Do Patients With Cancer Need a Third Shot of COVID Vaccine?
Patients with cancer have shown varying responses to COVID-19 vaccination, with good responses in patients with solid tumors (even while on systemic therapy), and poor responses in patients with blood cancers, particularly those on immunosuppressive therapies.
The data are evolving to show factors associated with a poor response, but are not strong enough yet to recommend booster shots, say researchers.
The work is defining who will likely need a COVID vaccine booster when they become available. “It’s definitely not all cancer patients,” said Dimpy Shah, MD, PhD, a cancer epidemiologist at the Mays Cancer Center, University of Texas, San Antonio.
Public Anxiously Awaiting Boosters
Boosters aren’t recommended in the United States at the moment, in large part because the Emergency Use Authorization under which the vaccines are being administered allows for only two shots of the Pfizer and Moderna vaccines and one shot of the Johnson and Johnson vaccine.
Even so, regulators and policymakers are “keenly aware that physicians and patients alike are anxious to get going and start doing boosters,” Shah said. There’s concern that antibody response might wane over time, and perhaps even more quickly in patients with cancer.
Pfizer is already in talks with the US Food and Drug Administration to authorize a third dose of its vaccine in the United States. Guidelines could very well change in coming months, said Ghady Haidar, MD, a specialist in infectious diseases and cancer at the University of Pittsburgh, Pittsburgh, Pennsylvania.
However, it’s still early in the game and it’s not clear yet if boosters are necessary in cancer, Haidar told Medscape Medical News.
For one thing, it’s unknown if poor antibody response really means that patients aren’t protected, he explained. The vaccines elicit T-cell responses that could protect patients regardless of antibody levels. It’s also unclear if antibody titer levels are clinically relevant, and there hasn’t been much indication yet that less-than-robust vaccine responses translate to worse COVID outcomes in patients with cancer.
Those and other questions are areas of active investigation by Shah, Haidar, and others. Dozens of clinical trials are investigating vaccine response in patients with cancer, including the use of boosters.
Meanwhile, some cancer patients aren’t waiting around for more study results. “I get many, many emails a day” about booster shots, Haidar said. “We recommend against” them for now but some people bend the rules and get an extra shot anyway. “I get it. People are apprehensive.”
Three COVID Deaths Despite Full Vaccination
The vaccine clinical trials had fewer patients with cancer, so researchers are moving fast to backfill the data. Although there is some variation in what’s being reported, an overall picture is slowly emerging.
Shah and her team reported on responses to the mRNA COVID vaccines from Pfizer and Moderna, and found a 94% seroconversion rate in 131 patients with cancer 3-4 weeks after their second dose of vaccine. They also found good responses among patients on cytotoxic chemotherapy within 6 months of their first vaccine dose, although their antibody titer levels were significantly lower than seen in other patients with cancer.
Investigators from Montefiore Medical Center in New York City also recently reported a 94% seroconversion rate among 200 patients with cancer, including 98% seroconversion in patients with solid tumors. Rates were lower in patients with blood cancers, but were still 85% overall, with 70% conversion among patients on anti-CD20 therapies and 73% among stem cell transplant patients.
Haidar’s group reported a seroconversion rate of 82.4% among patients with solid tumors but only 54.7% among those with blood cancer. Risk factors for poor response included treatment with antimetabolites and anti-CD20 therapies, and, in the solid tumor group, radiation therapy, likely because of its overall toxicity and impact on lymphocyte function.
Israeli investigators reported in May a 90% seroconversion rate after two doses of the Pfizer vaccine among 102 patients with solid tumors on active treatment, which compared favorably to the 100% conversion rate in healthy controls, but they noted that antibody titers were considerably lower in patients with cancer.
The only variable associated with lower titer levels was combined use of chemotherapy and immunotherapy, they noted. There were also three women on dose-dense chemotherapy for breast cancer who did not produce any antibodies.
In a study limited to patients with blood cancers, a Lithuanian team recently reported that among 885 patients, those on Bruton tyrosine kinase inhibitors, ruxolitinib (Jakafi), venetoclax (Venclexta), or anti-CD20 therapies mounted almost no antibody response to the Pfizer vaccine.
The Lithuanian group also reported nine breakthrough COVID infections among their fully vaccinated blood cancer patients, including three deaths.
A team from the Icahn School of Medicine in New York City reported that more than 15% of 260 patients with multiple myeloma also had no response to the Pfizer or Moderna vaccine; they were on BCMA-targeted therapy or anti-CD38 monoclonal antibody therapy at the time of vaccination, but a few had undergone CAR-T cell therapy more than 3 months beforehand.
Heated Debate About Antibody Testing
Despite these reports of some patients with cancer having poorer responses, there’s some uncertainty over the benefit of giving a third (booster) shot.
There’s the question about the clinical relevance of antibody titer levels, and very little work has been done to date on cellular T-cell immunity from the vaccines.
“Right now, we are using titer levels like they actually mean something when they might not,” said Ravi Parikh, MD, a genitourinary and thoracic oncologist at the University of Pennsylvania, Philadelphia, who co-wrote an editorial that accompanies the Israeli report.
That’s one of the reasons why the FDA and others do not currently recommend antibody tests for COVID vaccine decisions outside of a clinical trial, but not everyone agrees with that position.
There’s been “a lot of heated debate in the medical community” over the issue, Haidar said.
The Icahn team, for instance, said that their results “underscore the need for routine serological monitoring of [multiple myeloma] patients following COVID-19 vaccination” to see if they might still need to mask-up and socially distance.
There is precedence, too, for vaccine boosters in cancer. As Parikh noted in his editorial, guidelines recommend revaccination after stem cell transplant for meningococcus, tetanus, and varicella, and other infections.
Already in France, COVID booster shots are standard care for patients on dialysis and those on anti-CD20 agents, as well as for solid organ transplant recipients, for whom the literature supporting the benefit of COVID boosters is much more evolved than in cancer.
Israel has also authorized vaccine boosters for immunocompromised patients, including those with cancer, according to news reports.
It is also almost certain that the FDA will grant a formal approval for the COVID vaccines, at which point doctors will be free to administer boosters as they see fit.
“People are going to have to think really hard about what to do with them” if guidance hasn’t changed by then, Haidar said.
As the story unfolds, Haidar and others told Medscape Medical News that the take-home message for oncologists remains largely what it has been — namely to get patients vaccinated, but also to consider masks and social distancing afterward for those at risk of a poor response.
Shah, Haidar, and Parikh have disclosed no relevant financial relationships. Parikh is a regular contributor to Medscape Oncology.
M. Alexander Otto is a physician assistant with a master’s degree in medical science, and an award-winning medical journalist who has worked for several major news outlets before joining Medscape. He is an MIT Knight Science Journalism fellow. Email: [email protected]
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