Vaccination and ALEmtuzumab: ALE when?
When, why and against what should patients with multiple sclerosis treated with alemtuzumab be vaccinated? And is vaccination effective in this population?
Alemtuzumab is no “small potato”
Alemtuzumab is a humanized monoclonal antibody against the surface glycoprotein CD52, present in high concentrations on T (CD3+) and B (CD19+) lymphocytes and in lower levels on NK cells, monocytes, and macrophages. CD52 is detected very little or not at all on neutrophils, plasma cells, or bone marrow stem cells. Binding to the surface of T and B lymphocytes causes lysis of these lymphocytes.
Alemtuzumab is among the multiple sclerosis disease-modifying therapies (DMDs) with the greatest immunosuppressive effect. This also accounts for its excellent efficacy. However, there is a flip side – in a registration clinical trial, 71% of patients experienced infectious complications, and 2.7% had severe infections. The depletion of immune cells not only increases the likelihood of infection and its severity but also affects the immune system's response to vaccination.
When it's not feasible in advance
It is recommended that local immunization requirements be met at least 6 weeks before initiating alemtuzumab treatment. Crucial vaccinations include those against varicella zoster virus and tetanus, and potentially against human papillomavirus (HPV). But how do patients already being treated with alemtuzumab respond to vaccination?
This question became particularly relevant with the advent of COVID-19. Because it was a new infection with new vaccines, the issue of vaccination also needed to be addressed in patients already receiving alemtuzumab therapy. The CovaXiMS study evaluated the immune response to 2 doses of mRNA vaccines (26 Comirnaty, 8 Spikevax) in 34 patients (average age 38 years, 74% women, all with relapsing-remitting MS, average interval since the last alemtuzumab infusion was 784 days). A total of 23 patients (68%) had their last infusion less than 2.5 years before vaccination. Antibody levels 4 weeks after the second dose were relatively high and comparable to levels in patients with MS treated with other DMDs. Antibody levels didn't correlate with the time since the last alemtuzumab infusion (r = 0.14; p = 0.42). No breakthrough infections were observed during the subsequent 6-month follow-up.
Four patients described in a paper published in the journal Multiple Sclerosis and Related Disorders also developed an antibody response. The average time from the last alemtuzumab dose to vaccination was 7.1 ± 3.6 months (range 2–10). The average time from the last vaccine dose to detecting a protective antibody titer was 1.5 ± 1.0 months (range 1–3). The SARS-CoV-2 IgG titer post-vaccination was 74.3 ± 34.8 for the Comirnaty vaccine and 73 for the patient vaccinated with the Sinopharm vaccine.
The retained ability to mount a humoral immune response to other vaccines (diphtheria, tetanus, and poliomyelitis vaccines, conjugate vaccine against Haemophilus influenzae type b and meningococci group C, and pneumococcal polysaccharide vaccine) was confirmed in a pilot study with 24 MS patients published in the journal Neurology. The median time from the last alemtuzumab dose to vaccination in this study was 18 months (range 1.5–86).
Everything has its time
Vaccination in patients treated with alemtuzumab makes sense and ideally should be completed before starting the treatment. However, if administration cannot be postponed or if the vaccine needs to be given during therapy, it is necessary to wait for the lymphocyte count to rise to at least 0.8 × 109/l – usually 3–6 months.
(dos)
Sources:
1. Sormani M. P., Salvetti M., Uccelli A. COVID-19 severity and vaccination effect in persons with MS treated with alemtuzumab. Mult Scler J 2022; 28 (3 Suppl.): 229.
2. Drulovic J., Ivanovic J., Martinovic V. et al. Humoral response to SARS-CoV-2 COVID-19 vaccines in patients with multiple sclerosis treated with immune reconstitution therapies. Mult Scler Relat Disord 2021; 54: 103150, doi: 10.1016/j.msard.2021.103150.
3. McCarthy C. L., Tuohy O., Compston D. A. S. et al. Immune competence after alemtuzumab treatment of multiple sclerosis. Neurology 2013; 81 (10): 872–876, doi: 10.1212/WNL.0b013e3182a35215.
4. SPC Lemtrada. Available at: www.ema.europa.eu/en/documents/product-information/lemtrada-epar-product-information_cs.pdf
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