Cellular and humoral immune response to SARS-CoV-2 mRNA vaccines in patients treated with either Ibrutinib or Rituximab

[gardening-girl]

For more than a year we have been reminding each other that even if we don't produce antibodies in response to covid vaccination, we may still produce a cellular response, that is a response that puts our T-cells on guard to fight a covid infection.

The study cited below provides data to back up that idea, at least for some of us.

Abstract:

Patients treated with B-cell-targeting therapies like Rituximab or Ibrutinib have decreased serological response to various vaccines. In this study, we tested serological and cellular response to SARS-CoV-2 mRNA vaccines in 16 patients treated with Ibrutinib, 16 treated with maintenance Rituximab, 18 patients with chronic lymphocytic leukaemia (CLL) with watch and wait status and 21 healthy volunteers. In comparison with the healthy volunteers, where serological response was achieved by 100% subjects, patients on B-cell-targeting therapy (Ibrutinib and Rituximab) had their response dramatically impaired. The serological response was achieved in 0% of Rituximab treated, 18% of Ibrutinib treated and 50% of untreated CLL patients. Cell-mediated immunity analysed by the whole blood Interferon-γ Release immune Assay developed in 80% of healthy controls, 62% of Rituximab treated, 75% of Ibrutinib treated and 55% of untreated CLL patients. The probability of cell-mediated immune response development negatively correlates with disease burden mainly in CLL patients. Our study shows that even though the serological response to SARS-CoV-2 vaccine is severely impaired in patients treated with B-cell-targeting therapy, the majority of these patients develop sufficient cell-mediated immunity. The vaccination of these patients therefore might be meaningful in terms of protection against SARS-CoV-2 infection.

Cellular and humoral immune response to SARS-CoV-2 mRNA vaccines in patients treated with either Ibrutinib or Rituximab

Clinical and Experimental Medicine March 29, 2022

link.springer.com/article/1...

The abstract states that "the majority of these patients develop sufficient cell-mediated immunity" but does not actually define "sufficient immunity". The text of the paper only reports a "positive" or a "negative" cellular response, without defining a "sufficient" cellular response.

Although this is a small study, it is good news for many of us.

gardening-girl

[kitchengardener2]

This is a very interesting report. I am reading and thinking that similar results would be shown for other target treatment such as Acalabrutinib. My husband and I have taken part in the testing project run by the National Office of Statistics, each month we have done a PCR test and a finger prick blood test. Each month our PCR 's have been negative, we would expect this after socially distancing and shielding. Our blood tests showed that my husband (not CLL) was positive for antibodies from after his first covid vaccination. Mine were always negative until after my 4th vaccination when they were inconclusive! I began treatment with Acalabrutinib in August 2021. After reading your post I just wonder (hope) that there may be some antibodies there but not enough to register as positive. Would be interested in other views. We are still being extremely careful, still socially distancing and wearing our masks in shops and when we feel threatened by groups of people. I am hopeful of a 5th and even the possibility of an Autumn 6th vaccination. We are thinking that with care we might be able to take our winter holidays next winter.

[gardening-girl in reply to kitchengardener2]

I would expect the results to be similar for acalabrutinib because it targets the same BTK as ibrutinib, so you may very well have developed a T-cell response to vaccination.

[kitchengardener2 in reply to gardening-girl]

Oh I hope so 🤞🤞

[Psmithuk]

Thank you for this, but I’m wondering whether there are any tests for those on Venetoclax - does it have the same results?Chrisx

[gardening-girl in reply to Psmithuk]

Psmith, this is a quote from the paper below looking at humoral responses to vaccination. Unfortunately it did not mention cellular/T-cell responses.

"CLL patients who received venetoclax monotherapy achieved a significantly higher response rate to anti–COVID-19 vaccines compared with those who received BTKi."

Humoral response to mRNA anti–COVID-19 vaccines BNT162b2 and mRNA-1273 in patients with chronic lymphocytic leukemia

doi.org/10.1182/bloodadvanc...

[bennevisplace]

Thanks for this gardening-girl. It's very welcome, as there seems to be a dearth of publications on cellular responses to vaccine in CLL/ blood cancer patients, even though several studies started soon after the first round of vaccinations in the USA and Europe.

As you flagged, it would have been nice if the authors had defined "sufficient immunity". Perhaps they just mean IFNG IU/ml values comparable with those seen in healthy volunteers, per Fig. 1?

It's not clear to me whether they accounted for background IFNG level, as in ncbi.nlm.nih.gov/pmc/articl...

Interesting finding: "The proportion of responding patients is slightly higher in the Ibrutinib group suggesting that Ibrutinib can overcome the negative impact of CLL on the cellular immunity. It has indeed been shown that Ibrutinib restores T-cell number and function in CLL patients by various mechanisms including targeting of ITK, PD-1 or CTLA-4. [24, 34]" but also that the IGRA value for CLL patients treated with Rituximab was a bit higher than for untreated CLL patients. I didn't expect that!

Fig. 1

[Emgeegee]

Great news! I also heard about a vaccine in testing that is specifically intended to create a very good T cell response, rather than focusing on antibodies, which the developers hope will be potentially very helpful for those immunocompromised people who can’t create antibodies. I don’t know if testing will include the effects of other drugs or not. It is called CoVac-1 and it is German I believe. I don’t suppose anyone has any up to date information? I couldn’t find it mentioned in previous posts.

[gardening-girl in reply to Emgeegee]

CoVac-1 does look quite promising based on results from clinical trial NCT04546841, published in Nature 27 January 2022

A COVID-19 peptide vaccine for the induction of SARS-CoV-2 T cell immunity

ncbi.nlm.nih.gov/pmc/articl...

CoVac-1-induced IFNγ T cell responses persisted in the follow-up analyses and surpassed those detected after SARS-CoV-2 infection as well as after vaccination with approved vaccines. Furthermore, vaccine-induced T cell responses were unaffected by current SARS-CoV-2 variants of concern. Together, CoVac-1 showed a favourable safety profile and induced broad, potent and variant of concern-independent T cell responses, supporting the presently ongoing evaluation in a phase II trial for patients with B cell or antibody deficiency.

I believe that the clinical trial below is the trial referred to in the above publication. It is a trial some of us might be eligible for:

B-pVAC-SARS-CoV-2: Study to Prevent COVID-19 Infection in Adults With Bcell/ Antibody Deficiency (B-pVAC) Interventional Treatment with CoVAC-1

NCT04954469 clinicaltrials.gov/ct2/show...

Inclusion Criteria among others:

Primary antibody deficiency syndrome or Secondary antibody deficiency syndrome, defined by one of the following:

--IgG < 4 g/l

--Ongoing substitution of immunoglobline for hypogammaglobinemia

--Anti-CD20 antibody (monospecific) therapy for malignant disease: after combined Anti-CD20 antibody therapy with chemotherapy (e.g. fludarabin, cyclophosphamid, bendamustin, anthracycline, vincristin) or BTK-inhibitors or BCL2-inhibitors (within 1-6 months post therapy)

--ongoing single agent Anti-CD20 antibody therapy

--Anti-CD20 antibody maintenance therapy

Exclusion criteria among others:

Patient receiving active treatment with small molecules, including Tyrosine Kinases-Inhibitors (e.g. Ibrutinib), Proteosome-Inhibitors (e.g. Bortezomib), Bcl-2- Inhibitors (e.g. Venetoclax), Phosphoinositid-3-Kinase- Inhibors (e.g. Idelalisib)

Thanks Emgeegee, for introducing me to CoVac-1. Unfortunately I am not eligible for this trial because I am being treated with ibrutinib.

[Emgeegee in reply to gardening-girl]

Thanks so much for this information gardening-girl! It’s a pity that they are excluding those of us currently on Btk inhibitors, knowing our poor response shown on antibody tests after covid 19 vaccines. Regardless, this is very interesting - much appreciated!