Case study: Switching from Ocrelizumab to Alemtuzumab

In this case study Prof G discusses the nuts and bolts of switching from ocrelizumab (anti-CD20) to alemtuzumab (anti-CD52) for vaccine readiness and perceived higher efficacy.

Case Study

Dear Prof G

I am a 56-year old male who has been on ocrelizumab for just shy of 2 years, i.e. have had four cycles of ocrelizumab treatment with my next course due in early October, which is approximately 2 months from now.  

Before starting ocrelizumab I had been on dimethyl fumarate (Tecfidera) for 33 months. I requested to switch to ocrelizumab because I noticed my condition was gradually worsening, particularly my gait and balance. At the time I had not had any obvious relapses, but my MRI did show two new lesions and one lesion that had enlarged. 

I have been particularly careful to socially isolate myself during the COVID-19 pandemic and have not had COVID-19. I have had two doses of the Pfizer-BioNTech mRNA COVID-19 vaccine and disappointedly discovered that I have not seroconverted.  After doing my own research I realise I don’t want to remain on ocrelizumab long-term and want to escalate my treatment to alemtuzumab. My decision to choose alemtuzumab is based on its apparent superiority to ocrelizumab on long term disability and brain volume loss and the fact it does not cause long term immunosuppression. The latter is very important to me as I want to be able to respond to the COVID-19 booster vaccine and other vaccines in the future. 

Fortunately, my neurologist has been very accommodating and has agreed to the switch. Can you please advise on the timing of the switch and how it should be done? 

Thank you.

Patient D

Prof G’s Response

I have discussed switching from ocrelizumab or other anti-CD20 therapies in a prior MS-Selfie Newsletter. 

The proposed switch above from ocrelizumab (anti-CD20) to alemtuzumab (anti-CD52) in this case is not for evident inflammatory disease activity or EIDA, but vaccine readiness and the perception that alemtuzumab will be more effective than ocrelizumab on MS outcomes. Are these assumptions correct? 

This person can address vaccine readiness by simply delaying or missing his next dose of ocrelizumab and waiting for some recovery of his B-cells in the peripheral blood. How long he will have to wait to be vaccine ready is not easy to predict as there are some people with MS (pwMS) who repopulate their B-cells very quickly and those that repopulate them very slowly. 

The so-called median time for B-cell counts to return to either baseline or the lower limit of normal is approximately 72 weeks with a range of 27-175 weeks after the last dose of ocrelizumab (FDA datasheet). After a period of no treatment for  2.5 years, B-cell counts return to baseline or the lower limit of normal in 90% of patients. Early vaccine studies suggest antibody responses to the COVID-19  vaccine occur in people treated with anti-CD20 therapies (rituximab or ocrelizumab) with only partial recovery of their B-cells, i.e. when their counts go above 10 CD19+ B-cells/mm3. 

Will alemtuzumab be superior to ocrelizumab in this patient? I don’t know. This patient is relatively old and his disease duration is over 5 years. Therefore he is not representative of the population of pwMS who were studied on the so-called CARE-MS 2 study of non-DMT naive patients receiving alemtuzumab after having a suboptimal response to another DMT.  Therefore, we don’t have any class 1 evidence of the effectiveness of alemtuzumab in this patient. What we do know is that because of his age he is more likely to develop some of the vascular complications associated with alemtuzumab, i.e. stroke, intracranial haemorrhage and myocardial infarction. He needs to be made aware of this.

This patient needs to be aware that the benefit:risk ratio of alemtuzumab is not as favourable as it would have been if he had been offered alemtuzumab several years earlier. He also needs to sign-up for all the monitoring requirements and potential side effects that come with alemtuzumab treatment. 

In this particular switch not waiting for complete B-cell reconstitution is likely to result in a delayed B-cell repopulation after at least the first course of alemtuzumab. This has been hypothesised to reduce his chances of developing a secondary autoimmune disease as a complication of alemtuzumab treatment. Please note this is theoretical and the evidence that pretreatment with an anti-CD20 or simultaneous use of an anti-CD20, therapy with alemtuzumab reduces the risk of secondary autoimmunity needs further exploration. 

If this was my patient I would not give him his next dose of ocrelizumab and I will check his peripheral blood CD19+ve B-cell counts in January and if necessary monthly thereafter.  Once his B-cell counts are above 10/mm3 I would give his booster COVID-19 vaccine and any other vaccines that are required, i.e. seasonal flu vaccine and possibly the pneumococcal vaccine. At this point, I would do all the pre-alemtuzumab blood tests and screens, start him on a diet to prevent Listeriosis in combination with cotrimoxazole prophylaxis and give him his first course of alemtuzumab 3-4 weeks after his vaccination(s). The 3-4 week delay will hopefully allow him to make an appropriate vaccine response. 

In the interim, I will make him aware that his immunity to SARS-CoV-2 is suboptimal and he needs to remain vigilant and avoid high-risk environments regarding potential exposure to SARS-CoV-2. 

Please note that I am not agreeing or disagreeing with this patient’s decision to switch from ocrelizumab to alemtuzumab. I understand his reasons for wanting to switch and I am simply supporting him in doing so.  

MS-Selfie

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General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust. The advice is intended as general advice and should not be interpreted as being personal clinical advice. The above case history is based on a patient who contacted Professor Giovannoni for advice. However, the details of this specific case above are fictionalised. If you have problems please contact your own healthcare professional who will be able to help you.