Third Full Dose of COVID-19 Vaccine Increases Antibody Response in Patients with Blood Cancers

After prior data showed that one in four patients with B-cell malignancies did not produce detectable antibodies after receiving their first two doses of the COVID-19 mRNA vaccine, new findings are more promising for these patients.

In results from a larger pool of data presented at the 63rd ASH Annual Meeting, 43% of the patients (109 out of 245) with blood cancers who did not produce antibodies after being administered their first two doses produced antibodies after receiving a third full dose of the mRNA vaccine.

“In addition to that, the balance of the patients from 245 up to 699 — those 454 patients that were making some antibodies before, after the third vaccination made a very large amount of antibodies in general, up to the maximum amount of antibodies that the assay is capable of detecting. So, they are well protected,” said Lee Greenberger, chief scientific officer of the Leukemia & Lymphoma Society (LLS), in an interview with CURE®.

Greenberger also pointed out the important distinction here between a COVID-19 booster and a third dose — the patients with blood cancer in this study received a third full strength vaccination dose of whatever mRNA vaccine is available to them, rather than a booster dose.

In particular, patients with a blood cancer received the 100-microgram dose of the Moderna vaccine and not the 50-microgram dose that non-immunosuppressed individuals received in the general population. Patients with a blood cancer who received the third dose of the Pfizer vaccine received the same strength as the general population.

Why Patients With B-Cell Malignancies Produce Fewer Antibodies

The researchers, whose data was reported from the LLS National Patient Registry, included a larger number of patients with B-cell malignancies in the study to analyze this population specifically due to their challenges in producing antibodies to prior COVID-19 vaccine doses.

The reason that these patients typically do not see a stimulation of anti-spike antibodies — which block entry of COVID-19 into the cells — is because their cancer type or their cancer therapy depletes the immune system’s B-cells, and these cells are responsible for making antibodies that fight viruses.

“So if you don't have a high number of B-cells, or the functionality is suppressed, they won't make antibodies,” Greenberger said. “And therefore, if you give (them) a vaccine, you just don’t make antibodies.”

These types of cancers include chronic lymphocytic leukemia (CLL), and some of the most common non-Hodgkin lymphomas: diffuse large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma, mantle cell lymphoma (MCL) and Waldenström macroglobulinemia.

However, in patients with other types of blood cancers, including myeloid forms of leukemia, Hodgkin lymphoma and multiple myeloma, detectable antibody rates ranged from 75% to 100%. These cancer types also typically respond favorably to the first two doses of COVID-19 vaccines.

Certain Cancer Treatments May Affect Antibody Production

Treatments such as Bruton tyrosine kinase (BTK) inhibitors, CD19 CAR-T cell therapies and anti-CD20 antibody treatments that deplete B-cells may weaken the immune response to the COVID-19 while a patient is on them, or even for several months after therapy is complete.

“There is also a component that the disease itself suppresses B-cell function and that also, even patients who don't have any of those therapies may have impaired B-cell responses and fail to make anti-spike antibodies,” Greenberger said.

Of the 320 patients with CLL in the study who are commonly treated with these therapies, 65% of patients who did not receive therapy for two years prior to receiving the vaccine were able to produce antibodies after the third dose. Conversely, patients in this population who did receive these therapies in the last two years had less chance of benefit, with just 23% to 41% producing antibodies post-third dose.

On the other hand, patients who received a certain type of antibody infusion as part of their cancer treatment may obtain an added benefit with the COVID-19 vaccine. Intravenous immunoglobulin (IVIG) infusion, which is typically given to patients on BTK inhibitors, anti-CD20 antibodies or CAR-T cell treatments to replace the lost antibodies, has an increased level of COVID-19 anti-spike antibodies. The reason for this is that IVIG comes from people who donate blood plasma, and many more of the donors are now either vaccinated or have had COVID-19 and thus their plasma contains antibodies.

The LLS study found that some patients treated with this infusion had unusually high levels of antibodies after receiving the third vaccine dose, even among those who had no antibody production after their first two doses.

Patients Should Continue Protective Strategies, Regardless of Vaccination or Antibody Status

It’s important for patients with blood cancer to know, Greenberger stressed, that the COVID-19 vaccine is safe for them to receive.

“The safety (of the vaccine) is not an issue,” he said. “You may make anti-spike antibodies to the vaccination, so it’s important to get them, including the third vaccination.”

However, getting the vaccine — no matter the dose — should not prevent patients from continuing their preventive strategies against the virus.

“They should mask up, they should observe distance rules,” Greenberger said. “And they need to be careful. Particularly patients who have B-cell malignancies, (they) should consider themselves not fully protected, and be careful.”

Antibody Cocktails May Help Patients After COVID-19 Exposure

For patients who need to be extra careful about their COVID-19 exposure, Greenberger noted that antibody cocktails may be a helpful option.

Three antibody cocktails and one single antibody are useful to prevent or reduce symptoms of COVID-19 infections. The bamlanivimab and etesevimab antibody cocktail, as well as the casirivimab and indevimab antibody cocktail is used to treat mild to moderate COVID-19.

Both cocktails received additional FDA emergency authorization for use in patients who may be at high risk of progression to severe COVID-19 infections (post-exposure prophylaxis).

The single antibody, Xevudy (sotrovimab), is also FDA-authorized for use in the latter indication.

Recently, the tixagevimab and cilgavimab cocktail received FDA emergency authorization for immunocompromised patients that do not have COVID-19 but are at high risk of poor outcomes if they contract COVID-19 (pre-exposure prophylaxis).

The utility of these antibodies against the Omicron variant is currently under investigation and is likely to be very important in those patients who fail to either make any antibodies or sufficient antibodies after three mRNA vaccinations, according to Greenberger.

“In addition, there are studies with fourth vaccinations,” he said. “Remember that the FDA has basically told patients who are immunosuppressed, after they get the third vaccination, six months later, they should get another vaccination — the fourth vaccination, that is an option.”

He added that the LLS registry will be following patients who would like to participate and are eligible to receive their fourth dose.

“And sometimes it's kind of like starting a car that won't want to start,” Greenberger explained. “Well, if you try starting it enough, it will eventually start and turn over. And that's what we're hoping for some of these patients who don't make antibodies.”

Beyond that, patients who are on therapies with long-lasting B-cell suppressive effects will see these effects eventually time out and their B-cells may be able to start responding to vaccinations again.

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