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Leukemia

Vaccines Won’t Protect Millions of Patients With Weakened Immune Systems

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For more than a year, Dr. Andrew Wollowitz has mostly been cloistered inside his home in Mamaroneck, N.Y.

As chief of emergency medicine at Montefiore Medical Center in the Bronx, Dr. Wollowitz, 63, was eager to help treat patients when the coronavirus began raging through the city last spring. But a cancer treatment in 2019 had obliterated his immune cells, leaving him defenseless against the virus, so he instead arranged to manage his staff via Zoom.

A year later, people in Dr. Wollowitz’s life are returning to some semblance of normalcy. His wife, a dancer and choreographer, is preparing to travel for work at Austria’s National Ballet Company. His vaccinated friends are getting together, but he sees them only when the weather is nice enough to sit in his backyard. “I spend very little time in public areas,” he said.

Like his friends, Dr. Wollowitz was vaccinated in January. But he did not produce any antibodies in response — nor did he expect to. He is one of millions of Americans who are immunocompromised, whose bodies cannot learn to deploy immune fighters against the virus.

as high as 55 percent.

Most people who have lived with immune deficiencies for a long time are likely to be aware of their vulnerability. But others have no idea that medications may have put them at risk.

“They’ll be walking around outside thinking they’re protected — but maybe they’re not,” said Dr. Lee Greenberger, chief scientific officer of the Leukemia and Lymphoma Society, which funds research on blood cancers.

The only recourse for these patients — apart from sheltering in place until the virus has retreated — may be to receive regular infusions of monoclonal antibodies, which are mass-produced copies of antibodies obtained from people who have recovered from Covid-19. The Food and Drug Administration has authorized several monoclonal antibody treatments for Covid-19, but now some are also being tested to prevent infections.

Convalescent plasma or gamma globulin — antibodies distilled from the blood of healthy donors — may also help immunocompromised people, although a version of the latter that includes antibodies to the coronavirus is still months from availability.

compassionate use program. (Regeneron released trial results this week showing that the cocktail reduces symptomatic infections by 81 percent in people with normal immune systems.)

It’s unclear how many immunocompromised people don’t respond to coronavirus vaccines. But the list seems at least to include survivors of blood cancers, organ transplant recipients, and anyone who takes the widely used drug Rituxan, or the cancer drugs Gazyva or Imbruvica — all of which kill or block B cells, the immune cells that churn out antibodies — or Remicade, a popular drug for treating inflammatory bowel disease. It may also include some people over age 80 whose immune responses have faltered with age.

“We’re extremely concerned and interested in trying to see how we might be able to help those particular patients,” said Dr. Elad Sharon, an immunotherapy expert at the National Cancer Institute.

As the pandemic spread, doctors who specialize in treating blood cancers or who care for immunocompromised people expected at least some of their patients to encounter difficulties. Dr. Charlotte Cunningham-Rundles, an immunologist at Icahn School of Medicine at Mount Sinai in New York, has about 600 patients who are almost entirely dependent on getting regular doses of gamma globulin to stay safe from pathogens.

Even so, 44 of her patients became infected with the coronavirus; four died, and another four or five had long-term illnesses. (Chronic infections may offer opportunities for the virus to evolve into dangerous variants.)

registry to provide information and antibody tests to people with blood cancers. And several studies are assessing the response to coronavirus vaccines in people with cancer, autoimmune conditions like lupus or rheumatoid arthritis, or who take drugs that mute the immune response.

In one such study, British researchers followed nearly 7,000 people with Crohn’s disease or ulcerative colitis from 90 hospitals in the country. They found that less than half of patients who took Remicade mounted an immune response following coronavirus infection.

were protected after a single dose of the Pfizer vaccine and only 27 percent after a single dose of the AstraZeneca vaccine. (In Britain, the current practice is to delay second doses to stretch vaccine availability.)

Likewise, another study published last month indicated that fewer than 15 percent of patients with cancers of blood or the immune system, and fewer than 40 percent of those with solid tumors, produced antibodies after receiving a single dose of the Pfizer-BioNTech vaccine.

And a study published last month in the journal JAMA reported that only 17 percent of 436 transplant recipients who got one dose of the Pfizer-BioNTech or Moderna vaccine had detectable antibodies three weeks later.

Despite the low odds, immunocompromised people should still get the vaccines because they may produce some immune cells that are protective, even antibodies in a subset of patients.

“These patients should probably be prioritized for optimally timed two doses,” said Dr. Tariq Ahmad, a gastroenterologist at the Royal Devon and Exeter NHS Foundation Trust who was involved in the infliximab studies.

He suggested that clinicians routinely measure antibody responses in immunocompromised people even after two vaccine doses, so as to identify those who also may need monoclonal antibodies to prevent infection or a third dose of the vaccines.

Wendy Halperin, 54, was diagnosed at age 28 with a condition called common variable immunodeficiency. She was hospitalized with Covid-19 in January and remained there for 15 days. But the coronavirus induced unusual symptoms.

“I was having trouble walking,” she recalled. “I just lost control of my limbs, like I couldn’t walk down the street.”

Because she was treated for Covid-19 with convalescent plasma, Ms. Halperin has had to wait three months to be immunized and has made an appointment for April 26. But despite her condition, her body did manage to produce some antibodies to the initial infection.

“The take home message is that everybody should try and get the vaccine,” said Dr. Amit Verma, an oncologist at Montefiore Medical Center.

The gamble did not pay off in Dr. Wollowitz’s case. Without antibodies in his system to protect him, he is still working from home — a privilege he is grateful for. He was an avid mountain biker and advanced skier, both of which carry risk of injury, but with the coronavirus, he is playing it safe.

In anticipation of returning to his normal lifestyle, Dr. Wollowitz is tuning his bicycles. But he said he foresaw himself living this way till enough other people are vaccinated and the number of infections in the city drops.

“I’m not exactly sure what that date is,” he said. “I’m really waiting to get back out.”

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Sickle Cell Treatment Not Linked to Cancer, Researchers Say

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Just a few weeks after a promising gene therapy for sickle cell disease seemed to have hit a roadblock, prospects for the treatment now look better. Preliminary data suggesting that it might cause cancer have not held up.

In the gene therapy, scientists insert a normal gene into patients’ DNA to help correct sickle cell disease, which is caused by a devastating mutation. The cutting-edge treatment may prove to be a cure, and a company that is testing the treatment, Bluebird Bio, had been on track to apply to the Food and Drug Administration for approval next year.

But on Feb. 16, Bluebird Bio announced that a sickle cell patient treated five years ago in a clinical trial had developed acute myeloid leukemia. Another patient got acute myelodysplastic syndrome, a form of cancer that is often a precursor to leukemia.

The company shut down its trials for sickle cell patients and those with another blood disorder, beta thalassemia, while its researchers sought to understand if the gene therapy was at fault.

On Wednesday, Bluebird Bio reported that it had not found evidence that the gene therapy caused the sickle cell patient’s leukemia.

The gene inserted in the patient’s DNA did not disrupt the functioning of other genes, the company said. And the gene was not inserted near any others in the genome known to be involved in leukemia.

Bluebird Bio is still investigating whether its treatment may be linked to acute myelodysplastic syndrome, but officials have asked the Food and Drug Administration to allow its clinical trials to continue.

A separate sickle cell trial, at Boston Children’s Hospital, was also shut down when Bluebird Bio announced the two cancers at the request of the National Institutes of Health, which is paying for the trial.

Dr. David Williams, a hematologist at Boston Children’s and a principal investigator of the trial, said the researchers are asking the N.I.H. for permission to resume their work.

Like Bluebird Bio’s investigators, Dr. Williams and his colleagues are using a disabled lentivirus to deliver a gene to sickle cell patients. Lentiviruses are thought to be safe — hundreds of patients in other gene therapy trials have been treated with them, and no blood cancers were reported. The possibility that lentiviruses might not be safe was of grave concern.

The leukemia patient in the Bluebird Bio trial carried genetic abnormalities associated with leukemia, which could explain why it developed.

Philip Gregory, chief scientific officer at the company, said it is not yet clear if the patient diagnosed with myelodysplastic syndrome actually has it. So far, Bluebird Bio has not been able to find any cancer cells in his bone marrow.

“He may have been prematurely diagnosed,” Dr. Gregory said. If cancer cells are found in the patient’s marrow, Dr. Gregory added, the company will proceed with the same detailed molecular analysis it did for the leukemia patient.

Dr. John Tisdale, chief of the cellular and molecular therapeutics branch at the National Heart, Lung and Blood Institute, was cautiously optimistic.

“These data indeed point away from the vector as causative,” he wrote in an email. But, he added, researchers still need to better understand the illnesses in the trial participants before they can breathe a final sigh of relief.

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