Obviously we are in a pandemic right now and COVID has definitely changed how we manage healthcare. But fortunately we do have excellent vaccines that have high rates of efficacy in the general population. But we also know that patients with haematological malignancies don’t respond as well to the vaccines. In particular, myeloproliferative neoplasms, or NPNs, are a rare and heterogeneous group of haematological malignant indications that are known to have immune dysregulation and unclear responses to vaccines. So the purpose of the study that we did was to really understand the immune responses that NPN patients specifically have after receiving the Pfizer and Moderna vaccines against SARS-CoV-2.
What was the methodology used in this study?
We were interested in looking at serologic responses one month after completing the vaccine which is the traditional measurement of immunologic responses against vaccines. But we were also interested in looking at T-cell responses because there has been a lot of data indicating that T-cell response is an important aspect of protection after vaccination. So we looked at total IgG, IgM antibody against the SARS-CoV-2 spike protein using a qualitative analyser one month after finishing the vaccine. We also looked at T-cell responses using interferon-gamma release assays. We used two different assays, one is an ELISPOT assay, where you actually look at the number of activated SARS-CoV-2 specific T-cells that you count in these different wells, and then we also looked at interferon-gamma released in the plasma using a whole blood assay. We looked at these responses in 28 NPN patients one month after they received both doses of either the Pfizer or the Moderna vaccine series. We also had a group of healthy controls; I think we had 26 healthy controls. So we compared the serologic responses and then the T-cell responses in these two groups using these assays.
What were your findings?
We found that NPN patients did have very good responses. In terms of the serologic responses we had a 96% seroconverting rate which was the same, actually, as what we saw in the healthy control group. We also saw in the T-cell responses on the ELISPOT assay we found that NPN patients also had high response rates, it was 93% T-cell response rate on this assay compared to 100% within the healthy donors.
But even though NPN patients demonstrated very good responses, we detected that there’s likely at least some subtle deficiencies in cellular immunity that are present. So when you actually look at the magnitude of the T-cell responses on the ELISPOT assay we did see that NPN patients had lower magnitude responses compared to the healthy donors although it’s a little bit unclear if a lower magnitude response, even with a good threshold response, would correspond to any differences in how well protected you are after the vaccine.
We also noticed that there was a discordance between the T-cell responses in the whole blood assay and the ELISPOT assay. So whereas the healthy control was 100% of all participants had a T-cell response on both assays, within the NPN patients only 54% of the patients had a response on the whole blood assay despite having 93% response rates on the ELISPOT assay. So this likely indicated some subtle deficiencies in cellular immunity that the ELISPOT assay is not picking up and that is something that we will have to investigate further.
How can these results impact the future treatment of myeloproliferative neoplasm?
These results give us a lot of information about, one, how NPN patients respond to vaccines and that gives us insight and recommendations for boosters or how patients should behave after they receive their vaccine. A lot of the results are encouraging because we could see high response rates serologically in the ELISPOT assay. But I also do think that NPN patients do have an element of immunocompromise and our results were most salient in the myelofibrosis patients. They might be driving down a lot of the response rates that we see.
So I think that our data supports recommendations for getting booster vaccines, which is generally recommended in all cancer patients in official guidelines. Even after receiving the vaccine we don’t know yet what the effectiveness is in this population so certainly patients should still exercise all the guidelines – wearing masks and washing their hands and avoiding sick contacts etc.
Also, trying to investigate some of these differences in cellular immunity that we might see after vaccination might also give insight in how NPN patients have abnormal immune systems in general and maybe how immunotherapies might have some application in these patients to actually treat their diseases. So certainly a lot more will need to be studied to understand the immune systems of these patients.
Is there anything else that you would like to mention?
Thank you so much for the opportunity to talk to you about the study that we did. Certainly we are continuing to study this cohort; we’re looking at longer term responses after the vaccine and looking at responses after the booster and also trying to use different immune profiling techniques to better understand why we’re seeing lower magnitude responses or discrepancies between assays in this initial study.