‘It’s not over yet’: Uncertain protection from Covid vaccines leaves cancer patients in limbo

After 14 long months of near-isolation, Michele Nadeem-Baker was ready for her Covid-19 vaccination. Diagnosed with chronic lymphocytic leukemia in 2012, she knew her cancer made her more vulnerable to severe illness should she become infected with Covid-19. She would leave her home in Charlestown, Mass., only to walk her chocolate lab, Gabby, with her husband, dreaming of a day when she would no longer need to keep her distance from other family and friends.

She’s fully vaccinated now, but Nadeem-Baker feels left behind by the vaccine euphoria sweeping the country as it resumes something like normal life. She has only trace amounts of antibodies to show for her two doses of Moderna’s vaccine, according to test results from a study she joined, and that puts her in limbo — uncertain how much protection she has against the virus.

“With everyone else in the country, I was very excited about the vaccine and hoping I would be able to rejoin society. And unfortunately, that’s not able to happen and that was a huge disappointment,” she said. “It’s not over yet for patients like me.” 

advertisement

Her cancer and the treatment she takes to control it blunt her immune system to the point that it doesn’t churn out as many antibodies as the vaccines are designed to stimulate. People who take drugs to prevent rejection of their organ transplants face a similar dismay after vaccination, as do people with certain autoimmune diseases who take medications to dampen the overactive immune response that defines their disorder.

The new Covid-19 vaccines, developed with astonishing speed and marked by stunningly high efficacy, may not work for everyone. But the jury is still out on whether antibody tests are a definitive measure of protection, for two reasons: We still don’t know the minimum level of antibodies required to fend off SARS-Cov-2 in immunocompromised people, nor do we know whether another response, known as cellular immunity, might make up the difference. It’s also too soon to determine if booster shots or monoclonal antibody infusions would help.

advertisement

Just hold on, experts told STAT. Like so much in the pandemic, more is being learned every day about the virus. In the meantime, doctors strongly recommend vaccination for immunocompromised people and urge them to mask up, socially distance, and remind people around them to do the same, no matter their vaccination status.

I think we need people to understand this doesn’t mean you have to lock yourself in a room in quarantine, but it does mean that you should exercise caution because we do not know how much antibody you need,” said Gwen Nichols, an oncologist and chief medical officer of the Leukemia and Lymphoma Society. “We don’t know all the specifics, but there are people taking what look like identical regimens and one of them has a completely normal serology and the other doesn’t, so we believe there may be something else. We know there were individual factors with Covid. It’s not going to be a simple answer.”

Studies to answer those questions are enrolling patients now. The antibody test Nadeem-Baker took is offered to patients by the Leukemia and Lymphoma Society to learn exactly what factors might influence whether vaccines work for people with blood cancer. Patients began signing up in February for an analysis that will look at variables such as their disease, their age, their therapies in the last two years, and whether they stopped treatment before vaccination. 

At this point, the Centers for Disease Control and Prevention does not recommend antibody tests to gauge vaccine response. While the tests are useful on a population level to determine the burden of Covid-19, doctors don’t know how to interpret them for this purpose — yet. 

“It’s just because we have less than one year of experience, it’s hard to know how much or how well the vaccines protect, depending on the specifics of immunocompromise in the patient. It may be that in three months we’ll be using these tests regularly,” said Meghan Baker, an infectious diseases physician and hospital epidemiologist who works with immunocompromised patients at Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston. Meanwhile, she strongly recommends vaccination. “We also know that many of our patients are very vulnerable to SARS-CoV-2 and Covid and can get very sick. And so any protection is strongly recommended.” 

All this leaves people like Greg Simon frustrated. A health policy consultant who led the Biden Cancer Initiative before it closed when the president announced his run for office, he was diagnosed with chronic lymphocytic leukemia in 2014. Simon was disappointed to learn he had no detectable antibodies to SARS-CoV-2 after his two Pfizer vaccine doses. 

“I realize that I’m part of a trend. I’m not an exception, which is too bad,” he said. “I expected that I would get some immunity, but that I would still have to be careful and maybe get a booster. So it did surprise me.” 

Simon even got a third vaccine dose — of the Johnson & Johnson one-shot vaccine — in hopes of spurring a response. And he’s looking into monoclonal antibody treatments such as those developed by Regeneron, AstraZeneca, Bristol Myers, and GlaxoSmithKline, though he knows such treatments have so far been shown to help people only once they’re infected. He’s being extra cautious to ensure he can meet his first grandson, who’s due to be born in July.

“I’m not going to be hanging out in a restaurant anytime soon because the risk-reward ratio is bad,” Simon said. 

He sees another element to the story for not just cancer patients like him, but also people with autoimmune diseases or who have had organ transplants.

“I’m a well-insured white guy, so I can go get these tests every month and it’s covered,” he said. “But not everybody is well-insured and not everybody has access to all the things that some of us have access to. We can share the knowledge we have, which is the lack of protection, even if there’s not a solution.” 

More information is coming on how transplant recipients are responding to Covid vaccination, and the picture is discouraging. Only 15% of the people in a Johns Hopkins study published this month mounted a response to both the first and the second dose of either the Moderna or Pfizer vaccine. It’s well-known that transplant recipients, who take immunosuppressive drugs for the rest of their lives to prevent rejection, don’t respond well to vaccination in general. Like cancer patients, they are also at greater risk of severe illness and death from Covid-19, so even some protection would be beneficial.

Brian Boyarsky, a research fellow and surgeon at Johns Hopkins School of Medicine and a co-author of the study, was surprised by how low the antibody response was. His group is looking into two options: modulating the immunosuppression regimen patients take and adding booster doses to see if they might confer some additional protection, as they do against hepatitis B.

There’s another potential downside for immunocompromised patients, Boyarsky said. “If the vaccines are not working, that could mean that transplant recipients are not only at a higher risk for developing the disease, but also for harboring potentially resistant strains of the virus that could render the vaccine ineffective for everybody.”

For people with autoimmune diseases, in which the body attacks its own tissues in an overactive immune response, the picture is more nuanced than with cancer, where both the disease and many of the treatments knock out the cells involved in the body’s immune response. The therapies to keep autoimmune patients healthy pose the barrier to vaccination. 

Some autoimmune patients take drugs from the same class of antimetabolites as transplant patients use. “From an antibody standpoint, clearly they are not going to make a good response,” said Ignacio Sanz, who heads rheumatology at Emory School of Medicine. He is leading a study of Covid-19 vaccine responses in people with autoimmune diseases.

Unlike cancer or transplant patients, people with some autoimmune diseases might be able to pause treatment until vaccine-induced antibodies translate into immune memory cells, he suggested.

“Unless there’s some major clinical concern that the disease is active, I’d rather wait one or two months for the next treatment, which I think is perfectly fine in most cases,” he said. “It depends on the individual case, obviously, but if I think that the patient can afford to wait a couple of months, I’d rather vaccinate and then delay that particular therapy for a couple of months.”

Like Nichols of the Leukemia and Lymphoma Society and Baker of Dana-Farber, Sanz urges cancer, transplant, and autoimmune disease patients to get vaccinated, and to remain vigilant until more is known about protection against Covid-19.

While she waits for answers, Nadeem-Baker feels like her life is still stagnant. A communications professional, she keeps active in patient advocacy groups such as Patient Power, WEGO Health, and AnCan, spreading the word about Covid vaccination.

“It’s not just leukemia patients,” she said. “This is not over for everyone and there’s still a great danger to many of us.”

Source: STAT