath) for CLL who receive Lemtrada for MS; additive and chronic autoimmune effects may occur
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown if excreted in human breast milk; a decision should be made whether to discontinue nursing or discontinue the drugs, taking into account the importance of the drug to the mother
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Campath, Lemtrada (alemtuzumab)
Mechanism of action
Recombinant monoclonal antibody against CD52 (lymphocyte antigen); promotes antibody-dependent lysis
Pharmacokinetics
Half-Life: 12 days
Vd: 14.1 L; largely confined to blood and interstitial space
Metabolism: unknown
Excretion: unknown
Administration
IV Incompatibilities
Do not admix with any other drug; do not administer simultaneously in the same IV line
IV Preparation
Strict aseptic technique must be observed in preparing and administering
Withdraw dose into a syringe and filter with a sterile, low-protein-binding, non-fiber-releasing 5 micron filter prior to dilution
Dilute in 100 mL of NS or D5W; invert bag gently to mix solution
IV Administration
Administer by IV infusion only, do NOT give as IV push or bolus
Campath: Administer over 2 hr
Lemtrada: Administer over 4 hr; extend duration of infusion if clinically warranted
Do not shake prior to use
No incompatibilities have been observed between alemtuzumab solution and PVC bags, PVC or polyethylene-lined PVC administration sets, or low-protein-binding filters
Storage
Unopened vials: Refrigerate at 2-8°C (36-46°F)
Diluted solution: Start infusion within 8 hr after dilution (no preservatives); may store at room temperature or refrigerate at 2-8°C (36-46°F)
Do not freeze or shake
Store in original carton to protect from light