ALEMTUZUMAB INJ,SOLN

Clinical Criteria Summary

Secondary progressive MS with no clinical or MRI evidence of relapses
Concurrent use of immune system modifying drugs (DMT) to treat MS (interferon beta-1B, glatiramer acetate, interferon beta 1A, natalizumab, mitoxantrone), unless the previous agent is discontinued when alemtuzumab is initiated
Infection with Human Immunodeficiency Virus
No documented baseline testing within 30 days prior to initiation: CBC with differential, LFT, and skin exam
Positive test for tuberculosis

Patients with relapsing MS characterized by clearly defined acute attacks with full or partial recovery
Must be prescribed and monitored by a VA neurologist or locally designated MS Specialist
AND meet at least one of the following conditions:
Loss of clinical response or intolerance to at least two DMTs (injectable: interferon beta 1a, interferon beta 1b, glatiramer; oral: dimethyl fumarate, fingolimod, teriflunomide); if serum JCV Ab negative, a trial of natalizumab is required
Currently on natalizumab therapy with development of risk factors for PML (duration > 24 months, anti JC virus antibody positive, or received immunosuppressant therapy prior to natalizumab)
Highly aggressive disease demonstrated by heavy burden of MRI T2 lesions, presence of multiple enhancing lesions at onset, high burden of gadolinium enhancing lesions, or rapid accrual of disability

Recommended dosage: 12 mg/day administered by intravenous infusion for 5 consecutive days, followed by three consecutive daily infusions 1 year later
Subsequent treatment courses: 12 mg per day on 3 consecutive days (36 mg total dose) may be administered as needed, at least 12 months after the last dose of any prior treatment course
Must be administered in a setting with appropriate equipment and personnel to manage anaphylaxis or serious infusion reactions
Monitor patients for 2 hours after each infusion; inform patients that serious infusion reactions can also occur after the 2-hour monitoring period

High dose corticosteroids (1,000 mg methylprednisolone or equivalent) immediately prior to alemtuzumab infusion and for the first 3 days of each treatment course
Anti-viral prophylaxis for herpetic viral infections starting on the first day of each treatment course, continuing for a minimum of two months following treatment or until CD4+ lymphocyte count is > 200 cells per microliter (whichever occurs later)

CBC with differential, serum creatinine levels, and urinalysis with urine cell counts and urine protein to creatinine ratio: prior to initiation and monthly until 48 months after the last infusion
Thyroid function tests: prior to initiation and every 3 months until 48 months after the last infusion (monitoring may continue past 48 months based on clinical findings)
Skin examination for melanoma: prior to treatment and yearly thereafter
HPV screening for female patients: annually
Annual brain MRI by CMSC Protocol

Available only through restricted distribution under a Risk Evaluation Mitigation Strategy (REMS) program due to risks of autoimmunity, infusion reactions, and malignancies
Black Box Warning for serious, sometimes fatal autoimmune conditions such as immune thrombocytopenia and antiglomerular basement membrane disease (anti-GBM)
Anti-GBM disease may develop end-stage renal disease requiring dialysis or renal transplantation; alveolar hemorrhage (hemoptysis) is a common component; cases diagnosed up to 40 months after the last dose
Associated with increased risk of malignancies, including thyroid cancer, melanoma, and lymphoproliferative disorders

Serious and life-threatening stroke (ischemic and hemorrhagic) reported within 3 days; instruct patients to seek immediate medical attention if symptoms occur
Evaluate for varicella zoster virus infection history or vaccination prior to initiation; if negative, vaccinate with live varicella virus product (Varivax®), wait at least six weeks after completing two doses before initiating therapy
Do not administer live viral vaccines for at least 2 months after a course or until CD4+ lymphocyte count is > 200 cells per microliter
Consider delaying alemtuzumab in persons with active infection until the infection is fully controlled
Fungal infections and Listeria meningitis occur with increased frequency; counsel patients to not consume foods associated with Listeria prior to infusion
Symptoms of Listeria infection can be difficult to distinguish from infusion reactions

IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course

Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
Routine: CBC w/ diff, CMP, TSH, LFT, and UA
Has a REMS program which also provides lab and imaging frequency guidance

Delay treatment if active skin infection
Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter

Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing

An appropriate washout time from previous DMT is unknown
The risks of a longer washout period should be weighed against the risks of another relapse
Additive immunosuppression should be considered
If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks