MPNforum Magazine

The illusion and reality of immunity.

-Zhenya Senyak

I was vaccinated at the local VA hospital.  Twice.  The second time they handed me proof, a COVID 19 vaccination card. I expected some of the anticipated reported symptoms — headache, brief loss of smell, fatigue, confusion.  Nothing.

A little soreness at the injection site. And a sense of elation. I dodged a bullet. 13 months surrounded by an invisible lethal virus and now I was immune. Shielded by science with a stamped vaccine passport to show for it.

Not so fast. Those symptoms I never felt?  They would have been the echoes of my immune system stamping out the imitation CoVID virus cooked up in the Moderna labs.

As an MF patient with a severely compromised immune system chances are not much of an uproar happened after the jab.  You need a functioning robust set of cells — neutophils, B Cells, T-Cells, plasma capable of churning out antibodies, Killer Cells, phagocytes, lymphocytes etc. along with intact organs — to build immunity.  Once the MRNA virus is presented to the blood stream, the antibody generating system swings into action, identifying and attacking the intruder.

Unless your antibody generating system is weakened. And T cells are sidelined.

The evidence is building that patients suffering from hematologic malignancies cannot expect a  flood of antigens, antibodies to follow from Covid vaccination…or flu or any vax for that matter.  The somewhat good news is we don;t actually know how strong a response is necessary to mitigate the effects of Covid 19 infection.  And we likely have enough of a vaccine response to help us avoid hospitalization, ventilators and the rest after infection..  But the research hasn’t yet been done.

This is not a one size fits all scenario. Immune response is a complicated issue depending on medications being taken, clinical condition, timing, genetics…. But MPN patients need to be aware of the dangers, “… blood cancers such as leukemia and lymphoma,” reports Science magazine, “can themselves deplete or disrupt certain type of immune cells.”

We measured SARS-CoV-2 IgG (antibodies) production in 67 hematology malignancy patients who received 2 mRNA vaccine (Pfizer/BioNTech or Moderna)  doses. We found that 46% of HM patients did not produce antibodies and were therefore vaccine non-responders.

https://www.medrxiv.org/content/10.1101/2021.04.06.21254949v1 (Cold Springs Harbor Lab)

Who’s at risk..

MPN is a hematologic malignancy. So to some extent all of us who have been vaccinated are at risk of falsely believing ourselves safe from Covid 19 infection or serious illness after infection. The risk is greatest in patients undergoing chemotherapy, recovering from stem cell transplant, and those of us in  a severely compromised state due to immunosuppressive drugs.

Does Jakafi compromise our immune system?

Jakafi’s ability to reduce pro-inflammatory cytokines, shrink swollen spleen, improve symptoms and quality of life comes at a cost.  “At the same time, the anti-cytokine action could potentially cause an immunosuppressive effect of the drug, since the immune system and the hematopoietic system share intracellular signaling pathways, mediated by common receptors for cytokines and growth factors which, by acting on the JAK-STAT pathway, are important for the proliferation, differentiation, and activation of cells involved in innate and adaptive immune responses.

“With growing clinical experience, concerns about infectious complications, and increased risk of B-cell lymphoma, presumably caused by the effects of JAK1/2 inhibition on immune response and immunosurveillance, have been raised

“Evidence shows that ruxolitinib exerts potent anti-inflammatory and immunosuppressive effects. Cellular targets of ruxolitinib include various components of both the innate and adaptive immune system, such as natural killer cells, dendritic cells, T helper, and regulatory T cells. “
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854013/

Because of this limited protection, doctors generally advise that immuno-compromised patients continue to adhere strictly to other preventive measures, such as limiting their time in crowds, regular hand washing, mask wearing, and social distancing.

“Get vaccinated, but behave as though you’re not,” Dr. Dorlan Kimbrough, a neurologist at Duke University.

Another piece of evidence was revealed in  the preliminary results of the SOAP study from King’s and the Francis Crick Institute. The anti-SARS-CoV-2 antibody responses at week three following the first dose of the vaccine were only 39% in the solid and 13% in the haematological cancers, compared to 97% in those without cancer.

“The study…also reports that when the second dose of the vaccine was given three weeks after the first dose, the immune response improved significantly for solid cancer patients with 95% of them showing detectable antibodies to the SARS-CoV-2 virus within just two weeks. By contrast, those who did not get a vaccine boost at three weeks did not see any real improvement, with only 43% of solid cancer patients and 8% of blood cancer patients developing antibodies to the Pfizer vaccine at five weeks compared to 100% of healthy controls.”
https://www.crick.ac.uk/news/2021-03-11_delaying-second-pfizer-biontech-dose-could-leave-cancer-patients-with-insufficient-immunity

The medical consensus: We should all get vaccinated, compromised immune system or not,  as soon as medically possible. Those of us in the midst of stem cell transplant need to talk with our hematologist and transplant team. .  And, for now at least, we can’t go wrong following Dr. Kimbrough;s advice: Act in enclosed public spaces as if we weren’t vaccinated: Mask, Social distance, Handwashing.

For confirmation,  we turned to three noted and deeply experienced friends of the MPN community, Dr. Claire Harrison , Dr. Ruben Mesa and Dr. Richard T. Silver to get their readings on the pandemic, vaccine and MPN.

A ray of hope from Professor Claire Harrison, Clinical Director — Guy’s and St. Thomas’ NHS Foundation Trust.

“No vaccine is perfect but the available COVID vaccines are pretty good far better for example than annual influenza vaccination and regarding MPN and flu vaccine we recently published -Aliman et al BJH that Immune responses to annual influenza vaccine are seemingly different in some MPN patients)

It is important to understand that at present we do not know what level of antibody, T or B cell response to a COVID vaccine is equivalent to robust immunity

“Concerning COVID vaccines.  The SOAP study attracting a lot of press and causing consternation which came from our institution did not include a single MPN patient mostly the haematology patients were those with B cell (ie antibody producing cell) diseases on treatments directed at suppressing B cells.

Our team – talented PhD student Patrick Harrington supervised by Hugues de Lavallade, Donal McLornan and myself have shortly to be published data from a study we have swiftly completed supported by a grant from MPN Voice and Blood Cancer UK  suggesting that the majority of MPN patients have what we think is are pretty normal antibody responses.

Our Guys and St Thomas/MPN Voice data also includes detailed T and B cell analysess. Due to complexity of tests and difficulty capturing patients pre and post the rapid vaccine roll out we did not yet include sufficient MF and ruxolitinib treated MF patients to draw firm conclusions. We are currently expanding the cohort and following patients longitudinally. If there are UK patients treated at Guys or locally watch out for a message from MPN Voice inviting participants

“International advice is even if you are fully vaccinated you are still not 100% protected and dependent on the local infection scenario currently you would still need to observe national or regionally imposed precautions lockdown, masks etc”

And, an equally promising observation from Dr. Ruben Mesa, Professor of Medicine and Executive Director of the Mays Cancer Center at UT Health, San Antonio, MD Anderson:

“Response to the vaccine can include but B cell mediated (i.e. humoral) and measurable by antibodies and T cell (which might still be present even if antibody titer is low). We still suspect patients with hematological malignancies with low antibody titers post vaccination likely still have some protection (some protection might lead to no COVID19 infection or perhaps a less severe case of COVID19 if acquired).

Amongst patients with Hematological Malignancies those with B cell disorders (CLL, Lymphoma, Mantle Cell Lymphoma) who have received complex chemotherapy including rituximab probably have the lowest antibody response to vaccine. In unpublished data I have seen across a large group of post vaccinated HM patients those WITHOUT an antibody response ranged from 45% with no response (Mantle Cell Lymphoma and Advanced CLL) to 0% patients without response (MPN! And MDS).

So I think the vast majority of MPN patients probably respond to vaccine and likely have anywhere from partial to full response. It is an evolving science but there probably is a big differences amongst the HM that might favor MPNs.”

With a note of caution from Dr. Richard T. Silver, professor of medicine and the emeritus director of the Richard T. Silver M.D. Myeloproliferative Neoplasms Center at Weill Cornell Medicine.

Agree with excellent notes of Claire and Ruben.

We have had at our institution two COVID deaths in immunized  CLL patients receiving  ibrutininb, presumably  reflecting impaired B cell response.

Also one MDS patient   I was   somewhat surprised by this because antibody  studies years ago we did in acute myeloid leukemia showed no impaired antibody  response  to “B cell-like antigens”  The MDS patient had received a good deal of chemotherapy.  No deaths in immunized MPN patients  from COVID  as yet, but they have been extremely careful maintain  masks, exposure , etc.  regardless of receiving vaccination.Our local advice is to be chary about mask removal and exposure ……..the old adage safe/sorry applies.