Seroconversion after CD20 depletion…Prepare for a delay?

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There are going to be two schools of thought on how to deal with lack of seroconversion to the vaccine.

Ignore the issue or do something about it.

You can

1. Toe the party line and carry on dosing according to the label. This is going to result in happy pharma, ease of choice for many people but the liklihood that many people are not going to seroconvert after COVID-19 vaccination and perhaps expose people if they get infected with SARS-CoV-2

2. Delay the next dosing of anti-CD20 to try and allow a vaccine -related antibody response in the hope that it helps protect against COVID-19.

So what you do depends on what you think are the risks of COVID-19 are and how good you see the value of seroconversion.

It is not my job to tell you our your neuro what to do. However, if I can help supply informatation to help you make informed choices then I am doing a job.

There is not yet too much information in MS, but the information coming from arthritis and cancer is highly consistent

It suggests that:

If you did not make a response after two vaccine doses most people will not give a response to a third vaccine dose if you are taking an anti-CD20 depleting antibody

Vaccine response relates to B cell repopulation and this takes time

To make a COVID-19 response on ocrelizumab you will probably need to delay the CD20. This is because it is a strong depleter and much better than rituximab at depleting and so will stop B cells repopulating

Will this work off a single booster?

Will disease reactivate if you delay?

How long would you need to delay?

I have to say this is not really clear yet, and the issue with reactivation may depend how long you have been on treatment and stable but the need for delay is a consistent feature and is seen in a number of conditions

High Seroconversion Rates Amongst Black and Hispanics With Hematologic Malignancies after SARS-CoV-2 VaccinationShapiro, L. C., Thakkar, A., Gali, R., Gonzalez-Lugo, J. D., Bazarbachi, A.-H., Rahman, S., Pradhan, K., Fehn, K., Abreu, M., Kornblum, N., Gritsman, K., Goldfinger, M., Shastri, A., Mantzaris, I., Braunschweig, I., Halmos, B., Verma, A., McCort, M., Bachier-Rodriguez, L., Sica, R. A.10.1101/2021.09.13.21263365 — Posted: 2021-09-16

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Treatment Positive Negative

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Anti-CD20 antibody therapy, n (%)
Less than 6 months 5/12 (42%) 7/12 (58%)
Greater than 6 months 17/24 (71%) 7/24 (29%)

CAR-T Greater than 1 year 0/5 (0%) 5/5 (100%
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CAR-T is going to destroy your B cells and so it will block vaccine responses

However the level of seroconversion depends on the study. In this study it was over 70% after two jabs. However it was over 90% use of rituximab and not ocrelizumab. I understand about 20% replete to 1% by 6 months with rituximan it is less than 5% on ocrelizumab based on the phase II extension data

Kornek et al. Distinct Patterns of Humoral and Cellular Immune Responses Following SARS-CoV-2 mRNA Vaccination in Patients With Immune-Mediated Neurological Disorders on Anti-CD20 Therapy: A Prospective Cohort Study. SSRN  https://ssrn.com/abstract=3924204

Background: Patients with neuroimmunological disorders on anti-CD20 therapy are at increased risk of severe COVID-19. However, little is known about SARS-CoV-2 vaccine efficacy in this cohort. In particular, the impact of B cell depletion on humoral and cellular immune responses to SARS-CoV-2 vaccination remains poorly defined. No study has addressed vaccine responses to the SARS-CoV-2 delta variant in immunocompromised individuals so far.

Methods: In this prospective cohort study we investigated humoral and cellular responses in serial samples from 164 individuals after SARS-CoV-2 mRNA vaccination (82 patients with neuroimmunological disorders on anti-CD20 therapy and 82 healthy controls). Antibodies were quantified using the Elecsys anti-SARS-CoV-2 S immunoassay against the receptor-binding (RBD) domain. T cell responses against the SARS-CoV-2 Wuhan strain and the delta variant were assessed by IFN-g enzyme-linked immunosorbent spot assays. 

Findings: Following vaccination, SARS-CoV-2 –specific antibodies were detected in 57/82 (70%) patients compared to 82/82 (100%) healthy controls (p<0·001). Seroconversion rates and antibody levels were lower in B cell-depleted (<1 B cell/mcl) patients compared to non-depleted (≥ 1 B cell/mcl) patients (p<0·001). B cell levels ≥ 1 cell/mcl were sufficient to induce anti-SARS-CoV-2-S antibody responses. In contrast to the antibody response, most B cell-depleted patients generated a T-cell response against the SARS-CoV-2 Wuhan strain and the delta variant that was more robust in frequency (p<0·05) and magnitude (p<0·01) compared to non-depleted patients and persisted for at least six weeks.

Interpretation: Humoral immunity following SARS-CoV-2 mRNA vaccination can be achieved in patients on anti-CD20 therapy once B cells start to repopulate. In the absence of B cells, a robust and stable T cell response is generated which may provide a potent defense against severe COVID-19 in this high-risk patient population. 

V1 = baselineV2 after first vaccine and V3 after second vaccine

Seroconversion relates to B cell repopulation although this is not absolute

So it says what many other studies are saying and B cells need to repopulate to make an antibody response. However the vast majority of people in this study (~90%) were taking rituximab and you and I know that ocrelizumab is much better at depleting B cells than rituximab.

General Disclaimer: Please note that the opinions expressed here are those of the author and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice. 

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MouseDoctor

12 comments

    • Im afraid not…however I am doing COVID work at the moment, and there is not much MS Stuff that has not been covered before.

  • MD thanks for this it’s clear those without antibodies aren’t at risk. Rather than do nothing or delay your next indication hopefully there will be other solutions – antibody infusions for example. A non vaccine solution is needed that won’t risk MS treatment efficacy! Hopefully this is in the works

      • Is there any way to determine if one is being over or under dosed? I don’t want to have unnecessary drugs but nor do I want to risk my MS acting up because it is not sufficiently treated.

          • BMI or overall mass?

            Take ocrelizumab as an example with the 600mg dose. Was that decided as the ideal amount for the combination in the ideal patient of a particular gender, ethnicity, mass and BMI?

            Or was it a more general TLAR (That Looks About Right) guesstimated nice round number?

            On the face of it, the one-size-fits-all 600mg dose does seem a little unscientific.

  • Seems like we should start considering which vaccine to take as well. If Pfizer antibodies wane after 6-8 months but Moderna or AZ/Oxford don’t, then we’d probably want to boost MS’ers with Moderna or AZ/Oxford.

    • The JCVI have stated RNA vaccines for the boosters….The AZ vaccine is not good enough for immunosuppressed people as it gives a low titre to no existant response. Moderna gives the highest antibody levels

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