alemtuzumab (Campath, Lemtrada)

Dosing and uses of Campath, Lemtrada (alemtuzumab)

• Adult
• Pediatric

 

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