THERAPY
Lemtrada
Coverage
Protocols
Before Initiation of Therapy
- CBC, creatinine, TSH, AST, ALT, LDH, bilirubin, HIV, VZV IgG, measles IgG, HepBsAg, HepBcAb, HepBsAb, HepC Ab, Pap test for HPV, urine analysis, urine albumine/creatinine ratio
- Pregnancy test
- ECG
- Chest Xray and/or Quantiferon
- Immunization should be brought up to date and vaccination for Pneumococcus and Haemophilus Influenza type B and VZV should be done
- HPV vaccination for unvaccinated patients less than 25 years old or sexually active adults not in a long term relationship should be done preferably completed >4 weeks prior to receiving Alemtuzumab
- Brain MRI unless recently (<3 months) done
- When switching from Gilenya (fingolimod) a normalized lymphocyte count is recommended
- When switching from Aubagio, cholestyramine 8 gms Q8H PO X 11 days or until serum levels are less than 0.02mg/L is recommended
- When switching from Tysabri a less than 2 month washout period, serum JCV index and baseline brain MRI with CSF PCR for JCV is recommended
- High blood pressure should be adequately controlled prior to initiating treatment
- Live vaccines are contraindicated from 6 weeks prior to the first treatment to the normalization of the immune cells following the last treatment of Lemtrada
During the intravenous treatment
The first 5 day cycle should be spread over 2 weeks to minimize infusion related complications. Subsequent 3 day cycles are usually accompanied by less complications/ side effects and can be accomplished within 1 week period.
Premedications of benadryl 50mg, tylenol 1.0gm, solumedrol 1gm are administered prior to infusing Lemtrada. The solumedrol dose can be reduced to 500mg in subsequent days according to the severity of alemtuzumab versus solumedrol side effects.
Atarax 10-20mg HS and QID PRN is added to reduce the incidence of rash and insomnia.
Acyclovir 200mg daily PO is initiated and continued for 1 month or longer according to prior HSV history and current symptoms.
Monitor and maintain near normal blood pressure ( less than 165 systolic) using rapid acting anti hypertensive medications ( captopril, labetolol, clonidine, clevidipine, fenoldopam) and/or slowing down or interrupting the infusion in order to avoid cerebrovascular complications.
Prednisone 500mg - 1.0gm PO daily x 3 may be required to attenuate symptoms related to Lemtrada induced pseudo relapse that may occur in the days following the initial 5 day treatment or acute alveolar hemorrhage or interstitial pneumonitis that may occur during or weeks post Lemtrada treatment.
The highest risk for infection is in the first month post treatment therefore Septra DS 1 tab 3xweek or ciprofloxacin 125 mg daily for 1 month .
Monitoring Until 48 Months Post Last Therapy
- Monthly CBC, creatinine, urine analysis, AST, ALT, LDH, bilirubin
- Q3months TSH
- Annual PAP test for HPV positive patients
- If the urine analysis is abnormal repeat the urine albumin/creatinine ratio and if the latter is abnormal then a 24hrs urine collection and referral to a nephrologist are recommended
Studies
Product Monograph
Specific Concerns
Secondary Autoimmune Disorders
The prevalence of Lemtrada induced secondary autoimmune disorders has been estimated at 40 to 50% over a 5 year period following the initiation of Lemtrada. It was initially believed to be limited to a few conditions thyroid (hypo/hyper) immune thrombocytopenic purpura and Good Pasture like syndrome. It has since became clear that any organ/system can be affected including autoimmune hepatitis, hemophagocytic lymphohistiocytosis, vitiligo, arthritis, hemolytic anemia, agranulocytosis etc . Thyroid disorders thankfully represents the great majority of the cases. The incidence is highest in the second and third years following the first treatment. Different strategies are being investigated to reduce the incidence. Treatment starts with early detection through monthly laboratory testing and often involves steroids, plasmapheresis or use of an anti CD20 . Case reports however of interstitial pneumonitis and alveolar hemorrhages have been reported occurring during or shortly after a cycle of Lemtrada.
Infection
Fatal infections have been reported often within the first month of treatment initiation including septic shock, listeriosis, aspergillosis, and pneumonia. We suggest adding preventative antibiotic therapy such as Septra or ciprofloxacin to acyclovir during the first month.
Cerebrovascular disorders
Cerebrovascular accident from carotid dissection and cerebral hemorrhage have been reported as a complication during the second half of the first cycle or shortly after. Close blood pressure monitoring and treatment are recommended.